| Study | Country Study period Study design |
Data source | Exposure definition | Non-exposure definition | Exposition period | Sample size (exposed/unexposed) Or (case / control) |
Remarks | Risk of bias |
|---|---|---|---|---|---|---|---|---|
|
Andersen (Controls unexposed, NOS) 2014 |
Denmark 1997 - 2010 population based cohort retrospective |
The Danish administrative health registries and linked through the CPR-number, a unique identification number given to all citizens. | Pregnant women dispensing of a prescription of fluoxetine, citalopram, paroxetine, sertraline or escitalopram (at least the first 35 days of pregnancy). |
unexposed (general population or NOS)
Pregnant women without dispensation of Selective Serotonin Reuptake Inhibitors (SSRIs) during the first 35 days of pregnancy. |
early pregnancy | 22884 / 1256956 | ||
| Information on use of prescription medication was collected from the National Prescription Register (the Register of Medicinal Product Statistics), that contains individual-level data on all prescribed drugs dispensed at all pharmacies in Denmark. | ||||||||
|
Andersen (Controls unexposed, sick) 2014 |
Denmark 1997 - 2010 population based cohort retrospective |
The Danish administrative health registries and linked through the CPR-number, a unique identification number given to all citizens. | Pregnant women dispensing of a prescription of fluoxetine, citalopram, paroxetine, sertraline or escitalopram (at least the first 35 days of pregnancy). |
unexposed, sick
Pregnant women with dispensation of Selective Serotonin Reuptake Inhibitors (SSRIs) 3–12 months before pregnancy but not after this period or during pregnancy. |
early pregnancy | 22884 / 14016 | ||
| Information on use of prescription medication was collected from the National Prescription Register (the Register of Medicinal Product Statistics), that contains individual-level data on all prescribed drugs dispensed at all pharmacies in Denmark. | ||||||||
|
Andrade 2009 |
USA 1996 - 2000 retrospective cohort |
Administrative databases of four health plans participating in the HMO Research Network Center for Education and Research on Therapeutics. | Infants whose mothers received a dispensing of selective serotonin reuptake inhibitors (SSRIs) during the third trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Random sample of infants whose mothers did not receive selective serotonin reuptake inhibitors (SSRIs) during the third trimester. |
3rd trimester | 933 / -9 | 1142 women (933 141 68) were exposed to antidepressant in 3rd trimester. Among these, only 38 with more than 1 class of antidepressant exposure. Exposure was considered as mono-class of antidepressants. | |
| Information on prescription drug dispensings was obtained from administrative databases at each health plan. | ||||||||
|
Avalos (Controls exposed to TCA) 2015 |
USA 2010 - 2012 retrospective cohort (claims database) |
Kaiser Permanente Northern California (KPNC). | Pregnant women with at least one pharmacy dispensing of selective serotonin reuptake inhibitors (SSRIs) between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women with at least one pharmacy dispensing of tricyclic antidepressant (TCA) between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
during pregnancy (anytime or not specified) | 1262 / 116 | Results of SSRI only and TCA only reported rather than 'SSRI only and SSRI plus other antidepressant' or 'TCA only and TCA plus other antidepressant'. | |
| Women exposed to antidepressant medications during pregnancy were identified through linkage to information on dates of drug dispensation and days of supply from the pharmacy database. | ||||||||
|
Avalos (Controls unexposed, disease free) 2015 |
USA 2010 - 2012 retrospective cohort (claims database) |
Kaiser Permanente Northern California (KPNC). | Pregnant women with at least one pharmacy dispensing of selective serotonin reuptake inhibitors (SSRIs) between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnant women without depression. |
during pregnancy (anytime or not specified) | 1262 / 16402 | Results of SSRI only reported rather than 'SSRI only and SSRI plus other antidepressant'. | |
| Women exposed to antidepressant medications during pregnancy were identified through linkage to information on dates of drug dispensation and days of supply from the pharmacy database. | ||||||||
|
Avalos (Controls unexposed, sick) 2015 |
USA 2010 - 2012 retrospective cohort (claims database) |
Kaiser Permanente Northern California (KPNC). | Pregnant women with at least one pharmacy dispensing of selective serotonin reuptake inhibitors (SSRIs) between the first day of the woman's last menstrual period (LMP) and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with untreated depression (diagnosed between 6 months prior to the woman's last menstrual period (LMP) and 20 completed weeks of gestation). |
during pregnancy (anytime or not specified) | 1262 / 1345 | Results of SSRI only reported rather than 'SSRI only and SSRI plus other antidepressant'. | |
| Women exposed to antidepressant medications during pregnancy were identified through linkage to information on dates of drug dispensation and days of supply from the pharmacy database. | ||||||||
|
Bakaysa 2016 |
USA 2009 - 2014 retrospective cohort |
Tufts Medical Center, Boston, USA. | Women who reported Selective Serotonin Reuptake Inhibitors (SSRI) use on admission. |
unexposed (general population or NOS)
Women who do not report Selective Serotonin Reuptake Inhibitors (SSRI) use on admission. |
late pregnancy | 112 / 224 | 'Fetal anomalies, stillbirths, and multiple gestations were excluded.'Women reported using the following: citalopram (n=23), escitalopram (n=4), paroxetine (n=2), fluoxetine (n=34), and sertraline (n=49). | |
| Not specified. | ||||||||
|
Ban (Controls exposed to TCA) 2014 |
United Kingdom 1990 - 2009 retrospective cohort (claims database) |
The Health Improvement Network (THIN), a nationally representative database of computerised primary care records. | Pregnant women with selective serotonin reuptake inhibitors (SSRIs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women with tricyclic antidepressants (TCAs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
1st trimester | 7683 / 2428 | Exclusion of 9096 children (2.5% of the study population) whose mothers had bipolar disorder, schizophrenia, other serious psychotic disorders, or prescriptions for antimanic and antipsychotic drugs before childbirth. Overlapping with Petersen 2016. | |
| The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions. | ||||||||
|
Ban (Controls exposed to TCA) 2012 |
The United Kingdom (UK). 1990 - 2009 population based cohort retrospective |
The Health Improvement Network (THIN), a nationally representative database of computerised primary care medical records collected at 446 general practices (primary health care units). | Pregnant women with prescriptions for any selective serotonin reuptake inhibitors (SSRIs) (alone - i.e. no other psychotropic medication of interest) during the first trimester. |
exposed to other treatment, sick
Pregnant women with prescriptions for any tricyclic antidepressants (TCAs) (alone - i.e. no other psychotropic medication of interest) during the first trimester. |
during pregnancy (anytime or not specified) | 14191 / 4349 | Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status. | |
| Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records. | ||||||||
|
Ban (Controls unexposed, disease free) 2014 |
United Kingdom 1990 - 2009 retrospective cohort (claims database) |
The Health Improvement Network (THIN), a nationally representative database of computerised primary care records. | Pregnant women with selective serotonin reuptake inhibitors (SSRIs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnant women without diagnosis of depression. |
1st trimester | 7683 / 325294 | Exclusion of 9096 children (2.5% of the study population) whose mothers had bipolar disorder, schizophrenia, other serious psychotic disorders, or prescriptions for antimanic, antipsychotic drugs before childbirth. Overlapping with Petersen 2015 and 2016. | |
| The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions. | ||||||||
|
Ban (Controls unexposed, disease free) 2012 |
The United Kingdom (UK). 1990 - 2009 population based cohort retrospective |
The Health Improvement Network (THIN), a nationally representative database of computerised primary care medical records collected at 446 general practices (primary health care units). | Pregnant women with prescriptions for any selective serotonin reuptake inhibitors (SSRIs) (alone - i.e. no other psychotropic medication of interest) during the first trimester. |
unexposed, disease free
Pregnant women without any indication of current or prior depression or anxiety. |
during pregnancy (anytime or not specified) | 14191 / -9 | Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status. Number of unexposed women not provided. | |
| Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records. | ||||||||
|
Ban (Controls unexposed, sick) 2014 |
United Kingdom 1990 - 2009 retrospective cohort (claims database) |
The Health Improvement Network (THIN), a nationally representative database of computerised primary care records. | Pregnant women with selective serotonin reuptake inhibitors (SSRIs) prescriptions from 4 weeks before to 12 weeks after the first day of the estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with depression diagnosed in the year before conception up to the end of the first trimester, but with no antidepressant drug prescriptions in the first trimester. |
1st trimester | 7683 / 13432 | Exclusion of 9096 children (2.5% of the study population) whose mothers had bipolar disorder, schizophrenia, other serious psychotic disorders, or prescriptions for antimanic, antipsychotic drugs before childbirth. Overlapping with Petersen 2015 and 2016. | |
| The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions. | ||||||||
|
Ban (Controls unexposed, sick) 2012 |
The United Kingdom (UK). 1990 - 2009 population based cohort retrospective |
The Health Improvement Network (THIN), a nationally representative database of computerised primary care medical records collected at 446 general practices (primary health care units). | Pregnant women with prescriptions for any selective serotonin reuptake inhibitors (SSRIs) (alone - i.e. no other psychotropic medication of interest) during the first trimester. |
unexposed, sick
Pregnant women with un-medicated depression or anxiety, i.e with current depression or anxiety but no prescriptions during the first trimester. |
during pregnancy (anytime or not specified) | 14191 / -9 | Mothers were grouped into eight mutually exclusive categories according to their diagnostic and treatment status. Number of unexposed women not provided. | |
| Prescriptions of all antidepressants, hypnotics, and anxiolytics extracted of The Health Improvement Network (THIN) that contains electronic medical records. | ||||||||
|
Batton 2013 |
USA 2000 - 2008 retrospective cohort |
Department of Pediatrics, Southern Illinois University School of Medicine, St. John’s Children’s Hospital, Springfield, Illinois. | Infants born preterm after in utero Selective serotonin reuptake inhibitors (SSRIs) exposure. |
unexposed, disease free
Infants without in utero Selective serotonin reuptake inhibitors (SSRIs) exposure and for which the mothers had no signs or symptoms of depression and no history of previous antidepressant treatment. |
during pregnancy (anytime or not specified) | 19 / 19 | ||
| SSRI prescription (or absence of such in controls) was documented in both the maternal antenatal records from the obstetrician’s office and the maternal hospital records. | ||||||||
|
Benevent 2023 |
France 2004 - 2019 retrospective cohort (claims database) |
EFEMERIS (Évaluation chez la Femme Enceinte des MÉdicaments et de leurs RISques) database, Haute-Garonne, France. | Pregnant women with at least one redeemed prescription of Selective serotonin reuptake inhibitors (SSRIs) monotherapy at least during the first trimester of pregnancy. |
unexposed (general population or NOS)
Pregnant women without redeemed prescription of antidepressants 3 months before and during pregnancy. |
1st trimester, at least 1st trimester, during pregnancy (anytime or not specified) | 1316 / 141865 | Data of the publication of Benevent 2023 completed with data of the unpublished report of Araujo 2022. Exclusion of receipt of both SSRIs and SNRIs 3 months before and during pregnancy. Results versus SNRIs not reported => inadequate control group. | |
| Prescriptions obtained from the French Health Insurance database (Haute Garonne), that included all drug prescriptions dispensed at pharmacies by patients receiving outpatient care, prior to and during pregnancy (names, ATC codes, dispensing dates, etc). | ||||||||
|
Bérard - Non Sertraline SSRI 2015 |
Canada 1998 - 2010 retrospective cohort (claims database) |
A register-based cohort study using data from the Quebec Pregnancy Cohort (QPC). | Depressed/anxious pregnancies with prescription fillings for Non-Sertraline selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, and fluvoxamine) dispensed during the first trimester of gestation. |
unexposed, sick
Pregnancies with a diagnosis or were treated with antidepressants in the year before their pregnancy but with no exposure to antidepressants (sertraline or others) during the first trimester of gestation. |
1st trimester | 1963 / 14868 | 2 group of SSRIs studied here => to avoid redundancy of control, only the non sertraline group was used. Overlapping: Ramos 2008 (1998-2002) included in this larger study. For major malfo: Bérard 2017 ('SSRI' as a whole) was used rather than Bérard 2015. | |
| Prescription fillings dispensed to women identified in the cohort from the Quebec public prescription drug insurance database. | ||||||||
|
Bérard a 2017 |
Canada 1998 - 2010 population based cohort propective |
A register-based cohort study using data from the Quebec Pregnancy Cohort (QPC). | Women that had filled at least one prescription for selective serotonin receptor inhibitors (SSRIs) during the time window of interest (between week 21 and date of birth). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Women that did not have filled prescription for antidepressant during the time window of of interest (between week 21 and date of birth). |
2nd and/or 3rd trimester | 1537 / 141097 | ||
| The Quebec Public Prescription Drug Insurance database (drug name, start date, dosage, duration). | ||||||||
|
Bérard b (Controls exposed to TCA) 2017 |
Canada 1998 - 2009 retrospective cohort (claims database) |
A register-based cohort study using data from the Quebec Pregnancy Cohort (QPC). | Depressed/anxious pregnancies with prescription fillings for Selective serotonin reuptake inhibitors (SSRI) dispensed during the first trimester of gestation. |
exposed to other treatment, sick
Depressed/anxious pregnancies with prescription fillings for Tricyclic antidepressants (TCA) dispensed during the first trimester of gestation. |
1st trimester | 2327 / 382 | Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study. For major malformations Bérard 2017 (that studied 'SSRI' as a whole) was used rather than Bérard 2015 (2 groups of exposure: Sertraline and 'other SSRIs'). | |
| Prescription fillings for sertraline dispensed to women identified in the cohort from the Quebec public prescription drug insurance database | ||||||||
|
Bérard b (Controls unexposed, sick) 2017 |
Canada 1998 - 2009 retrospective cohort (claims database) |
A register-based cohort study using data from the Quebec Pregnancy Cohort (QPC). | Depressed/anxious pregnancies with prescription fillings for Selective serotonin reuptake inhibitors (SSRI) dispensed during the first trimester of gestation. |
unexposed, sick
Pregnancies with a diagnosis or were treated with antidepressants in the year before their pregnancy but with no exposure to antidepressants during the first trimester of gestation. |
1st trimester | 2327 / 14847 | Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study. For major malformations Bérard 2017 (that studied 'SSRI' as a whole) was used rather than Bérard 2015 (2 groups of exposure: Sertraline and 'other SSRIs'). | |
| Prescription fillings for sertraline dispensed to women identified in the cohort from the Quebec public prescription drug insurance database | ||||||||
|
Bernard 2019 |
Canada 2005 - 2010 prospective cohort |
The CHU de Québec-Université Laval. | Pregnant women exposed to Selective serotonin reuptake inhibitors (SSRI) before the 16th week of pregnancy. |
unexposed, disease free
Pregnant women not exposed to the antidepressant/anxiolytic medication, depression or anxiety. |
at least 1st trimester | 117 / 6502 | ||
| Documentation on antidepressant medication was obtained following delivery from a standardized prenatal follow-up form filled at each prenatal visit by the nurse and the physician and included in the hospital records. | ||||||||
|
Bhatt-Mehta 2019 |
USA 2009 - 2017 retrospective cohort |
A high-risk obstetric clinic, for treatment of women with high-risk pregnancies due to drug dependence, part of a large obstetric and gynecology program at Michigan Medicine. | Infants with in-utero exposure to Selective Serotonin Reuptake Inhibitors (SSRIs) and opioids. |
unexposed, sick
Infants with in-utero exposure to opioids. |
during pregnancy (anytime or not specified) | 27 / 109 | ||
| These patients were identified from the electronic health record (EHR) of the high-risk clinic based on use of either opioid. The search for simultaneous presence of SSRIs occurred when these records were reviewed in detail for concomitant medication prescriptions along with opioids. | ||||||||
|
Bliddal (Controls unexposed, NOS) 2023 |
Denmark 1997 - 2015 population based cohort retrospective |
The Danish Medical Birth Register, the Danish National Birth Cohort (DNBC), the Danish Prescription Register, the Danish National Patient Register. | Singletons whose mothers redeemed any prescriptions on Selective serotonin reuptake inhibitor (SSRI) (ATC code N06AB) from 30 days prior to conception (which was defined as day of delivery minus gestational age) to the day of delivery. |
unexposed (general population or NOS)
Singletons whose mothers have no redeemed Selective serotonin reuptake inhibitor (SSRI) prescriptions from 2 years before conception until day of delivery. |
during pregnancy (anytime or not specified) | 22347 / 1094202 | Negative controls reporting confusion biais. Overlapping: Liu 2017 (1998 - 2012) included in Bliddal 2023 (1997 - 2015) => Only Bliddal 2023 used here because more exposed pregnancies. | |
| The Danish Prescription Register. | ||||||||
|
Bliddal (Controls unexposed, sick) 2023 |
Denmark 1997 - 2015 population based cohort retrospective |
The Danish Medical Birth Register, the Danish National Birth Cohort (DNBC), the Danish Prescription Register, the Danish National Patient Register. | Singletons whose mothers redeemed any prescriptions on Selective serotonin reuptake inhibitor (SSRI) (ATC code N06AB) from 30 days prior to conception (which was defined as day of delivery minus gestational age) to the day of delivery. |
unexposed, sick
Singletons whose mothers who used a Selective serotonin reuptake inhibitor (SSRI) between 2 years and 30 days prior to conception, but not during pregnancy. |
during pregnancy (anytime or not specified) | -9 / -9 | Negative controls reporting confusion biais. Overlapping: Liu 2017 (1998 - 2012) included in Bliddal 2023 (1997 - 2015) => Only Bliddal 2023 used here because more exposed pregnancies. | |
| The Danish Prescription Register. | ||||||||
|
Boukhris (Controls exposed to TCA) 2016 |
Canada 1998 - 2009 retrospective cohort (claims database) |
The Québec Pregnancy Children Cohort (QPC), a register-based study of an ongoing population-based cohort. | Infants who mothers having at least 1 prescription of selective serotonin reuptake inhibitors (SSRIs) filled at any time during pregnancy or before pregnancy that overlapped the first day of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women having at least 1 prescription of Tricyclic antidepressants filled at any time during pregnancy or before pregnancy that overlapped the first day of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
2nd and/or 3rd trimester | 1583 / 229 | 'Exposure to a single class was defined as the filling of prescriptions for only 1 AD class in the time window of interest.' | |
| The Public Prescription Drug Insurance database of Québec (drug name, start date, dose, and duration). Data on prescription filling for AD were validated against medical records and maternal reports. | ||||||||
|
Boukhris (Controls exposed to TCA) 2017 |
Canada 1998 - 2009 retrospective cohort (claims database) |
A register-based cohort study using data from the Quebec Pregnancy/Children Cohort (QPC). | Having at least one prescription filled of selective serotonin reuptake inhibitors (SSRIs) during the 2nd/3rd trimesters of pregnancy. (This is a subgroup of exposure among the whole exposed group considered). |
exposed to other treatment, sick
Having at least one prescription filled of tricyclic antidepressants (TCAs) during the 2nd/3rd trimesters of pregnancy. (This is a subgroup of exposure among the whole exposed group considered). |
2nd and/or 3rd trimester | 1561 / 227 | ‘Single class’ exposure was defined as the filling of prescrip- tions for only one AD class in the time window of interest. | |
| The Quebec’s Public Prescription Drug Insurance database (drug name, start date and duration), MedEcho database (diagnoses and procedures). | ||||||||
|
Boukhris (Controls unexposed, NOS) 2016 |
Canada 1998 - 2009 retrospective cohort (claims database) |
The Québec Pregnancy Children Cohort (QPC), a register-based study of an ongoing population-based cohort. | Infants who mothers having at least 1 prescription of selective serotonin reuptake inhibitors (SSRIs) filled at any time during pregnancy or before pregnancy that overlapped the first day of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Infants who were not exposed in utero to antidepressants. |
2nd and/or 3rd trimester | 1583 / 142924 | 'Exposure to a single class was defined as the filling of prescriptions for only 1 AD class in the time window of interest.' | |
| The Public Prescription Drug Insurance database of Québec (drug name, start date, dose, and duration). Data on prescription filling for AD were validated against medical records and maternal reports. | ||||||||
|
Boukhris (Controls unexposed, NOS) 2017 |
Canada 1998 - 2009 retrospective cohort (claims database) |
A register-based cohort study using data from the Quebec Pregnancy/Children Cohort (QPC). | Having at least one prescription filled of selective serotonin reuptake inhibitors (SSRIs) during the 2nd/3rd trimesters of pregnancy. (This is a subgroup of exposure among the whole exposed group considered). |
unexposed (general population or NOS)
Infants who were not exposed in utero to any antidepressants during the 2nd/3rd trimesters of pregnancy. |
2nd and/or 3rd trimester | 1561 / 141905 | ‘Single class’ exposure was defined as the filling of prescrip- tions for only one AD class in the time window of interest. | |
| The Quebec’s Public Prescription Drug Insurance database (drug name, start date and duration), MedEcho database (diagnoses and procedures). | ||||||||
|
Bracero 2016 |
USA 2003 - 2009 retrospective cohort |
A tertiary medical center in West Virginia, USA. | Pregnant women on both methadone and Selective serotonin reuptake inhibitors (SSRIs) at the time of delivery. |
unexposed, sick
Pregnant women on methadone at the time of delivery. |
days before delivery | 6 / 85 | The SSRIs used by the 6 patients were sertraline (2), fluoxetine (2), paroxetine (1), and escitalopram (1). | |
| The electronic medical system was queried for women on methadone maintenance. An electronic medical record review for data abstraction on both the mother’s and newborn’s medical records was performed. | ||||||||
|
Brennan 2023 |
USA Not specified. retrospective cohort |
The Environmental influences on Child Health Outcomes (ECHO) program, which combines longitudinal data across ongoing child cohort studies throughout the United States. | Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs). |
unexposed (general population or NOS)
No prenatal exposure to any antidepressants. |
during pregnancy (anytime or not specified) | 117 / 2966 | Exposure to SSRI about 72% of the 163 mothers with any antidepressant use (i.e 117). The most common SSRI medications were paroxetine and sertraline. | |
| Information on maternal prenatal antidepressants use was obtained from two sources in the ECHO database: the Maternal Medical Record Abstraction form (MMRA - medical records), and the Pregnancy Medical Conditions and Interventions (PMCI) questionnaire completed by the mothers (after delivery). | ||||||||
|
Brown 2017 |
Canada 2002 - 2010 retrospective cohort (claims database) |
Retrospective cohort study using health administrative data sets from Ontario, Canada. | Pregnant women with 2 or more consecutive prescriptions for a selective serotonin reuptake inhibitor (SSRI) medication filled between conception and delivery. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women with no serotonergic antidepressants prescribed during pregnancy or within 90 days prior to conception. |
during pregnancy (anytime or not specified) | 2167 / 33069 | ||
| Ontario Drug Benefit database. | ||||||||
|
Brown (Controls unexposed, disease free) 2016 |
Finland 1996 - 2010 population based cohort retrospective |
A population-based, prospective cohort study design. | Mothers diagnosed as having depression or another psychiatric disorder associated with one or more purchases of Selective serotonin reuptake inhibitors (SSRIs) during the period from 30 days before pregnancy until the end of pregnancy. |
unexposed, disease free
Mothers without a psychiatric diagnosis associated with SSRI use or a history of purchasing antidepressants or antipsychotics any time prior to or during pregnancy. |
during pregnancy (anytime or not specified) | 15596 / 31207 | ||
| The drug reimbursement register that contains data on all reimbursed prescription drug purchases throughout Finland and covers virtually all prescription drug purchases (99% in 2007). | ||||||||
|
Brown (Controls unexposed, sick) 2016 |
Finland 1996 - 2010 population based cohort retrospective |
A population-based, prospective cohort study design. | Mothers diagnosed as having depression or another psychiatric disorder associated with one or more purchases of Selective serotonin reuptake inhibitors (SSRIs) during the period from 30 days before pregnancy until the end of pregnancy. |
unexposed, sick
Mothers diagnosed as having depression or another psychiatric disorder (between 1 year before pregnancy and hospital discharge after delivery) associated with SSRI use with no history of SSRI purchase during pregnancy. |
during pregnancy (anytime or not specified) | 15596 / 9537 | ||
| The drug reimbursement register that contains data on all reimbursed prescription drug purchases throughout Finland and covers virtually all prescription drug purchases (99% in 2007). | ||||||||
|
Calderon-Margalit 2009 |
USA 1996 - nr prospective cohort |
The ongoing Omega Study, a prospective cohort study of pregnant mothers who attended prenatal care clinics affiliated with Swedish Medical Center (Seattle, Washington) and Tacoma General Hospital (Tacoma, Washington). | Pregnant women who used Selective serotonin receptor inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who did not use psychotropic medications during pregnancy. |
during pregnancy (anytime or not specified) | 132 / 2493 | Of the women who were taking psychotropic medications, 235 (78%) took only one medication, 51 (17%) used two medications, and 14 (5%) used three or more medications. | |
| Participants were interviewed during a prenatal visit prior to 20 weeks of gestation by trained research personnel using a structured questionnaire. Data on medications used during pregnancy were retrieved from both questionnaires and medical records. | ||||||||
|
Cantarutti (Controls unexposed, NOS) 2016 |
Italy 2005 - 2010 retrospective cohort (claims database) |
A population-based study carried out with data provided by the healthcare utilization database of Lombardy, Italy. | Dispensation of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered). |
unexposed (general population or NOS)
No dispensation of antidepressants during the pregnancy. |
during pregnancy (anytime or not specified) | -9 / 374830 | ||
| The National Health Service (NHS) including a database concerning outpatient drug prescriptions reimbursed by the NHS and delivered by pharmacies in Lombardy; | ||||||||
|
Cantarutti (Controls unexposed, sick) 2016 |
Italy 2005 - 2010 retrospective cohort (claims database) |
A population-based study carried out with data provided by the healthcare utilization database of Lombardy, Italy. | Dispensation of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered). |
unexposed, sick
Dispensation of antidepressants users just before conception, with at least an antidepressant dispensation in the 9 months before, but not during, pregnancy. |
during pregnancy (anytime or not specified) | -9 / 6548 | ||
| The National Health Service (NHS) including a database concerning outpatient drug prescriptions reimbursed by the NHS and delivered by pharmacies in Lombardy; | ||||||||
|
Casper 2003 |
USA Not specified prospective cohort |
Data from the Women’s Wellness Clinic. | Children of depressed mothers treated with selective serotonin reuptake inhibitors (SSRIs) at referral or started during pregnancy. |
unexposed, sick
Children whose mothers were diagnosed with major depressive disorder in pregnancy and elected not to take medication. |
during pregnancy (anytime or not specified) | 31 / 13 | Continuous variables other that mental and psychomotor development not reported here. | |
| Each woman completed a questionnaire that contained information about any drug exposure; the dose and timing of antidepressant drugs. | ||||||||
|
Chambers - Fluoxetine 1996 |
USA 1989 - 1995 prospective cohort |
The California Teratogen Information Service and Clinical Research Program. | Pregnant women exposed to fluoxetine during pregnancy. |
unexposed (general population or NOS)
Pregnant women who called the program with questions about drugs and procedures not considered teratogenic. |
1st trimester, late pregnancy | 228 / 254 | ||
| Each woman who enrolled in the study completed a questionnaire that included notably exposures during the current pregnancy. Each woman was provided with a diary in which she was asked to keep a record of any additional exposures that might occur before delivery. | ||||||||
|
Chan (Controls exposed to TCA) 2024 |
China 2003 - 2018 retrospective cohort (claims database) |
The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents. | Infants of women who were prescribed with Selective-serotonin-reuptake-inhibitors (SSRI) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester. |
exposed to other treatment, sick
Infants of women who were prescribed with Tricyclic-antidepressants (TCA) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester. |
1st trimester | 956 / 322 | ||
| Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records. | ||||||||
|
Chan (Controls unexposed, general pop) 2024 |
China 2003 - 2018 retrospective cohort (claims database) |
The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents. | Infants of women with prescription of Selective-serotonin-reuptake-inhibitors (SSRI) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester. |
unexposed (general population or NOS)
Infants of pregnant women who were not prescribed with any antidepressant within 90 days before the last menstrual period and during the first trimester. |
1st trimester | 956 / 462377 | ||
| Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records. | ||||||||
|
Chan (Controls unexposed, sick) 2024 |
China 2003 - 2018 retrospective cohort (claims database) |
The Clinical Data Analysis and Reporting System (CDARS), an electronic health-record database developed by the Hospital-Authority which is a statutory body delivering government-subsidized, universal health coverage to all Hong Kong residents. | Infants of women with depression/anxiety who were prescribed with Selective-serotonin-reuptake-inhibitors (SSRI) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester. |
unexposed, sick
Infants of pregnant women with depression/anxiety who were not prescribed with any antidepressant within 90 days before the last menstrual period and during the first trimester. |
1st trimester | 714 / 4413 | ||
| Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records. | ||||||||
|
Chen 2021 |
Taiwan 2000 - 2013 population based cohort retrospective |
The Taiwanese National Health Insurance Research Database (NHIRD). | Pregnant patients with perinatal depression with selective serotonin reuptake inhibitors (SSRIs) prescription. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant patients with perinatal depression with no antidepressant treatment 90 days before the date of their first pregnancy. |
during pregnancy (anytime or not specified) | 408 / 1789 | Meta-analysis of adjusted HR provided by authors according to defined daily doses. | |
| The National Health Insurance Research Database (NHIRD) which is a medical claims database and that includes drug prescription. | ||||||||
|
Cohen 2022 |
USA and United Kingdom 1999 - 2007 prospective cohort |
Two prior studies conducted at the Massachusetts General Hospital (MGH), Boston, USA and healthy developing control subjects from the United Kingdom. | Child exposed in utero to an selective serotonin reuptake inhibitor (SSRI) (at any point during pregnancy). |
unexposed, disease free
Healthy developing control subjects, unexposed to selective serotonin reuptake inhibitors (SSRIs) in utero. |
during pregnancy (anytime or not specified) | 54 / 18 | On average, children were exposed to an antidepressant during 90% of the pregnancy (SD=20%). | |
| Medication exposures were prospectively collected across pregnancy and the postpartum period (No other details). | ||||||||
|
Colvin 2011 |
Australia 2002 - 2005 retrospective cohort (claims database) |
A population-based linked datasets for the state of Western Australia. | Pregnant women who were dispensed an Selective Serotonin Reuptake Inhibitor (SSRI) during their pregnancy. |
unexposed (general population or NOS)
All other pregnant women and children of the women who were not dispensed a Selective Serotonin Reuptake Inhibitor (SSRI). |
1st trimester, 2nd and/or 3rd trimester, during pregnancy (anytime or not specified) | 3703 / 92995 | Overlapping of some outcomes (LBW, preterm, Apgar, Late intra-uterine death) with Colvin 2012 which include a little more pregnancies (and some adjustments and more relevant period of exposure), thus not reported here. | |
| The national Pharmaceutical Benefits Scheme (PBS), including dispensing in the community, private hospitals, and, since late 2004, public hospitals. | ||||||||
|
Colvin 2012 |
Australia 2002 - 2005 retrospective cohort (claims database) |
A population-based study of all pregnancy events in Western Australia (WA). | Children born to women who had been dispensed a selective serotonin reuptake inhibitor (SSRI) at any time during their pregnancy. |
unexposed (general population or NOS)
Children born to women who had not been dispensed a selective serotonin reuptake inhibitor (SSRI) at any time during their pregnancy. |
1st trimester, 2nd and/or 3rd trimester, during pregnancy (anytime or not specified) | 3764 / 94561 | ||
| The national Pharmaceutical Benefits Scheme (PBS), a claims database that includes 80% of all prescriptions dispensed in Australia. | ||||||||
|
Cornet - SSRIs 2024 |
USA 2011 - 2019 retrospective cohort (claims database) |
The 15 Kaiser Permanente Northern California (KPNC) hospitals. | Infants with any maternal Selective serotonin reuptake inhibitor (SSRI) dispensing by a KPNC pharmacy during late pregnancy, that is, after 20 weeks’ gestation. |
unexposed (general population or NOS)
Infants with no maternal Selective serotonin reuptake inhibitor (SSRI) dispensing by a KPNC pharmacy during late pregnancy, that is, after 20 weeks’ gestation. |
late pregnancy | 7573 / 272517 | SSRIs (ie, sertraline, fluoxetine, citalopram, escitalopram, paroxetine, dapoxetine, vortioxetine and fluvoxamine) => included non-SSRI (vortioxetine), but very low number of exposures (< 90%) => considered as SSRIs. | |
| Prescription files of Kaiser Permanente Northern California pharmacies. For each prescription, dispensation date, daily dosage and number of pills dispensed were collected. | ||||||||
|
Corti 2019 |
Italy 2011- 2016 prospective cohort |
The Unit of Obstetrics-Gynecology, Sacco Hospital, Milan | Caucasian women with a diagnosis of depression and/or anxiety in treatment with selective serotonin reuptake inhibitors (SSRIs) before and during conception. |
unexposed, disease free
Caucasian women, without a psychiatric diagnosis and not exposed to psychotropic medications before and during pregnancy (the first two deliveries immediately after each SSRI case). |
throughout pregnancy | 42 / 85 | 'Women who stopped taking medication before or during labor were excluded from the study.'. ' Exclusion criteria for both groups were other psychotropic drugs' | |
| Pregnancies were prospectively enrolled. All exposed pregnancies were followed in a prospective way by our multidisciplinary team, that checked drug compliance at each visit during the whole pregnancy up to delivery. Unexposed: the first two deliveries immediately after each SSRI exposed. | ||||||||
|
Costei - Paroxetine (Controls unexposed, NOS) 2002 |
Canada 1996 - 1999 prospective cohort |
The Motherisk program | Pregnant women exposed to paroxetine throughout the third trimester. |
unexposed (general population or NOS)
Pregnant women who used nonteratogenic drugs. |
3rd trimester | 55 / 27 | Authors also considered a mixed control group: women who used paroxetine only during the 1st and/or 2nd trimesters and women who used nonteratogenic drugs. => Not considered here because the 2 separate control group seem more relevant. | |
| At the time of counseling (during pregnancy), detailed exposure data and information on all other drugs used concomitantly were collected by maternal interview. | ||||||||
|
Costei - Paroxetine (Controls unexposed, sick) 2002 |
Canada 1996 - 1999 prospective cohort |
The Motherisk program | Pregnant women exposed to paroxetine throughout the third trimester. |
unexposed, sick
Pregnant women who used paroxetine only during the first and/or second trimesters. |
3rd trimester | 55 / 27 | Authors also considered a mixed control group: women who used paroxetine only during the 1st and/or 2nd trimesters and women who used nonteratogenic drugs. => Not considered here because the 2 separate control group seem more relevant. | |
| At the time of counseling (during pregnancy), detailed exposure data and information on all other drugs used concomitantly were collected by maternal interview. | ||||||||
|
Davidson 2009 |
Israel July - Dec 2005 retrospective cohort |
Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqwa 49 100, Israel. | Pregnant women took Selective serotonin reuptake inhibitors (SSRIs) during the entire pregnancy |
unexposed, disease free
Healthy pregnant women who did not take Selective serotonin reuptake inhibitors (SSRIs) or other medications. |
throughout pregnancy | 21 / 20 | Women with diabetes, chronic hypertension, and cardiovascular diseases were excluded from participation in the study. Eight mothers (38%) received paroxetine, seven (33%) fluoxetine, and six (29%) citalopram. | |
| A detailed questionnaire covering medications during pregnancy was completed for each participant after delivery. | ||||||||
|
Davis 2007 |
USA 1996 - 2000 retrospective cohort (claims database) |
A population-based cohort based on five health maintenance organizations (HMOs) participating in the HMO Research Network’s Center for Education and Research on Therapeutics (CERTs). | Fullterm infants exposed in utero to selective serotonin reuptake inhibitor (SSRI) (trimester of exposure according to outcomes). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Fullterm infants unexposed to selective serotonin reuptake inhibitor (SSRIs). |
1st trimester, 3rd trimester, during pregnancy (anytime or not specified) | 1768 / 79759 | Polyhydramnios, Oligohydramnios, Poly- and/or oligo-hydramnios not reported because not sure that the 3rd trimester exposure occurred before outcome. | |
| Information on prescribed antidepressant medications was derived from the pharmacy database files available at each health system. | ||||||||
|
De Ocampo 2016 |
USA and Canada 2004 - 2014 prospective cohort |
The MotherToBaby (MTB) USA and Canada and MTB California cohort studies. | Pregnant women who use selective serotonin reuptake inhibitors (SSRIs) alone during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who did not use antidepressants at any time during pregnancy. |
1st and 2nd trimester, throughout pregnancy | 157 / 3119 | Two exposed groups: discontinuers (women who discontinued use <20 weeks of gestation) or continuers (women who continued use ≥20 weeks of gestation). Continuers reported here because it maximize the potential effect and there are more pregnancies. | |
| After enrollment, the women completed a comprehensive intake interview and use of prescription and over-the-counter medications were collected. Information on exposures collected at intake was updated at each successive interview (every 3 months until the end of the pregnancy). | ||||||||
|
de Vries 2013 |
The Netherlands 2007 - 2010 prospective cohort |
The Dutch SMOK trial (SSRIs in pregnant mothers, outcome of the kids) | Selective serotonin reuptake inhibitors (SSRI) for depression and/or anxiety disorder during pregnancy and already taking medication before conception. |
unexposed (general population or NOS)
Pregnant women that did not use a Selective serotonin reuptake inhibitors (SSRI) (or psychotropic medication) during pregnancy (healthy or with depression and/or anxiety unmedicated). |
during pregnancy (anytime or not specified) | 63 / 44 | 'Venlafaxine was considered to work as an SSRI if being dosed low; women using venlafaxine ,200 mg were included in the SSRI group'. Control group included: healthy women (n=35) and depressed unmedicated (n=9). | |
| Women, in any stage of pregnancy and in both groups, were either self-referred, after reading about our study in the local newspapers, or referred by their gynaecologist, psychiatrist, midwife, or general practitioner. | ||||||||
|
Diav-Citrin - Fluoxetine or Paroxetine 2008 |
Israel, Italy and Germany 1994 - 2005 prospective cohort |
The Israeli Teratology Information Service, Servizio di Informazione Teratologica, or Pharmakovigilanz-und Beratungszentrum für Embryonaltoxikologie. | Pregnant women who contacted one Teratology Information Service regarding exposures to Fluoxetine or Paroxetine (sum of paroxetine and fluoxetine exposures). |
unexposed (general population or NOS)
Pregnant women who contacted one Teratology Information Service regarding exposures known not to be teratogenic in similar time frames. |
1st trimester, during pregnancy (anytime or not specified) | 809 / 1467 | Monotherapy: Author's answer: 'As far as we know, all women were exposed to only one of these two drugs.' => Thus sum of paroxetine and fluoxetine exposures, except for the 2 adjusted results (use of Paroxetine data because more exposed pregnancies). | |
| Details of exposure were collected at the initial contact with the TIS and before pregnancy outcome was known using a structured questionnaire. SSRIs and other exposures were also ascertained after delivery. | ||||||||
|
Dubnov-Raz 2008 |
Israel 2000 - 2005 prospective cohort |
The Rabin Medical Center Department of Neonatology, Israel. | Newborns exposed to selective serotonin-reuptake inhibitor antidepressants in the immediate antepartum period. |
unexposed, disease free
Newborns born to healthy mothers who took no medications before delivery. |
days before delivery | 52 / 52 | Paroxetine (n = 25), citalopram (n = 13), fluoxetine (n = 12), fluvoxamine (n = 1), and venlafaxine (n = 1) => Mainly SSRI (24/25), thus considered as SSRI. | |
| Not specified. | ||||||||
|
Edelson 2020 |
USA Not specified retrospective cohort |
Not specified | Pregnant women who were on buprenorphine and selective serotonin reuptake inhibitors (SSRI). |
unexposed, sick
Pregnant women who were on buprenorphine without selective serotonin reuptake inhibitors (SSRI). |
during pregnancy (anytime or not specified) | 12 / 37 | Two possible analyses: buprenorphine or methadone. The buprenorphine analysis was chosen because there is more exposed pregnancies to SSRI and induced less NAS. | |
| Medication regimens were ascertained by chart review. | ||||||||
|
Einarson 2001 |
Canada, USA, Italy, and Brazil. Not specified prospective cohort |
The Motherisk Program and the other participating pregnancy counseling centers. | Pregnant women suffering from depression who were taking selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, sertraline, fluvoxamine, and paroxetine). |
unexposed (general population or NOS)
Pregnant women who were given nonteratogenic drugs (loperamide, echinacea, sumatriptan, and dextromethorphan). |
1st trimester, during pregnancy (anytime or not specified) | 150 / 150 | Overlapping: The outcome 'Major malformation' is not reported here because a larger study published by Einarson et al. 2009 (n=506 SSRI exposures) could include the same cases. | |
| On successful contact, information on each woman’s exposure history and pregnancy outcome were obtained, along with other measures of interest, with the aid of a structured questionnaire. | ||||||||
|
Einarson 2009 |
Canada Not specified. prospective cohort |
The Motherisk Program, a teratogenic information service. | Pregnant women who were exposed to selective serotonin reuptake inhibitors (SSRIs) in the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who were not exposed to antidepressants and who had called Motherisk for information regarding nonteratogenic drugs. |
1st trimester | 527 / 928 | Addition of raw data provided for citalopram (184), escitalopram (21), fluvoxamine (52), paroxetine (148), fluoxetine (61) and sertraline (61). | |
| During the initial telephone contact, details of exposure and concurrent exposures are recorded on a standardized questionnaire. | ||||||||
|
Einarson - Paroxetine 2008 |
Italy, Switzerland, Australia, Canada, Germany, Israel, USA and Finland Not specified. prospective cohort |
Data of eight teratology information services (TIS). | First-trimester paroxetine exposure. |
unexposed (general population or NOS)
Other women who called teratology information services inquiring about exposures to drugs that are considered safe in pregnancy. |
1st trimester | 1174 / -9 | Only the 1,174 unpublished cases of first-trimester paroxetine exposure from eight teratology information services were reported here. The other 2,061 cases from five previously published database studies are not reported here. | |
| During the initial telephone contact, details of exposure and concurrent exposures are recorded on a standardized questionnaire form. Details about the exposure include duration, timing in pregnancy, dose, frequency, and medical indication for use of the drug. | ||||||||
|
El Marroun (Control unexposed, disease free) 2014 |
The Netherlands 2002 - 2006 prospective cohort |
An ongoing population-based cohort, the Generation R Study. | Pregnant women who used Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, disease free
Pregnant women whitout exposure to Selective serotonin reuptake inhibitors (SSRIs) and a low score of maternal depressive symptoms. |
1st trimester, during pregnancy (anytime or not specified) | 69 / 5531 | ||
| Exposure to Selective serotonin reuptake inhibitors (SSRIs) was assessed during pregnancy, using two sources of information: (a) self-report assessed with questionnaires and (b) prescription records from pharmacies. | ||||||||
|
El Marroun (Control unexposed, sick) 2014 |
The Netherlands 2002 - 2006 prospective cohort |
An ongoing population-based cohort, the Generation R Study. | Pregnant women who used Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, sick
Pregnant women with clinically relevant depressive symptoms and no maternal Selective serotonin reuptake inhibitors (SSRIs) use. |
during pregnancy (anytime or not specified) | 69 / 376 | ||
| Exposure to Selective serotonin reuptake inhibitors (SSRIs) was assessed during pregnancy, using two sources of information: (a) self-report assessed with questionnaires and (b) prescription records from pharmacies. | ||||||||
|
El Marroun (Controls unexposed, disease free) 2012 |
The Netherlands 2002 - 2006 prospective cohort |
The Generation R Study, a prospective population-based study from early fetal life onward. | Women using Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, disease free
Women not using Selective serotonin reuptake inhibitors (SSRIs) with low depressive symptoms |
during pregnancy (anytime or not specified) | 99 / 7027 | ||
| Maternal SSRI use during pregnancy assessed by 2 sources of information: (1) self-reports assessed with questionnaires and (2) prescription records from pharmacies. In each trimester, participants reported whether they had used any medication. | ||||||||
|
El Marroun (Controls unexposed, sick) 2012 |
The Netherlands 2002 - 2006 prospective cohort |
The Generation R Study, a prospective population-based study from early fetal life onward. | Women using Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, sick
Women with clinically relevant depressive symptoms and not using Selective serotonin reuptake inhibitors (SSRIs). |
during pregnancy (anytime or not specified) | 99 / 570 | ||
| Maternal SSRI use during pregnancy assessed by 2 sources of information: (1) self-reports assessed with questionnaires and (2) prescription records from pharmacies. In each trimester, participants reported whether they had used any medication. | ||||||||
|
Engelstad (Controls unexposed, disease free) 2014 |
USA 2009 - 2011 retrospective cohort |
Linked maternal-neonatal records of women who delivered at the University of Iowa Hospitals and Clinics (UIHC). | Pregnant women who had an ICD-9 code for depression and who were prescribed selective serotonin reuptake inhibitors (SSRIs). |
unexposed, disease free
Pregnant women who did not have any of the ICD-9 codes for depression. |
during pregnancy (anytime or not specified) | 126 / 222 | In exposed group: 'Two women received an SSRI plus bupropion, and one woman received sertraline plus bupropion and nortriptyline'=> considered as monotherapy of SSRI. | |
| The use of antidepressants during pregnancy was identified based on medication record and medical chart review. | ||||||||
|
Engelstad (Controls unexposed, sick) 2014 |
USA 2009 - 2011 retrospective cohort |
Linked maternal-neonatal records of women who delivered at the University of Iowa Hospitals and Clinics (UIHC). | Pregnant women who had an ICD-9 code for depression and who were prescribed selective serotonin reuptake inhibitors (SSRIs). |
unexposed, sick
Pregnant women with depression that did not receive a selective serotonin reuptake inhibitors (SSRI) (with 82% of no antidepressant and 18% of other antidepressants). |
during pregnancy (anytime or not specified) | 126 / 128 | In exposed group: 'Two women received an SSRI plus bupropion, and one woman received sertraline plus bupropion and nortriptyline'=> considered as monotherapy of SSRI. | |
| The use of antidepressants during pregnancy was identified based on medication record and medical chart review. | ||||||||
|
Figueroa 2010 |
USA 1997 - 2006 retrospective cohort (claims database) |
The MarketScan data used in this study, collected by Thompson Reuters (previously Medstat), obtained from large self-insured employers from all states, except Alaska and Hawaii. | Children born to mothers with a prescription filled of Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, sick
Children born to depressed mothers who were not exposed to antidepressants during pregnancy |
1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified) | 916 / 3532 | ||
| The MarketScan data contain information including prescription claims and the date of the service. | ||||||||
|
Frayne 2021 |
Australia Not specified retrospective cohort |
The King Edward Memorial Hospital in Perth and Mercy Hospital for Women in Melbourne, Australia. | Pregnant women that use Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women who were not taking, and had not taken, antidepressant, mood stabilizing and antiepileptic agents during the pregnancy. |
1st trimester, throughout pregnancy | 108 / 238 | 'Data were extracted from a larger dataset: Galbally et al. 2020' | |
| Psychotropic medication usage was extracted from the medical records and included information for first trimester and third trimester exposure as well as dosage. | ||||||||
|
Furu (Controls unexposed, NOS) 2015 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2010 population based cohort retrospective |
Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers. | Infants born to women who filled a prescription for a Selective serotonin reuptake inhibitors (SSRI) from 30 days before the first day of the last menstrual period until the end of the first trimester (defined as 97 days after the last menstrual period). |
unexposed (general population or NOS)
Infants not exposed to any antidepressant (ATC code N06A) in utero. |
1st trimester | 36772 / 2266875 | The group Any SSRI included SSRI and Venlafaxine (less than 10% of exposed group (2763/36772=7.5%)), thus the 'Any SSRI' is considered as SSRI. Overlapping: Furu 2015 included Norby 2006, Malm 2005, Pedersen 2009, Wogelius 2006, Lennestal 2007. | |
| The Nordic prescription registers include data on dispensed drugs, substance, brand name, and formulation, together with date of dispensing. | ||||||||
|
Furu (Controls unexposed, sibling) 2015 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2010 population based cohort retrospective |
Sibling cohort - Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers. | Infants born to women who filled a prescription for a Selective serotonin reuptake inhibitors (SSRI) from 30 days before the first day of the last menstrual period until the end of the first trimester (defined as 97 days after the last menstrual period). |
sibling
Siblings born to the same mother but not exposed to any antidepressant (ATC code N06A) in utero. |
1st trimester | 980 / 1308 | The exposed group Any SSRI included SSRI and Venlafaxine (not a SSRI). Venlafaxine represents less than 10% of exposed group (2763/36772=7.5%), thus the 'Any SSRI' group is considered to represent SSRI even if it includes Venlafaxine. | |
| The Nordic prescription registers include data on dispensed drugs, substance, brand name, and formulation, together with date of dispensing. | ||||||||
|
Galbally (Controls unexposed, disease free) 2020 |
Australia 2012 - 2017 prospective cohort |
Mercy Pregnancy and Emotional Wellbeing Study, a prospective pregnancy cohort study in Melbourne, Victoria, Australia | Pregnant women taking Selective serotonin reuptake inhibitors (SSRIs) in pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnant women who met no diagnostic criteria and were not taking antidepressants. |
during pregnancy (anytime or not specified) | 60 / 348 | Overlapping: results of preeclampsia specifically studied in Frayne 2021(with a little more pregnancies), thus results reported in Galbally 2020 not included in Metapreg. | |
| Antidepressant type, usage, dosage and timing during pregnancy was self-reported by women at each time point, as well as obtained from hospital records at delivery and drug levels in maternal and cord blood. | ||||||||
|
Galbally (Controls unexposed, sick) 2020 |
Australia 2012 - 2017 prospective cohort |
Mercy Pregnancy and Emotional Wellbeing Study, a prospective pregnancy cohort study in Melbourne, Victoria, Australia | Pregnant women taking Selective serotonin reuptake inhibitors (SSRIs) in pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Non-medicated pregnant women who met diagnostic criteria on a structured interview for current or past (within 2 years of pregnancy) depression or dysthymia at recruitment. |
during pregnancy (anytime or not specified) | 60 / 47 | Overlapping: results of preeclampsia specifically studied in Frayne 2021(with a little more pregnancies), thus results reported in Galbally 2020 not included in Metapreg. | |
| Antidepressant type, usage, dosage and timing during pregnancy was self-reported by women at each time point, as well as obtained from hospital records at delivery and drug levels in maternal and cord blood. | ||||||||
|
Giardinelli (Controls unexposed, disease free) 2018 |
Italy 2014- 2015 prospective cohort |
The outpatient clinic for perinatal mental health at the University of Florence, Italy. | Pregnant with diagnosis of major depression treated with selective serotonin reuptake inhibitors (SSRIs) and psychological support. |
unexposed, disease free
Consecutive healthy pregnant women. |
during pregnancy (anytime or not specified) | 24 / 26 | ||
| Pregnant women were exposed to pharmacotherapy according to the severity of depression diagnosed in the clinic for perinatal mental health at the University of Florence. | ||||||||
|
Giardinelli (Controls unexposed, sick) 2018 |
Italy 2014- 2015 prospective cohort |
The outpatient clinic for perinatal mental health at the University of Florence, Italy. | Pregnant with diagnosis of major depression treated with selective serotonin reuptake inhibitors (SSRIs) and psychological support. |
unexposed, sick
Pregnant with diagnosis of major depression treated with psychological support only. |
during pregnancy (anytime or not specified) | 24 / 23 | ||
| Pregnant women were exposed to pharmacotherapy according to the severity of depression diagnosed in the clinic for perinatal mental health at the University of Florence. | ||||||||
|
Gover 2023 |
Israel 2015 - 2022 retrospective cohort |
The neonatal intensive care unit (NICU) at the Carmel Medical Center, Haifa, Israel. | Preterm infants with a positive history of maternal Selective serotonin reuptake inhibitors (SSRIs) use throughout the pregnancy. |
unexposed (general population or NOS)
Preterm infants with a confirmed negative history of maternal Selective serotonin reuptake inhibitors (SSRIs) use throughout the pregnancy. |
throughout pregnancy | 21 / 21 | Because all included infants were admitted to neonatal intensive care unit (NICU), only the parameter 'Delivery room advanced resuscitation' was reported as a proxy of severity. | |
| Data were retrospectively collected from an electronic health record database (Metavision®, iMDsoft). Records were reviewed using MetaVision’s Query Wizard tool, identifying infants admitted to neonatal intensive care unit with completed data on maternal drug use during pregnancy. | ||||||||
|
Grzeskowiak (Controls unexposed, disease free) 2013 |
Denmark 1996 - 2002 population based cohort retrospective |
The Danish National Birth Cohort (DNBC), an ongoing nationwide, follow-up study of pregnant women and their children. | Pregnant women that reported taking a selective serotonin reuptake inhibitor (SSRI) at any stage during pregnancy. |
unexposed, disease free
Pregnant women who did not have a psychiatric illness and did not receive a dispensing for an SSRI. |
during pregnancy (anytime or not specified) | 127 / 35568 | Exclusion of women who took psychotropic medications other than SSRIs during pregnancy (i.e., anxiolytics, antipsychotics, antiepileptics or other antidepressants). | |
| At the time of providing consent, women were asked to report on medication use during early pregnancy in a self-administered questionnaire (at approx. 6-10 weeks of gestation). Information on drug use was also obtained from the 2 other women telephone interviews during pregnancy. | ||||||||
|
Grzeskowiak (Controls unexposed, sick) 2013 |
Denmark 1996 - 2002 population based cohort retrospective |
The Danish National Birth Cohort (DNBC), an ongoing nationwide, follow-up study of pregnant women and their children. | Pregnant women that reported taking a selective serotonin reuptake inhibitor (SSRI) at any stage during pregnancy. |
unexposed, sick
Pregnant women with a psychiatric illness during pregnancy but who did not receive a dispensing for an SSRI or any other antidepressant during pregnancy. |
during pregnancy (anytime or not specified) | 127 / 490 | Exclusion of women who took psychotropic medications other than SSRIs during pregnancy (i.e., anxiolytics, antipsychotics, antiepileptics or other antidepressants). | |
| At the time of providing consent, women were asked to report on medication use during early pregnancy in a self-administered questionnaire (at approx. 6-10 weeks of gestation). Information on drug use was also obtained from the 2 other women telephone interviews during pregnancy. | ||||||||
|
Grzeskowiak a (Controls unexposed, disease free) 2012 |
Australia 2000 - 2008 retrospective cohort |
The Women’s and Children’s Health Network (WCHN) in South Australia, including the Perinatal Statistics Collection and the Hospital Pharmacy Dispensing Records. | Pregnant women that received a dispensing for a selective serotonin reuptake inhibitors (SSRI) during pregnancy. |
unexposed, disease free
Pregnant women who did not have a psychiatric illness and did not receive a dispensing for an SSRI. |
during pregnancy (anytime or not specified) | 221 / 32004 | Exclusion of women who were taking antidepressants other than SSRIs during pregnancy (n = 93) and those who were taking antipsychotics (n = 81). | |
| Data on exposure to SSRIs during pregnancy were obtained from the Women’s and Children’s Hospital (WCH) Pharmacy Dispensing Records, which is a record of all medications dispensed. | ||||||||
|
Grzeskowiak a (Controls unexposed, sick) 2012 |
Australia 2000 - 2008 retrospective cohort |
The Women’s and Children’s Health Network in South Australia, including the Perinatal Statistics Collection and the Hospital Pharmacy Dispensing Records. | Pregnant women that received a dispensing for a selective serotonin reuptake inhibitors (SSRI) during pregnancy. |
unexposed, sick
Pregnant women with a psychiatric illness during pregnancy but who did not receive a dispensing for an SSRI or any other antidepressant during pregnancy. |
during pregnancy (anytime or not specified) | 221 / 1566 | Exclusion of women who were taking antidepressants other than SSRIs during pregnancy (n = 93) and those who were taking antipsychotics (n = 81). | |
| Data on exposure to SSRIs during pregnancy were obtained from the WCH Pharmacy Dispensing Records, which is a record of all medications dispensed. | ||||||||
|
Grzeskowiak b (Controls unexposed, disease free) 2012 |
Australia 2000 - 2005 retrospective cohort |
The Women’s and Children’s Health Network (WCHN) in South Australia, including the Perinatal Statistics Collection and the Hospital Pharmacy Dispensing Records. | Pregnant women that received a dispensing for a selective serotonin reuptake inhibitors (SSRI) during pregnancy. |
unexposed, disease free
Pregnant women that did not have a reported psychiatric illness and did not receive a dispensing for any antidepressant. |
during pregnancy (anytime or not specified) | 71 / 6285 | Exclusion of women who were dispensed an antidepressant other than SSRIs during pregnancy, antipsychotics, and anti-epileptics, as well as women with asthma, hypertension, diabetes, gestational diabetes and thyroid disorders. | |
| Data on exposure to SSRIs during pregnancy were obtained from the WCH Pharmacy Dispensing Records, which is a record of all medications dispensed. | ||||||||
|
Grzeskowiak b (Controls unexposed, sick) 2012 |
Australia 2000 - 2005 retrospective cohort |
The Women’s and Children’s Health Network (WCHN) in South Australia, including the Perinatal Statistics Collection and the Hospital Pharmacy Dispensing Records. | Pregnant women that received a dispensing for a selective serotonin reuptake inhibitors (SSRI) during pregnancy. |
unexposed, sick
Pregnant women with a psychiatric illness during pregnancy but who did not receive a dispensing for an SSRI or any other antidepressant during pregnancy. |
during pregnancy (anytime or not specified) | 71 / 204 | Exclusion of women who were dispensed an antidepressant other than SSRIs during pregnancy, antipsychotics, and anti-epileptics, as well as women with asthma, hypertension, diabetes, gestational diabetes and thyroid disorders. | |
| Data on exposure to SSRIs during pregnancy were obtained from the WCH Pharmacy Dispensing Records, which is a record of all medications dispensed. | ||||||||
|
Gungor (Controls exposed to Mirtazapine) 2019 |
Turkey 2015 - 2018 prospective cohort |
Not specified | Pregnant women medicated with selective serotonine reuptake inhibitor (SSRI) as a single treatment. |
exposed to other treatment, sick
Pregnant women medicated with mirtazapine as a single treatment. |
during pregnancy (anytime or not specified) | 40 / 16 | The exclusion criteria were the use of medications (including antihistaminic agents, benzodiazepines, herbal medicine, antipsychotics) other than SSRI or mirtazapine for psychiatric disorder... | |
| Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit. | ||||||||
|
Gungor (Controls unexposed, disease free) 2019 |
Turkey 2015 - 2018 prospective cohort |
Not specified | Pregnant women medicated with selective serotonin reuptake inhibitors (SSRIs) as a single treatment. |
unexposed, disease free
Healthy women with no current nor previous psychiatric disorder history. |
during pregnancy (anytime or not specified) | 40 / 23 | The exclusion criteria were the use of medications (including antihistaminic agents, benzodiazepines, herbal medicine, antipsychotics) other than SSRI or mirtazapine for psychiatric disorder... | |
| Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit. | ||||||||
|
Gungor (Controls unexposed, sick) 2019 |
Turkey 2015 - 2018 prospective cohort |
Not specified | Pregnant women medicated with selective serotonin reuptake inhibitors (SSRIs) as a single treatment. |
unexposed, sick
Pregnant women with unmedicated psychiatric disorder. |
during pregnancy (anytime or not specified) | 40 / 23 | The exclusion criteria were the use of medications (including antihistaminic agents, benzodiazepines, herbal medicine, antipsychotics) other than SSRI or mirtazapine for psychiatric disorder... | |
| Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit. | ||||||||
|
Hagberg (Controls exposed to TCA) 2018 |
United Kingdom 1989 - 2011 retrospective cohort (claims database) |
The UK Clinical Practice Research Datalink (CPRD), a large, population-based electronic medical database. | Pregnant women with depression treated with Selective serotonin reuptake inhibitors (SSRIs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered). |
exposed to other treatment, sick
Pregnant women with depression treated with tricyclic antidepressants (TCAs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered). |
during pregnancy (anytime or not specified) | 17362 / 4856 | For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept. | |
| The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs. | ||||||||
|
Hagberg (Controls unexposed, disease free) 2018 |
United Kingdom 1989 - 2011 retrospective cohort (claims database) |
The UK Clinical Practice Research Datalink (CPRD), a large, population-based electronic medical database. | Pregnant women with depression treated with Selective serotonin reuptake inhibitors (SSRIs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered). |
unexposed, disease free
Pregnant women who had neither depression nor prescriptions for antidepressants prior to the baby’s delivery date. |
during pregnancy (anytime or not specified) | 17362 / 154107 | For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept. | |
| The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs. | ||||||||
|
Hagberg (Controls unexposed, sick) 2018 |
United Kingdom 1989 - 2011 retrospective cohort (claims database) |
The UK Clinical Practice Research Datalink (CPRD), a large, population-based electronic medical database. | Pregnant women with depression treated with Selective serotonin reuptake inhibitors (SSRIs) only (diagnosis and ≥1 antidepressant prescription during the exposure period). (This is a subgroup of exposure among the whole exposed group considered). |
unexposed, sick
Pregnant women with untreated depression (recent history of treated depression but no antidepressants during the exposure period). |
during pregnancy (anytime or not specified) | 17362 / 12994 | For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept. | |
| The UK Clinical Practice Research Datalink (CPRD) where participating general practitioners (GPs) contributed de-identified data including details of prescription drugs. | ||||||||
|
Handal a 2016 |
Norway 1999 - 2008 population based cohort propective |
The Norwegian Mother and Child Cohort study (MoBa), a population-based prospective pregnancy cohort study. | Pregnant women that report any use of selective serotonin reuptake inhibitors (SSRIs) from pregnancy week 0 until birth. |
unexposed (general population or NOS)
Pregnant women that did not report any use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
during pregnancy (anytime or not specified) | 381 / 51023 | Addition of the 2 subgroups: 'One period' and 'At least two periods' of exposure during pregnancy. | |
| The mothers received three questionnaires with questions regarding drug use before and during pregnancy: during pregnancy (week 17/18 and week 30) and 6 months after birth. | ||||||||
|
Hanley 2016 |
Canada 2002 - 2011 retrospective cohort (claims database) |
A population-based cohort study in British Columbia, Canada. | A supply of selective serotonin reuptake inhibitors (SSRIs) during pregnancy (late- or mid-pregnancy exposure). (This is a subgroup of exposure among the whole exposed group considered). |
unexposed (general population or NOS)
No supply of any antidepressants in the 5 months before delivery (during mid- to late pregnancy) |
2nd trimester, late pregnancy | 6637 / 310813 | 'We excluded all women using “other antidepressants” (such as amitriptyline, bupropion, and trazodone) from our final analyses. Women using combination SSRI and serotonin–norepinephrine reuptake inhibitor therapy were also excluded.' | |
| The British Columbia PharmaNet (a prescription dispensation database into which all prescriptions dispensed must be entered by law). | ||||||||
|
Hannerfors (Controls unexposed, NOS) 2015 |
Sweden ? - 2013 retrospective cohort |
Two studies at the Department of Women’s and Children’s Health, Uppsala University hospital, Sweden. | Pregnant women treated with serotonin reuptake inhibitors (SSRI) at the time of the blood sampling (16—20 weeks of gestation). |
unexposed (general population or NOS)
Untreated pregnant women. |
1st and 2nd trimester, during pregnancy (anytime or not specified) | 207 / 609 | ||
| The study subjects complete web-based self-administrated structured questionnaires containing questions on ongoing medication. The medical records of the women who were on SSRI were reviewed to verify the self-reported SSRI use and to ensure that SSRI had been used during the entire pregnancy. | ||||||||
|
Hannerfors (Controls unexposed, sick) 2015 |
Sweden ? - 2013 retrospective cohort |
Two studies at the Department of Women’s and Children’s Health, Uppsala University hospital, Sweden. | Pregnant women treated with serotonin reuptake inhibitors (SSRI) at the time of the blood sampling (16—20 weeks of gestation). |
unexposed, sick
Untreated depressed pregnant women. |
1st and 2nd trimester, during pregnancy (anytime or not specified) | 207 / 56 | ||
| The study subjects complete web-based self-administrated structured questionnaires containing questions on ongoing medication. The medical records of the women who were on SSRI were reviewed to verify the self-reported SSRI use and to ensure that SSRI had been used during the entire pregnancy. | ||||||||
|
Heikkinen - Citalopram only 2002 |
Finland Not specified. prospective cohort |
The Turku University Hospital, Finland. | Women taking citalopram during pregnancy and lactation. |
unexposed (general population or NOS)
Women with no medication prospectively matched for confounding obstetric characteristics (age, gravidity, parity, and time and mode of delivery) at the time of delivery. |
during pregnancy (anytime or not specified), throughout pregnancy | 11 / 10 | Neurologic development not reported because not enough provided details. Ten of the women taking citalopram already had the medication at the time of conception, and one woman started the medication at 20 weeks. | |
| Blood samples (5 mL) for the analysis of plasma concentrations of citalopram and its two metabolites, desmethyl- citalopram and didesmethylcitalopram, were taken at each of the 3 visits (during pregnancy). | ||||||||
|
Heikkinen - Fluoxetine only 2003 |
Finland Not specified prospective cohort |
University of Turku and Turku University Central Hospital. Finland. | Pregnant women taking fluoxetine during pregnancy and lactation. |
unexposed (general population or NOS)
Pregnant women with no psychotropic medication was prospectively matched at the time of delivery. |
during pregnancy (anytime or not specified) | 11 / 10 | Six of the women already used fluoxetine before conception, and they used fluoxetine throughout pregnancy and lactation. Five women started taking fluoxetine later during pregnancy (ie, at 22, 27, 31, 32, and 35 weeks of gestation). | |
| Pregnant women taking fluoxetine recruited (NOS). Fluoxetine concentrations detected from the blood samples during gestation (at the last visit: 36-37 weeks of gestation). | ||||||||
|
Heinonen - Sertraline 2021 |
Sweden 2016 - 2019 randomized controlled trial |
A double-blind randomized controlled trial, a part of the MAGDALENA study. | Pregnant women randomized to sertraline group with the daily dose starting at one capsule á 25 mg and increase up to up to a dose of four capsules when lacking treatment response. |
unexposed, sick
Pregnant women randomized to placeb group. |
2nd and/or 3rd trimester, 3rd trimester | 9 / 6 | ||
| The women were either randomized to sertraline or placebo with the daily dose starting at one capsule á 25 mg. Plasma sertraline and desmethylsertraline concentrations in the mothers were measured once in the second trimester and once in the third trimester. | ||||||||
|
Heuvelman 2023 |
United Kingdom 1995 - 2017 retrospective cohort (claims database) |
The UK Clinical Practice Research Datalink, a large, ongoing database of anonymised primary care medical records for patients registered with a general practice in the United Kingdom. | Women who had initiated or continued selective serotonin reuptake inhibitor (SSRI) for the treatment of depressive symptoms during pregnancy. |
unexposed, sick
Women who did not initiate or who discontinue antidepressants during pregnancy. |
during pregnancy (anytime or not specified) | 12093 / 16330 | For ASD: Partial overlapping of Hagberg 2018 (1989 - 2011) and Heuvelman 2023 (1995 - 2017), with more uncommon study period (12 years) than common (6 years) => The 2 studies were kept. | |
| The Clinical Practice Research Datalink (CPRD) contains an extensive code list to identify the name, formulation and dose of medications, which are mandatory fields in the prescription electronic record (according to protocol). | ||||||||
|
Hogue 2017 |
USA 2007 - 2014 retrospective cohort |
A retrospective cohort study was conducted at Hillcrest Hospital, a tertiary care medical facility of the Cleveland Clinic Health System located in Mayfield Heights, Ohio. | Neonates of mothers who were treated with selective serotonin reuptake inhibitors (SSRIs) or venlafaxine during pregnancy. |
unexposed (general population or NOS)
Neonates who were not exposed to elective serotonin reuptake inhibitors (SSRIs) or venlafaxine in- utero. |
during pregnancy (anytime or not specified) | 168 / 166 | Venlafaxine less than 10% of the exposed group, thus considered as SSRI exposure. Separate analysis performed for preterm and full-term neonates. Analysis in Full term were reported here (because preterm could be a risk factor of the considered outcomes). | |
| Review of electronic medical records. Each participant’s obstetric visits for prenatal care, medication histories, and other inpatient notes were reviewed to ensure the neonate was exposed to one of the study medications during pregnancy. | ||||||||
|
Hutchison a 2019 |
Canada Not specified. prospective cohort |
A longitudinal cohort study of women referred from the British Columbia Women’s Hospital and Health Centre, community midwife clinics or family physician practices in the greater Vancouver metropolitan area. | Pregnant women treated with selective serotonin reuptake inhibitor (SSRI) during pregnancy. |
unexposed, sick
Pregnant women with a range of mood symptoms at recruitment and over the subsequent 6 years, not treated by selective serotonin reuptake inhibitor (SSRI). |
during pregnancy (anytime or not specified) | 42 / 74 | Child Daily Macronutrients, Sugar, and Sodium Intake at 6 Years and Continuous variables not reported here (excepted for Gross motor scale at 10 months). | |
| Not specified (mothers recruited during their second trimester of pregnancy). | ||||||||
|
Hutchison b 2019 |
Canada Not specified prospective cohort |
A longitudinal cohort study conducted in University of British Columbia Ethics Board and the Children's and Women's Health Centre of British Columbia; | Infants of Selective Serotonin Reuptake Inhibitor (SSRI)-treated mothers had a diagnosed mood disorder and had started taking medications based on clinical need. |
unexposed, sick
Infants of women without Serotonin Reuptake Inhibitor (SSRI) use but who had a range of mood symptoms at the time of recruitment and over the subsequent 6 years. |
during pregnancy (anytime or not specified) | 51 / 88 | ||
| Mothers recruited during their second trimester of pregnancy. | ||||||||
|
Huybrechts (Controls unexposed, NOS) 2014 |
USA 2000 - 2007 cohort |
Cohort study nested in the nationwide Medicaid Analytic eXtract. | Pregnant women who have had exposure to selective serotonin-reuptake inhibitors (SSRIs) with the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women without exposure to antidepressants during the first trimester. |
1st trimester | 46144 / 885115 | Exclusion of pregnancies with a diagnosis of a chromosomal abnormality and pregnancies in which the mother had been treated with known teratogens during the first trimester (i.e., lithium, antineoplastic agents, retinoids, and thalidomide). | |
| The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions. | ||||||||
|
Huybrechts (Controls unexposed, NOS) 2015 |
USA 2000 – 2010 retrospective cohort (claims database) |
Cohort study nested in the Medicaid Analytic eXtract (MAX). | Pregnant women who filled at least 1 prescription for a selective serotonin reuptake inhibitors (SSRI) from 90 days before delivery through delivery. |
unexposed (general population or NOS)
Pregnant women without exposure to antidepressants at any time during pregnancy. |
3rd trimester | 102179 / 3660380 | Women exposed to both SSRIs and non-SSRIs were excluded from the cohort. | |
| The Medicaid Analytic eXtract (MAX) data set records health care use including filled outpatient medication prescriptions. | ||||||||
|
Huybrechts (Controls unexposed, sick) 2015 |
USA 2000 – 2010 retrospective cohort (claims database) |
Cohort study nested in the Medicaid Analytic eXtract (MAX). | Pregnant women who filled at least 1 prescription for a selective serotonin reuptake inhibitors (SSRI) from 90 days before delivery through delivery. |
unexposed, sick
Pregnant women with a depression diagnosis without exposure to antidepressants at any time during pregnancy. |
3rd trimester | 65316 / 657515 | Women exposed to both SSRIs and non-SSRIs were excluded from the cohort. | |
| The Medicaid Analytic eXtract (MAX) data set records health care use including filled outpatient medication prescriptions. | ||||||||
|
Huybrechts (Controls unexposed, sick) 2014 |
USA 2000 - 2007 cohort |
Cohort study nested in the nationwide Medicaid Analytic eXtract. | Pregnant women who have had exposure to selective serotonin-reuptake inhibitors (SSRIs) with the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with a diagnosis of depression without exposure to antidepressants during the first trimester. |
1st trimester | 36778 / 180564 | Exclusion of pregnancies with a diagnosis of a chromosomal abnormality and pregnancies in which the mother had been treated with known teratogens during the first trimester (i.e., lithium, antineoplastic agents, retinoids, and thalidomide). | |
| The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions. | ||||||||
|
Isohata 2025 |
Japan 2019 - 2023 retrospective cohort |
Kitasato University Hospital, a tertiary care facility, Sagamihara, Kanagawa, Japan. | Pregnancies complicated by maternal mental disorders that have taken Selective serotonin reuptake inhibitors (SSRIs) at the time of admission for delivery. |
unexposed, sick
Pregnancies complicated by maternal mental disorders that have not taken psychotropic medications at the time of admission for delivery. |
days before delivery | 42 / 177 | Psychotropic medications included: antipsychotics (typical or atypical), antidepressants, anti-anxiety, anti-epileptic and slee-inducing. | |
| Not specified. | ||||||||
|
Jackson 2024 |
U.S.A 2019 - 2022 retrospective cohort (claims database) |
Inpatient electronic medical record system (Sunrise Clinical Manager, Allscripts Corp., Chicago, IL) of 7 hospitals within a large academic health system in New York. | Prenatal exposure to a monotherapy of selective serotonin reuptake inhibitors (SSRIs: escitalopram, fluoxetine, sertraline). |
unexposed, disease free
No prenatal exposure to selective serotonin reuptake inhibitors (SSRIs: escitalopram, fluoxetine, sertraline). |
during pregnancy (anytime or not specified) | 2106 / 105000 | ||
| Medication exposure was determined by its presence or absence in the medication reconciliation document completed during hospital admission. | ||||||||
|
Jaeger 2019 |
USA 2014 - 2017 retrospective cohort |
The US Military Healthcare System (MHS), USA. | Pregnant women using Selective Serotonin Reuptake Inhibitor (SSRI) during the 3 months before and at each trimester of pregnancy. |
unexposed (general population or NOS)
Pregnant women not using Selective Serotonin Reuptake Inhibitor (SSRI) during pregnancy. |
2nd trimester, 3rd trimester | -9 / -9 | ||
| Analysis of insurance records (no other details). | ||||||||
|
Jensen b 2013 |
Denmark 1996 - 2006 population based cohort retrospective |
Nationwide register study linking data from the Medical Birth Register, the Psychiatric Central Register, and a prescription database. | Live births whose mother redeemed a prescription for selective serotonin reuptake inhibitors during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Live births whose mother without a diagnosis of depression as well as to antidepressants. |
during pregnancy (anytime or not specified) | 7208 / 628898 | ||
| The Medicinal Product Statistics which is a nationwide prescription database containing individual information on all prescriptions filled at all Danish pharmacies. | ||||||||
|
Jimenez-Solem (Controls unexposed, NOS) 2012 |
Denmark 1997 - 2009 population based cohort retrospective |
Register-based retrospective nationwide cohort study, using the Danish Medical Birth Registry. | Pregnancies with a continuous exposure to a selective serotonin reuptake inhibitor (SSRI), at least 1 month before conception until day 84 of pregnancy (last day of the first trimester). |
unexposed (general population or NOS)
Pregnancies with no exposure to a selective serotonin reuptake inhibitor (SSRI) during pregnancy. |
1st trimester | 4183 / 843797 | Overlapping: this study included data published by Kornum 2010. Overlapping: Data related to Major and cardiac malformations not reported because an overlapping Furu 2015 a larger study including data from 5 nordic countries, including Denmark. | |
| The drug redemptions were identified using the Register of Medicinal Product Statistics which has recorded drugs dispensed from Danish pharmacies. | ||||||||
|
Jimenez-Solem (Controls unexposed, sick) 2012 |
Denmark 1997 - 2009 population based cohort retrospective |
Register-based retrospective nationwide cohort study, using the Danish Medical Birth Registry. | Pregnancies with a continuous exposure to a selective serotonin reuptake inhibitor (SSRI), at least 1 month before conception until day 84 of pregnancy (last day of the first trimester). |
unexposed, sick
Pregnancies with paused exposure during pregnancy (an SSRI 3-12 months before conception and 1-12 months after giving birth but with no exposure to an SSRI between 3 months before conception to 1 month after giving birth). |
1st trimester | 4183 / 806 | Overlapping: this study included data published by Kornum 2010. Overlapping: Data related to Major and cardiac malformations not reported because an overlapping Furu 2015 a larger study including data from 5 nordic countries, including Denmark. | |
| The drug redemptions were identified using the Register of Medicinal Product Statistics which has recorded drugs dispensed from Danish pharmacies. | ||||||||
|
Jordan 2016 |
Norway, Wales and Denmark. 2000 - 2010 retrospective cohort (registry) |
Three population-based EUROCAT congenital anomaly registries- Norway, Wales and Funen, Denmark. | Prescription of selective serotonin reuptake inhibitors (SSRIs) in the 91 days either side of the 1st day of last menstrual period (LMP). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
No prescription of selective serotonin reuptake inhibitors (SSRIs) during pregancy. |
3 months or more before pregnancy or1st trimester | 12962 / 506155 | Number of cases and controls changed according to the considered anomaly. Overlapping: Outcomes published in Wemakor 2015 (largest study) and Given 2017 (Gastroschisis) not reported here. Overlapping: Jordan 2016 included results of Knudsen 2014. | |
| Anomalies registries were linked with prescription and healthcare databases covering their source populations (Danish national Prescription and Patient register; Norway National Prescription Database; and Wales’ health and social care linked electronic databank). | ||||||||
|
Källén 2007 |
Sweden 1995 - 2004 population based cohort retrospective |
The Swedish Medical Birth Register, the Register of Congenital Malformations, and the Hospital Discharge Register. | Pregnant women who reported the use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy. |
unexposed (general population or NOS)
The total population. |
early pregnancy | 6481 / 873876 | 179 women reported the additional use of a non-SSRI antidepressant (2.8%) => >90% reported SSRI only => considered as SSRI only. Overlapping: individual malformations included in Reis 2010 not reported here. | |
| Drug information was obtained from routine midwife interviews at the first antenatal care center visit (in 90% before the end of week 12) using a standardized form. | ||||||||
|
Källén (Controls exposed to TCA) 2004 |
Sweden 1995 - 2001 population based cohort retrospective |
The Swedish Medical Birth Registry. | Infants whose mothers received selective serotonin reuptake inhibitors (SSRIs) after the first antenatal care center visit. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants whose mothers received Tricyclic drugs after the first antenatal care center visit. (This is a subgroup of exposure among the whole exposed group considered in the study). |
late pregnancy | 558 / 395 | Overlapping: Preterm, Low birth weight, SGA, LGA; hypoglycemia, convlusions and respiratory problems not reported here because these data (Sweden 1995-2001) have been updated by larger studies: Reis 2010 (1995-2007) and Lennestal (1995-2004). | |
| Data on first-trimester exposures are obtained by midwife interviews at the first antenatal care visit (usually week 10-12), while data on later exposures are obtained from the copies of the medical records of the antenatal care. | ||||||||
|
Källén (Controls unexposed, NOS) 2004 |
Sweden 1995 - 2001 population based cohort retrospective |
The Swedish Medical Birth Registry. | Infants whose mothers received selective serotonin reuptake inhibitors (SSRIs) after the first antenatal care center visit. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
All infants in the registry. |
late pregnancy | 558 / 581787 | Overlapping: Preterm, Low birth weight, SGA, LGA; hypoglycemia, convlusions and respiratory problems not reported here because these data (Sweden 1995-2001) have been updated by larger studies: Reis 2010 (1995-2007) and Lennestal (1995-2004). | |
| Data on first-trimester exposures are obtained by midwife interviews at the first antenatal care visit (usually week 10-12), while data on later exposures are obtained from the copies of the medical records of the antenatal care. | ||||||||
|
Kieler 2012 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2007 population based cohort retrospective |
Population based cohort study using data from the national health registers from the five Nordic countries. | A filled prescription of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed (general population or NOS)
No filled prescription of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
2nd and/or 3rd trimester, 3 months or more before pregnancy or1st trimester | 30115 / 1588140 | Overlapping: this study included results of Kallen 2008 and Norby 2016. | |
| The prescription registers. | ||||||||
|
Kildegaard 2025 |
- |
-
|
-9 / -9 | Risk of disorders of gut-brain interaction in children (DGBI) (functional nausea and vomiting, functional abdominal pain disorders, functional diarrhea, and functional constipation, ...) => outcome indexed but not reported in metaPreg. | ||||
|
Kivistö 2016 |
Finland 2002 - 2012 retrospective cohort |
Retrospective study conducted at the Kuopio University Hospital. | Pregnant women that used only Selective Serotonin Reuptake Inhibitors (SSRI) during pregnancy. |
unexposed (general population or NOS)
Pregnant women not using any antidepressant medication. |
during pregnancy (anytime or not specified) | 358 / 24402 | Pre-eclampsia and Gestational diabetes not reported because not sure that exposure occurred before outcome. | |
| The data were gathered retrospectively from the hospital birth register. | ||||||||
|
Klieger-Grossmann - Escitalopram 2012 |
Canada, Switzerland and Italy Not specified. prospective cohort |
The Motherisk Program in Toronto, the Swiss Teratogen Information Service, and the Florence Teratogen Information Service. | Pregnant women exposed to escitalopram during pregnancy. |
unexposed (general population or NOS)
Pregnant women who called for nonteratogenic exposures such as acetaminophen, antibiotics, anti- histamines, and so on. |
1st trimester, during pregnancy (anytime or not specified), late pregnancy | 213 / 212 | The 21 exposures to escitalopram that were part of a larger prospective study from Motherisk (Einarson 2009) were excluded from this study. Results versus other antidepressants (SSRIs, venlafaxine, mirtazapine...) not reported => inadequate control group. | |
| During the initial telephone contact, details of exposure and concurrent exposures were recorded using a standardized questionnaire. Details regarding the exposure included duration and timing in pregnancy, as well as dose, frequency, and indication for drug use. | ||||||||
|
Knickmeyer 2014 |
USA Not specified retrospective cohort |
University of North Carolina at Chapel Hill, USA. | Children of mothers with depression and Selective serotonin reuptake inhibitors (SSRIs) use during pregnancy. |
unexposed, disease free
Children of mothers without Selective serotonin reuptake inhibitors (SSRIs) use during pregnancy. |
during pregnancy (anytime or not specified), early pregnancy, throughout pregnancy | 33 / 66 | 'Use of a psychiatric drug other than an SSRI was an exclusion criterion for the current analysis with the exception of trazodone, low-dose benzodiazepines, and psychostimulants.' | |
| Exposure during pregnancy confirmed by maternal self-report and medical record review. Self-report was in response to an oral interview. | ||||||||
|
Kolding (Controls unexposed, disease free) 2021 |
Denmark 2007 - 2014 population based cohort retrospective |
Five nationwide registries and databases: the Danish Fetal Medicine Database, the Danish National Patient Registry, the Danish Medical Birth Registry and the Danish Health Services Prescription Database. | Pregnant women with two or more redeemed prescriptions of Selective serotonin reuptake inhibitors (SSRIs) from 28 days before through 70 days after the conception date. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnant women with absence of redemptions for an antidepressant in the same time window, combined with absence of former use. |
1st trimester | 2767 / 353581 | 'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.' SSRI: Fluoxetine (N06AB03), citalopram (N06AB04), paroxetine (N06AB05), sertraline (N06AB06), fluvoxamine (N06AB08), escitalopram (N06AB10) | |
| Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database. | ||||||||
|
Kolding (Controls unexposed, sick) 2021 |
Denmark 2007 - 2014 population based cohort retrospective |
Five nationwide registries and databases: the Danish Fetal Medicine Database, the Danish National Patient Registry, the Danish Medical Birth Registry and the Danish Health Services Prescription Database. | Pregnant women with two or more redeemed prescriptions of Selective serotonin reuptake inhibitors (SSRIs) from 28 days before through 70 days after the conception date. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with untreated- or well treated depression or anxiety without antidepressant use in the pregnancy (one or more redeemed prescription of an antidepressant from 365 to 183 days preconception and no redemptions between 182 days preconception through the first trimester). |
1st trimester | 2767 / 6326 | 'Pregnancies with fetal chromosomal abnormalities were excluded regardless of presence of other malformations.' | |
| Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database. | ||||||||
|
Kragholm 2018 |
Denmark 2005 - 2008 population based cohort retrospective |
A population-based case-cohort study using Danish nationwide birth. | Offspring of mothers on selective serotonin reuptake inhibitors (SSRIs) during pregnancy (from the beginning of the pregnancy to the end of the pregnancy in sensitivity analyses). |
unexposed, sick
Offspring of mothers on selective serotonin reuptake inhibitors (SSRIs) before 90 days prior to conception but not during the 90-day period before or during the actual pregnancy period. |
1st and 2nd trimester, 1st trimester, 2nd and/or 3rd trimester, 2nd trimester, 3 months (or more) before pregnancy or during pregnancy, 3rd trimester, during pregnancy (anytime or not specified), throughout pregnancy | 3314 / 3536 | ||
| Data on selective serotonin reuptake inhibitors exposure were obtained from the Danish Prescription Registry, which contains data on redeemed drug prescriptions from all Danish pharmacies. | ||||||||
|
Kulin 1998 |
USA and Canada Not specified. prospective cohort |
Nine Teratology Information Service centers in the United States and Canada. | Pregnant women who were counseled during pregnancy following exposure to a new selective serotonin reuptake inhibitors (SSRIs ; fluvoxamine, paroxetine, and sertraline) during the first trimester of pregnancy for depression. |
unexposed (general population or NOS)
Pregnant women counseled after exposure to nonteratogenic agents, randomly selected. |
1st trimester | 267 / 267 | ||
| During the initial interview at the time of exposure, women were asked notably about SSRI dose schedule and length of therapy and other drug therapy. | ||||||||
|
Latendresse 2011 |
USA March - Nov 2007 prospective cohort |
3 community prenatal clinics in collaboration with University of Utah | Use of Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy to treat depression and/or anxiety. |
unexposed (general population or NOS)
No use of Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy. |
during pregnancy (anytime or not specified) | 13 / 87 | ||
| The use of medication for mental health conditions was ascertained in 2 ways. First, 1 item included in the participant questionnaire conducted during pregnancy. Second, the prenatal and birth records were reviewed for any documentation of medication use. | ||||||||
|
Laugesen 2013 |
Denmark 1996 - 2009 population based cohort retrospective |
Nationwide Danish medical registries | Children born to mother with redemption of a Selective serotonin reuptake inhibitors (SSRI) prescription by the mother 30 days prior to or during pregnancy. (This is a subgroup of exposure among the whole exposed group considered). |
unexposed (general population or NOS)
Children born to mother who had never redeemed a prescription on antidepressants. |
during pregnancy (anytime or not specified) | 11721 / 816792 | ||
| Prescription identified through the Danish National Prescription. | ||||||||
|
Lee (Controls exposed to TCAs) 2025 |
China 2003 - 2018 retrospective cohort (claims database) |
The Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority, Hong Kong. | Women filling at least one prescription of any selective serotonin reuptake inhibitors (SSRI) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery. |
exposed to other treatment, sick
Women filling at least one prescription of any tricyclic antidepressants (TCA) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery. |
during pregnancy (anytime or not specified) | 1465 / 613 | ||
| The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records. | ||||||||
|
Lee (Controls unexposed, general pop) 2024 |
Taiwan 2004 - 2016 population based cohort retrospective |
The National Health Insurance Research Database (NHIRD) in Taiwan. | Liveborn infants born to mothers who had at least one selective serotonin reuptake inhibitors (SSRIs - N06AB) dispensation during the defined periods before- and after-pregnancy and throughout pregnancy. |
unexposed (general population or NOS)
Liveborn infants born to mothers who had not received any antidepressant dispensation during the defined periods before- and after-pregnancy and throughout pregnancy. |
1st and 2nd trimester, 2nd and/or 3rd trimester, 3 months or more before pregnancy or1st trimester | 29739 / 2245689 | Authors provided 3 periods of exposure: 1st trimester (from 90 days before pregnancy to 90 days after conception); 2nd trimester (from conception to end of 2nd trimester)... Use of the 2nd one (larger period during pregnancy). | |
| Maternal exposures were identified in dispensation records obtained from the Details of Ambulatory Care Orders dataset of the National Health Insurance Research Database, which includes all medication dispensations and accompanying prescriptions for all outpatient visits in Taiwan. | ||||||||
|
Lee (Controls unexposed, general pop) 2025 |
China 2003 - 2018 retrospective cohort (claims database) |
The Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority, Hong Kong. | Women filling at least one prescription of any selective serotonin reuptake inhibitors (SSRI) only during pregnancy, that is the period between the date of the last menstrual period and the date of delivery. |
unexposed (general population or NOS)
Women who were not prescribed with any antidepressant during index pregnancy. |
during pregnancy (anytime or not specified) | 1465 / 463440 | ||
| The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records. | ||||||||
|
Lee (Controls unexposed, sibling) 2024 |
Taiwan 2004 - 2016 population based cohort retrospective |
The National Health Insurance Research Database (NHIRD) in Taiwan. | Liveborn infants born to mothers who had at least one selective serotonin reuptake inhibitors (SSRIs - N06AB) dispensation during the defined periods before- and after-pregnancy and throughout pregnancy. |
sibling
Siblings born to the same mother who were not exposed to antidepressants during pregnancy and antidepressant-exposed individuals. |
1st and 2nd trimester, 2nd and/or 3rd trimester, 3 months or more before pregnancy or1st trimester | 2458 / 2948 | Authors provided 3 periods of exposure: 1st trimester (from 90 days before pregnancy to 90 days after conception); 2nd trimester (from conception to end of 2nd trimester)... Use of the 2nd one (larger period during pregnancy). | |
| Maternal exposures were identified in dispensation records obtained from the Details of Ambulatory Care Orders dataset of the National Health Insurance Research Database, which includes all medication dispensations and accompanying prescriptions for all outpatient visits in Taiwan. | ||||||||
|
Lennestal 2007 |
Sweden 1995 - 2004 population based cohort retrospective |
The Medical Birth Register, the Register of Congenital Malformations and the Hospital Discharge Register. | Women who reported the use of Selective serotonin reuptake inhibitor (SSRI) drugs during pregnancy (early and/or late pregnancy). |
unexposed (general population or NOS)
All deliveries in the register. |
early pregnancy, late pregnancy | -9 / 873876 | Methods completed with publication of Kallen 2007 because authors mentioned that 'Data for SSRI from Kallen 2007'. Malfo, LBW, preterm, SGA, LGA: overlapping with Kallen 2007 and Reis 2010 (1995 - 2007). | |
| Data on maternal use of drugs were obtained through interviews performed at the first antenatal care visit (early exposure) and was supplemented with information on drugs prescribed by the antenatal care during the remaining part of the pregnancy (late exposure). | ||||||||
|
Levinson-Castiel 2006 |
Israel 2002 - 2004 retrospective cohort |
The Rabin Medical Center in Israel, a tertiary care facility housing a neonatology department. | Neonates exposed to selective serotonin reuptake inhibitors (SSRIs) in utero during the entire pregnancy or at least during the third trimester. |
unexposed, disease free
Neonates not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero, born to healthy mothers. |
3rd trimester | 60 / 60 | Maternal intake of SSRIs during pregnancy, including fluoxetine, paroxetine, citalopram, sertraline, and the serotonin-noradrenaline reuptake inhibitor venlafaxine. Of the 60 exposed pregnancies, only 2 exposed to venlafaxine (3.3%) => considered as SSRI. | |
| The infants were identified from the delivery room records as they arrived at the nursery or from a medical history form completed by all mothers at admittance to the nursery. This form included notably type, dosage, and duration of treatment with SSRIs or other drugs. | ||||||||
|
Levy 2020 |
Israel Jan - June 2019 retrospective cohort |
The university-affiliated tertiary center (the Edith Wolfson Medical Center), Israel | Maternal Selective Serotonin Reuptake Inhibitors (SSRIs) use throughout pregnancy. |
unexposed (general population or NOS)
No Maternal Selective Serotonin Reuptake Inhibitors (SSRIs) use during pregnancy. |
throughout pregnancy | 82 / 82 | ||
| The electronic files of women were reviewed. | ||||||||
|
Liu 2017 |
Denmark 1998 - 2012 population based cohort retrospective |
Data from Danish national registers. | A prescription of Selective serotonin reuptake inhibitors (SSRIs) monotherapy dispensed on any date from one month before pregnancy until delivery. (This is a subgroup of exposure among the whole exposed group considered). |
unexposed, sick
Antidepressant discontinuation (use before but not during pregnancy). |
during pregnancy (anytime or not specified) | 16154 / 30079 | For emotional disorders: Overlapping: Liu 2017 (1998 - 2012) included in Bliddal 2023 (1997 - 2015) => Only Bliddal 2023 used here because more exposed pregnancies. For ASD: use of Liu 2017 rather Sorensen 2013 (more pregnancies in Liu 2017). | |
| Information on antidepressant use came from the Danish National Prescription Registry, that covers all prescriptions dispensed in Denmark since 1995. | ||||||||
|
Liu 2015 |
Denmark 1996 - 2007 population based cohort retrospective |
Linkage of several national registers in Denmark, including the Danish Medical Birth Registry (DMBR), the Danish Psychiatric Central Register and the Danish National Patient Register. | Children born to mothers who had prenatal depression and who used Selective serotonin reuptake inhibitors (SSRIs) only during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children born to mothers who had prenatal depression and who did not take antidepressants during pregnancy. |
1st trimester, 2nd and/or 3rd trimester, during pregnancy (anytime or not specified) | 7186 / 12476 | Selective serotonin reuptake inhibitors (SSRIs, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine [N06AB03-10]). | |
| Data on maternal or paternal antidepressants dispensed 1 year before or during the index pregnancy and dispensing date were extracted from the Danish National Prescription Registry. | ||||||||
|
Lund (Controls unexposed, disease free) 2009 |
Denmark 1989 - 2006 prospective cohort |
The Aarhus Birth Cohort, a prospective cohort study conducted in Department of Obstetrics, Aarhus University Hospital, Aarhus, Denmark. | Pregnant women reported treatment with selective serotonin reuptake inhibitor (SSRIs) during pregnancy. |
unexposed, disease free
Pregnant women without a history of psychiatric illness. |
during pregnancy (anytime or not specified) | 329 / 51770 | Among the 329 women with SSRI intake, 38 (88%) also used another psychotropic drug during pregnancy. | |
| During the early second trimester, women were asked to complete a self-administered questionnaire, including information on medical treatment during pregnancy. Exposure also reported in the coding sheet filled in by the midwife at delivery. | ||||||||
|
Lund (Controls unexposed, sick) 2009 |
Denmark 1989 - 2006 prospective cohort |
The Aarhus Birth Cohort, a prospective cohort study conducted in Department of Obstetrics, Aarhus University Hospital, Aarhus, Denmark. | Pregnant women reported treatment with selective serotonin reuptake inhibitor (SSRIs) during pregnancy. |
unexposed, sick
Pregnant women who were not treated with selective serotonin reuptake inhibitor (SSRIs) but had a history of psychiatric illness. |
during pregnancy (anytime or not specified) | 329 / 4902 | Among the 329 women with SSRI intake, 38 (88%) also used another psychotropic drug during pregnancy. | |
| During the early second trimester, women were asked to complete a self-administered questionnaire, including information on medical treatment during pregnancy. Exposure also reported in the coding sheet filled in by the midwife at delivery. | ||||||||
|
Lupattelli (Controls exposed to TCA) 2017 |
Norway 1999 - 2008 prospective cohort |
The Norwegian Mother and Child Cohort (the MoBa study), a prospective population‐based study, and the Medical Birth Registry of Norway | Depressed pregnant women that reported use of selective serotonin reuptake inhibitors (SSRIs) monotherapy during pregnancy. |
exposed to other treatment, sick
Depressed pregnant women that reported use of tricyclic antidepressants (TCAs) monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 654 / 21 | 'Women on antidepressant polytherapy, ie, exposed to multiple antidepressant groups in pregnancy, were excluded' | |
| Data about antidepressant exposure were gathered prospectively from 2 self‐completed questionnaires at Gestational weeks 17 (Q1) and 30 (Q3). Women reported the name of the medication taken along with timing of use (6 months before pregnancy and during pregnancy by 4‐week intervals). | ||||||||
|
Lupattelli (Controls unexposed, disease free) 2014 |
Norway 1999 - 2006 prospective cohort |
The Norwegian Mother and Child Cohort Study (MoBa) and records in the Medical Birth Registry of Norway (MBRN). | Use of Selective serotonin reuptake inhibitors (SSRIs) or Serotonin–norepinephrine reuptake inhibitors (SNRIs) during pregnancy. |
unexposed, disease free
No reported use of antidepressants during pregnancy and no presence of depressive symptoms at gestational weeks 17 and/or 30. |
1st trimester, 2nd trimester, late pregnancy | 527 / 55411 | Venlafaxine and duloxetine represents less than 10% (11/123) of the SSRI/SNRI exposures during last part of pregnancy=> Considered as SSRI exposure. | |
| Information about type and timing of antidepressant use was retrieved from pregnant women self-administered questionnaires (Q1, Q3, and Q4) completed during and after pregnancy | ||||||||
|
Lupattelli (Controls unexposed, sick) 2017 |
Norway 1999 - 2008 prospective cohort |
The Norwegian Mother and Child Cohort (the MoBa study), a prospective population‐based study, and the Medical Birth Registry of Norway | Depressed pregnant women that reported use of selective serotonin reuptake inhibitors (SSRIs) monotherapy during pregnancy. |
unexposed, sick
Depressed pregnant women nonmedicated. |
1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified) | 654 / 5106 | 'Women on antidepressant polytherapy, ie, exposed to multiple antidepressant groups in pregnancy, were excluded' | |
| Data about antidepressant exposure were gathered prospectively from 2 self‐completed questionnaires at Gestational weeks 17 (Q1) and 30 (Q3). Women reported the name of the medication taken along with timing of use (6 months before pregnancy and during pregnancy by 4‐week intervals). | ||||||||
|
Lupattelli (Controls unexposed, sick) 2014 |
Norway 1999 - 2006 prospective cohort |
The Norwegian Mother and Child Cohort Study (MoBa) and records in the Medical Birth Registry of Norway (MBRN). | Use of Selective serotonin reuptake inhibitors (SSRIs) or Serotonin–norepinephrine reuptake inhibitors (SNRIs) during pregnancy. |
unexposed, sick
No exposure to antidepressants but presence of depressive symptoms at both gestational weeks 17 and 30. |
1st trimester, 2nd trimester, late pregnancy | 527 / 1282 | Venlafaxine and duloxetine represents less than 10% (11/123) of the SSRI/SNRI exposures during last part of pregnancy=> Considered as SSRI exposure. | |
| Information about type and timing of antidepressant use was retrieved from pregnant women self-administered questionnaires (Q1, Q3, and Q4) completed during and after pregnancy | ||||||||
|
Lyn 2023 |
Australia 2020 - 2021 retrospective cohort |
Royal Women’s Hospital or Women’s and Children’s Clinical Institute, Melbourne, Australia. | Pregnant women who reported selective serotonin reuptake inhibitor (SSRI) use in their pregnancy. |
unexposed (general population or NOS)
Pregnant women who did not report antidepressant use in their pregnancy. |
during pregnancy (anytime or not specified) | 130 / 259 | Sertraline is the most common SSRI used in pregnancy (56%). | |
| Not specified. | ||||||||
|
Malm 2011 |
Finland 1996 - 2006 population based cohort retrospective |
An ongoing national joint project, Drugs and Pregnancy, based on three national health registers: The Medical Birth Register and the Register of Congenital Malformations and the Drug Reimbursement Register. | Offspring of mothers with at least one purchase of one or more selective serotonin reuptake inhibitor drugs during the period of 1 month before pregnancy and first trimester. |
unexposed (general population or NOS)
Offspring of mothers without purchase of one or more selective serotonin reuptake inhibitor drugs. |
1st trimester | 6881 / 618727 | Overlapping: Major malformations and cardiovascular malformations (excepted ASV, VSD and transpo of great vessels) updated in a larger study published by Furu 2015 (1996-2010). Thus only the not updated malformations are reported here. | |
| The Drug Reimbursement Register that contains data on 98% of reimbursed prescription drug purchases. | ||||||||
|
Malm (Controls unexposed, disease free) 2015 |
Finland 1996 - 2010 population based cohort retrospective |
A population-based prospective birth cohort study using national register data. | Pregnant women who purchased selective serotonin reuptake inhibitors (SSRIs) during the period from 30 days before the beginning of gestation until the end of pregnancy. |
unexposed, disease free
Pregnant women who had no psychiatric diagnosis and no exposure to selective serotonin reuptake inhibitors (SSRIs). |
during pregnancy (anytime or not specified) | 15729 / 31394 | Overlapping: Data related to PPHN and Major malformations not reported because an overlapping with Kieler 2012 and Furu 2015, 2 larger studies including data from 5 nordic countries, including Finland. Overlapping: Malm 2015 included Malm 2005. | |
| The Drug Reimbursement Register which collect data on prescription drug purchases. Over- the-counter drugs and medications administered to institutionalized persons are not included. | ||||||||
|
Malm (Controls unexposed, disease free) 2016 |
Finland 1996 - 2010 population based cohort retrospective |
A national population-based, prospective cohort study design, Finland. | Pregnant women who had one or more purchases of Selective serotonin reuptake inhibitors (SSRIs) during the period from 30 days before pregnancy until the end of pregnancy. |
unexposed, disease free
Pregnant women with neither purchases of antidepressants nor antipsychotics, and no depression or related psychiatric disorder at any time prior to or during pregnancy. |
during pregnancy (anytime or not specified) | 15729 / 31394 | ||
| The Drug Reimbursement Register that collects data on prescription drug purchases and was used to identify the study groups. | ||||||||
|
Malm (Controls unexposed, sick) 2015 |
Finland 1996 - 2010 population based cohort retrospective |
A population-based prospective birth cohort study using national register data. | Pregnant women who purchased selective serotonin reuptake inhibitors (SSRIs) during the period from 30 days before the beginning of gestation until the end of pregnancy. |
unexposed, sick
Pregnant women who had a psychiatric diagnosis related to SSRIs but who had no purchases of antidepressants or antipsychotics from 3 months before the beginning of gestation until delivery. |
during pregnancy (anytime or not specified) | 15729 / 9652 | Overlapping: Data related to PPHN and Major malformations not reported because an overlapping with Kieler 2012 and Furu 2015, 2 larger studies including data from 5 nordic countries, including Finland. Overlapping: Malm 2015 included Malm 2005. | |
| The Drug Reimbursement Register which collect data on prescription drug purchases. Over- the-counter drugs and medications administered to institutionalized persons are not included. | ||||||||
|
Malm (Controls unexposed, sick) 2016 |
Finland 1996 - 2010 population based cohort retrospective |
A national population-based, prospective cohort study design, Finland. | Pregnant women who had one or more purchases of Selective serotonin reuptake inhibitors (SSRIs) during the period from 30 days before pregnancy until the end of pregnancy. |
unexposed, sick
Pregnant women who had a diagnosis of depression or other psychiatric disorder, from one year before pregnancy until discharge (≤ 3 weeks) from hospital after delivery, and no purchases of antidepressants or antipsychotics from three months before until the end of pregnancy. |
during pregnancy (anytime or not specified) | 15729 / 9651 | ||
| The Drug Reimbursement Register that collects data on prescription drug purchases and was used to identify the study groups. | ||||||||
|
Man (Controls exposed to antipsychotics) 2017 |
Hong Kong 2001 - 2009 retrospective cohort (claims database) |
The Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System (CDARS). | Children whose mothers used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children whose mothers used antipsychotics (non SSRIs users) during pregnancy. |
during pregnancy (anytime or not specified) | 425 / -9 | Number of children exposed to SSRI considered not clearly stated (425 SSRI only and/or 266 SSRI in combination). Number of children exposed to antipsychotics (non SSRIs users) not provided. | |
| Antidepressant use in mothers was extracted from the prescribing and dispensing records in the Clinical Data Analysis and Reporting System (CDARS). | ||||||||
|
Man (Controls unexposed, NOS) 2017 |
Hong Kong 2001 - 2009 retrospective cohort (claims database) |
The Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System (CDARS). | Children whose mothers used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children of mothers who were non-gestational users (a combined group of never users and preconception users). |
1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified) | 691 / 189002 | The non-gestational users marginally composed of mothers that had discontinued treatment before pregnancy (n=1486). Number of children exposed to SSRI considered not clearly stated (425 SSRI only and/or 266 SSRI in combination). | |
| Antidepressant use in mothers was extracted from the prescribing and dispensing records in the Clinical Data Analysis and Reporting System (CDARS). | ||||||||
|
Manakova 2011 |
Czech Republic 2002 - 2009 prospective cohort |
Czech Teratology Information Service (CZTIS) | Pregnant women exposed to Selective serotonin reuptake inhibitors (SSRI). |
unexposed (general population or NOS)
Pregnant women exposed to non-teratogenic and non-psychotropic substances (mainly to hormonal contraception, common antibiotics, vaccine, paracetamol or antihistaminics). |
1st trimester | 43 / 85 | 'Ten cases were included in both groups exposed to both, SSRI and APD (new psychotropic drugs).' | |
| The details of exposure were obtained after enrollment in the study. The data collection at the first contact and follow up were obtained by phone call or by written e-mail questionnaire. | ||||||||
|
Margulis 2013 |
United Kingdom 1996 - 2010 retrospective cohort (claims database) |
The Clinical Practice Research Datalink’s Mother Baby Link (CPRD), formerly called GPRD, an automated health care database. | Pregnant women who had one or more therapy episodes for Selective serotonin reuptake inhibitor (SSRIs) overlapping with the first trimester of pregnancy and did not have therapy episodes for other antidepressants. |
unexposed (general population or NOS)
Pregnant women with no antidepressant therapy episodes in the 3 months before pregnancy or in the first or second trimester of pregnancy. |
1st trimester | 3046 / 8991 | Primary outcomes: cardiac malformations at 1 year. Thus results at 6 years not reported here. | |
| The Clinical Practice Research Datalink (CPRD), formerly called GPRD, an automated health care database that contains prescriptions. Prescriptions with fields for the patient and product identifiers, and dose are issued electronically. | ||||||||
|
Marks - Sertraline (Controls exposed to Bupropion) 2021 |
USA 2010 - 2019 retrospective cohort |
Electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis, USA. | Pregnant women with one (or more) prescription of Sertraline written during the time period studied. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women with one (or more) prescription of Bupropion written during the time period studied. |
during pregnancy (anytime or not specified) | 1653 / 406 | This study assessed several SSRIs => data of all SSRI substances cannot be added (to keep adjustment). Thus, in order to avoid redundancy of control, only the substance with the higher number of exposure was used in the meta-analysis (i.e sertraline). | |
| Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis. | ||||||||
|
Marks - Sertraline (Controls unexposed, sick) 2021 |
USA 2010 - 2019 retrospective cohort |
Electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis, USA. | Pregnant women with one (or more) prescription of Sertraline during the third trimester exposure. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women who took an antidepressant at some point during pregnancy but did not have a prescription for any antidepressant during the relevant period of exposure. |
3rd trimester | 883 / -9 | This study assessed several SSRIs => data of all SSRI substances cannot be added (to keep adjustment). Thus, in order to avoid redundancy of control, only the substance with the higher number of exposure was used in the meta-analysis (i.e sertraline). | |
| Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis. | ||||||||
|
Martin - Sertraline 2024 |
Norway, Sweden and United Kingdom. 1996 - 2020 population based cohort retrospective |
The UK’s Clinical Practice Research Datalink (CPRD), the Norway’s Medical Birth Registry and the Sweden’s Medical Birth Register. | Singleton deliveries with maternal sertraline (without concurrent prescriptions for different antidepressants) use during pregnancy proxied by prescriptions in the United Kingdom and dispensations in Norway and Sweden. |
unexposed (general population or NOS)
Singleton deliveries without maternal antidepressants use during pregnancy proxied by prescriptions in the United Kingdom and dispensations in Norway and Sweden. |
during pregnancy (anytime or not specified) | 34604 / 2408707 | Overlapping: For SGA, Apgar and Preterm: Martin 2024 totally included Norby 2016 (2006-2012) and Skalkidou 2020 (2013-2017) for preterm only => Martin 2024 used because more pregnancies and adjustments. | |
| In the UK, prescription data were based on the prescriptions written by general practitioners (CPRD GOLD), whereas in Norway and Sweden, dispensation of prescription drugs from all ambulatory pharmacies was used (Norwegian Prescription Database, and Swedish Prescribed Drug Register). | ||||||||
|
Maschi - Fluoxetine 2008 |
Italy 1995 - 2003 prospective cohort |
A Drug and Health Information Centre in Milan, Italy. | Women who took Fluoxetine during pregnancy and delivered liveborn children. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who were counselled at the Centre on the use of nonteratogenic drugs or drugs that do not cause neonatal adverse effects, such as antibiotics or paracetamol. |
during pregnancy (anytime or not specified) | 32 / 192 | 'In all, 33 women (17%) had taken more than one antidepressant drug and 86 (43%) had received these medications in combination with a benzodiazepine.' Not the same women in the control group for paroxetine and fluoxetine. | |
| Maternal demographic data, indication for treatment and time of exposure were collected using a structured questionnaire. | ||||||||
|
Maschi - Paroxetine 2008 |
Italy 1995 - 2003 prospective cohort |
A Drug and Health Information Centre in Milan, Italy. | Women who took Paroxetine during pregnancy and delivered liveborn children. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who were counselled at the Centre on the use of nonteratogenic drugs or drugs that do not cause neonatal adverse effects, such as antibiotics or paracetamol. |
during pregnancy (anytime or not specified) | 58 / 348 | 'In all, 33 women (17%) had taken more than one antidepressant drug and 86 (43%) had received these medications in combination with a benzodiazepine.' Not the same women in the control group for paroxetine and fluoxetine. | |
| Maternal demographic data, indication for treatment and time of exposure were collected using a structured questionnaire. | ||||||||
|
Merlob 2009 |
Israel 2000 - 2007 prospective cohort |
The Departments of Neonatology in Rabin Medical Center and Schneider Children’s Medical Center of Israel (affiliated with ENTIS). | Pregnant women who reported using Selective serotonin reuptake inhibitors (SSRIs) during the first trimester. |
unexposed (general population or NOS)
Pregnant women who not reported using Selective serotonin reuptake inhibitors (SSRIs). |
1st trimester | 235 / 67636 | 'Any infant with multiple congenital anomalies or dysmorphic features underwent genetic evaluation by a trained expert to exclude a congenital syndrome.' | |
| A standardized pregnancy questionnaire is administered to all women on admittance to the maternity ward and reviewed by the attending neonatologist. The use of any drug during pregnancy is routinely recorded. | ||||||||
|
Misri 2006 |
Canada 1997 - 1999 prospective cohort |
The Reproductive Mental Health Program at British Columbia Women’s Hospital in Vancouver. | Children of depressed/anxious mothers exposed to selective serotonin reuptake inhibitor (SSRI) only during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Children of healthy, nondepressed, and nonmedicated mothers. |
during pregnancy (anytime or not specified) | 13 / 14 | Overlapping of some outcomes (Clinician ratings - the Crowell procedure) at 4-5 years old) with Oberlander 2007 which include a little more pregnancies, thus these outcomes not reported for Misri 2006. | |
| Recruitment for the subject/depressed groups was done during pregnancy, while recruitment for the control group began after delivery. | ||||||||
|
Morimoto 2021 |
Japan 2010 - 2019 retrospective cohort |
The Okayama University Hospital, Okayama, Japan. | Use of selective serotonin reuptake inhibitors (SSRIs) continued before or during pregnancy until just before delivery. |
exposed to other treatment, sick
No use of selective serotonin reuptake inhibitors (SSRIs) (but mothers exposed to antipsychotics, antidepressants, sedatives, or anticonvulsants). |
late pregnancy | 33 / 126 | ||
| Medication records were investigated to confirm the use of antipsychotics, selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, anticonvulsants, and nonbenzodiazepine hypnotics. | ||||||||
|
Mulder 2011 |
The Netherlands Not specified. prospective cohort |
A part of a larger prospective project on the impact of SSRI antidepressant medication use during pregnancy. | Fetuses exposed to Selective serotonin reuptake inhibitors (SSRIs) throughout pregnancy |
unexposed, disease free
Unexposed fetuses (no SSRI at study entry and during the remainder of their pregnancy) of healthy women with no history of psychiatric or other illnesses. |
at least 1st trimester, throughout pregnancy | 96 / 130 | The majority used paroxetine (44%), 21% used fluoxetine (type 2), 20% used citalopram (type 3), 7% used venlafaxine, 4% used fluvoxamine, and 4% took sertraline. | |
| A longitudinal design with three times of assessment aimed to collect data for the mother and her fetus at 15–19 wGA at time 1 (T1), 27–29 wGA at time 2 (T2), and 37–39 wGA at time 3 (T3). A questionnaire booklet was mailed to the participant about 1 week before each appointment. | ||||||||
|
Nielsen 2017 |
Denmark 1996 - 2016 population based cohort retrospective |
A population-based nationwide cohort study from Danish health registries. | All children of women who had filled one or more prescriptions of Selective serotonin reuptake inhibitors (SSRIs) from 30 days before conception to end of first trimester (end of 12th week of pregnancy).. |
unexposed (general population or NOS)
All children that mothers did not fill prescriptions of Selective serotonin reuptake inhibitors (SSRIs) from 30 days before conception to end of first trimester. |
1st trimester | 19807 / 1236510 | ||
| The Nationwide Prescription Database, for all reimbursed drug prescriptions issued from Danish pharmacies. | ||||||||
|
Nijenhuis (Controls exposed to TCA) 2012 |
The Netherlands 1995 - 2009 retrospective cohort (claims database) |
The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl | Children of mothers exposed to selective serotonin re-uptake inhibitors (SSRIs) during pregnancy. |
exposed to other treatment, sick
Children of mothers exposed to tricyclic antidepressants (TCAs) during pregnancy. |
1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy | 527 / 76 | The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. SSRI: Paroxetine (n = 310), fluoxetine (n = 105), citalopram (n = 60), fluvoxamine (n = 60), sertraline (n = 19), escitalopram (n = 2). | |
| The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands. | ||||||||
|
Nijenhuis (Controls unexposed, NOS) 2012 |
The Netherlands 1995 - 2009 retrospective cohort (claims database) |
The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl | Children of mothers exposed to selective serotonin re-uptake inhibitors (SSRIs) during pregnancy. |
unexposed (general population or NOS)
Children of mothers who did not use any selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) during pregnancy and during a period of 7 days before pregnancy. |
1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy | 527 / 34908 | The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. SSRI: Paroxetine (n = 310), fluoxetine (n = 105), citalopram (n = 60), fluvoxamine (n = 60), sertraline (n = 19), escitalopram (n = 2). | |
| The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands. | ||||||||
|
Nishigori 2017 |
Japan 2011 - 2014 population based cohort retrospective |
The Japan Environment and Children’s Study (JECS), an ongoing nationwide birth cohort study. | Any Selective serotonin reuptake inhibitors (SSRI) use, up to the 12th gestational week. |
unexposed (general population or NOS)
No Selective serotonin reuptake inhibitors (SSRI) use before and during pregnancy. |
1st trimester | 172 / 95433 | ||
| The researchers gathered information on drug use both before and after pregnancy using two interviews in the first gestational trimester then the 2nd or 3rd gestational trimester. For these two questionnaires, the research coordinators collected the information using direct interviews. | ||||||||
|
Norby 2016 |
Sweden 2006 - 2012 population based cohort retrospective |
The Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. | Infants of mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy (at any time during or 1 month before the pregnancy). |
unexposed (general population or NOS)
No antidepressant use during pregnancy. |
1st and 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified) | 17736 / 718533 | Overlapping: Malformations not reported because overlapping with Furu 2015: larger study (including Sweden). For preterm, SGA and Apgar: Martin 2024 used rather than Norby 2016 or Sujan 2017 (less expo/adjustments). | |
| At their initial visit, in 90% of the cases in the 1st trimester, the women are interviewed by their midwife, medication data are prospectively collected and registered in the Medical Birth Register (MBR). Data on medications were acquired from this way (MBR) and the PDR (Prescribed Drug Register). | ||||||||
|
Nordeng (Controls unexposed, NOS) 2012 |
Norway 2000 - 2006 cohort |
The Norwegian Mother and Child Cohort Study (the MoBa study). | Exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
No reported use of any antidepressants in the 6 months before or during pregnancy. |
1st trimester, during pregnancy (anytime or not specified) | 572 / 61648 | Little overlapping between Nordeng 2012 (2000 - 2006) and Furu 2015 (including Norway 2005-10) => the 2 studies kept. | |
| The pregnant women completed 2 questionnaires during pregnancy at around gestational weeks 17 and 30, which included notably questions regarding medication use. | ||||||||
|
Nordeng (Controls unexposed, sick) 2012 |
Norway 2000 - 2006 cohort |
The Norwegian Mother and Child Cohort Study (the MoBa study). | Exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnancies that reported use of an antidepressant during the 6 months before pregnancy, but not during pregnancy. |
1st trimester, during pregnancy (anytime or not specified) | 572 / 1048 | Little overlapping between Nordeng 2012 (2000 - 2006) and Furu 2015 (including Norway 2005-10) => the 2 studies kept. | |
| The pregnant women completed 2 questionnaires during pregnancy at around gestational weeks 17 and 30, which included notably questions regarding medication use. | ||||||||
|
Nulman (Controls unexposed, disease free) 2012 |
Canada 2001 - 2006 prospective cohort |
The Motherisk program at the Hospital for Sick Children in Toronto. | Depressed women who took selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, disease free
Nondepressed, healthy pregnant women who called Motherisk to inquire about nonteratogenic exposure (e.g., acetaminophen). |
during pregnancy (anytime or not specified) | 62 / 62 | 'Excluded were mothers exposed to polytherapy for depression or known teratogens, mothers with substance abuse, mothers with other psychiatric conditions, prematurity, mothers and/or children with medical conditions that may affect cognitive outcomes.' | |
| At the time of the first contact with Motherisk during pregnancy, information about medications was collected. | ||||||||
|
Nulman (Controls unexposed, sick) 2012 |
Canada 2001 - 2006 prospective cohort |
The Motherisk program at the Hospital for Sick Children in Toronto. | Depressed women who took selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed, sick
Depressed women who were untreated during pregnancy (discontinued pharmacotherapy before conception). |
during pregnancy (anytime or not specified) | 62 / 54 | 'Excluded were mothers exposed to polytherapy for depression or known teratogens, mothers with substance abuse, mothers with other psychiatric conditions, prematurity, mothers and/or children with medical conditions that may affect cognitive outcomes.' | |
| At the time of the first contact with Motherisk during pregnancy, information about medications was collected. | ||||||||
|
Nulman - Fluoxetine (Controls exposed to TCA) 1997 |
Canada Since 1985 prospective cohort |
The Motherisk Program, an information and consultation service regarding exposure to drugs, chemicals, radiation, and infectious agents during pregnancy and lactation. | Pregnant women who took fluoxetine at least during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women who took a tricyclic antidepressant drug at least during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
at least 1st trimester | 55 / 80 | Overlapping of some outcomes (language development) with Nulman 2002 (with more relevant period of exposure), thus not reported here. For Cognitive Index: the nb of infants examined by Bayley or McCarthy scales not provided. => data not extractable. | |
| During the initial assessment, at the diagnosis of pregnancy or within several weeks thereafter, the Service obtained a medical history of each woman, including use of medicinal drugs. Information concerning the time of drug therapy was recorded, as were the doses and of any concomitantly drugs. | ||||||||
|
Nulman - Fluoxetine (Controls exposed to TCA) 2002 |
Canada Until 1985 prospective cohort |
The Motherisk Program | Pregnant women diagnosed as having major depression who had been counseled by the program regarding therapy with fluoxetine and who had continued taking these medications throughout gestation. |
exposed to other treatment, sick
Pregnant women diagnosed as having major depression who had been counseled by the program regarding therapy with tricyclic antidepressants and who had continued taking these medications throughout gestation. |
throughout pregnancy | 40 / 46 | 'Eighteen mother-child pairs exposed to fluoxetine and 36 exposed to tricyclic antidepressants who were part of our original study (Nulman 1997) and who were exposed to these drugs throughout gestation were included in the present study.' | |
| During the initial consultation, during early pregnancy, Details concerning the time and duration of exposure to the antidepressant drugs, and the doses of any other concomitant medications were recorded was obtained from each mother. | ||||||||
|
Nulman - Fluoxetine (Controls unexposed, disease free) 2002 |
Canada Until 1985 prospective cohort |
The Motherisk Program | Pregnant women diagnosed as having major depression who had been counseled by the program regarding therapy with fluoxetine and who had continued taking these medications throughout gestation. |
unexposed, disease free
Pregnant women who had no history of a psychiatric disorder or depressive symptoms and were unexposed to any drug, chemical, radiation, or infection known to affect the fetus adversely. |
throughout pregnancy | 40 / 36 | 'Eighteen mother-child pairs exposed to fluoxetine and 36 exposed to tricyclic antidepressants who were part of our original study (Nulman 1997) and who were exposed to these drugs throughout gestation were included in the present study.' | |
| During the initial consultation, during early pregnancy, Details concerning the time and duration of exposure to the antidepressant drugs, and the doses of any other concomitant medications were recorded was obtained from each mother. | ||||||||
|
Nulman - Fluoxetine (Controls unexposed, NOS) 1997 |
Canada Since 1985 prospective cohort |
The Motherisk Program, an information and consultation service regarding exposure to drugs, chemicals, radiation, and infectious agents during pregnancy and lactation. | Pregnant women who took fluoxetine at least during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women not exposed to any drug, chemical, radiation, or infection known to affect the fetus adversely. |
at least 1st trimester | 55 / 84 | Overlapping of some outcomes (language development) with Nulman 2002 (with more relevant period of exposure), thus not reported here. For Cognitive Index: the nb of infants examined by Bayley or McCarthy scales not provided. => data not extractable. | |
| During the initial assessment, at the diagnosis of pregnancy or within several weeks thereafter, the Service obtained a medical history of each woman, including use of medicinal drugs. Information concerning the time of drug therapy was recorded, as were the doses and of any concomitantly drugs. | ||||||||
|
Oberlander 2004 |
Canada 1996 - 2000 prospective cohort |
The British Columbia Women's Hospital (Vancouver, British Columbia). | Infants prenatally exposed to Selective serotonin reuptake inhibitors (SSRIs) alone. |
unexposed, disease free
Term-born healthy infants whose mother did not use psychotropic or antidepressant medications during pregnancy and without history of maternal mental illness. |
during pregnancy (anytime or not specified) | 28 / 23 | Overlapping between Hutchison 2019a (not specified study period - 6 years old) and Oberlander 2004 (1996 - 2000 - 8 months old) => not assessable but probably low because each study is a small sample of the larger study. | |
| Measure of plasma level of maternal Selective serotonin reuptake inhibitor medications. | ||||||||
|
Oberlander 2007 |
Canada 1997 - 1999 prospective cohort |
The Reproductive Mental Health Program at British Columbia Women’s Hospital, Vancouver. | Children prenatally exposed to Selective Serotonin Reuptake Inhibitor (SSRIs). |
unexposed, disease free
Children of mothers without psychotropic, illicit drug use or antidepressant medication use during the pregnancy and without history of maternal mental illness. |
during pregnancy (anytime or not specified) | 22 / 14 | Overlapping of some outcomes (Mental and Psychomotor Development Index) with Oberlander 2004 which include a little more pregnancies, thus these outcomes not reported for Oberlander 2007 (which focuses on Externalizing disorders). | |
| Recruitment for the subject/depressed groups was done during pregnancy, while recruitment for the control group began after delivery (during the newborn period). | ||||||||
|
Oberlander a 2008 |
Canada 1997 - 2002 retrospective cohort (claims database) |
Population-based health-care utilization databases from the province of British Columbia. | Infants exposed to serotonin reuptake inhibitor (SRI) monotherapy in the first trimester of pregnancy. |
unexposed (general population or NOS)
Infants with no exposure to either of these drugs (SRI or benzodiazepine) in the first trimester of pregnancy. |
1st trimester | 2625 / 107320 | Serotonin reuptake inhibitor (SRI) includes SSRI and venlafaxine (7.1%). Because the rate of SSRI is above 90%, SRI are mainly represented by SSRI, and can be used as SSRI group. | |
| PharmaNet, a province-wide network recording all prescriptions dispensed by British Columbian pharmacists outside hospitals. | ||||||||
|
Olstad - (Es)citalopram (Controls unexposed, disease free) 2023 |
Norway 1998 - 2008 population based cohort propective |
The Norwegian Mother, Father and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health (NIPH). | Singleton births with prenatal (es)citalopram exposure, defined as reported use at any time during pregnancy. |
unexposed, disease free
Singleton births unexposed prenatally to antidepressants and maternal depression (self reported by mother). |
during pregnancy (anytime or not specified) | 306 / 344 | In the (es)citalopram group, other antidepressants were allowed, except when used concomitantly with (es)citalopram on the same indication. The indications for (es)citalopram were depression, anxiety, and other mental health problems. | |
| Information about the maternal use of (es)citalopram was retrieved from the questionnaires Q1, Q3, and Q4 for 4-week intervals (gestational weeks 0–4; 5–8; 9–12; 13–16; 17–20; 21–24; 25–28; 30–birth). | ||||||||
|
Olstad - (Es)citalopram (Controls unexposed, sick) 2023 |
Norway 1998 - 2008 population based cohort propective |
The Norwegian Mother, Father and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health (NIPH). | Singleton births with prenatal (es)citalopram exposure, defined as reported use at any time during pregnancy. |
unexposed, sick
Singleton births prenatally exposed to maternal depression (self reported by mother). |
during pregnancy (anytime or not specified) | 306 / 308 | In the (es)citalopram group, other antidepressants were allowed, except when used concomitantly with (es)citalopram on the same indication. The indications for (es)citalopram were depression, anxiety, and other mental health problems. | |
| Information about the maternal use of (es)citalopram was retrieved from the questionnaires Q1, Q3, and Q4 for 4-week intervals (gestational weeks 0–4; 5–8; 9–12; 13–16; 17–20; 21–24; 25–28; 30–birth). | ||||||||
|
Ozturk - Escitalopram 2016 |
Turkey 2007 - 2012 prospective cohort |
An observational cohort study based on a prenatal consultation service. | Pregnant women exposed to Escitalopram during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women selected from the non-teratogen exposed pregnancies in the same year. |
at least 1st trimester | 35 / 275 | This study assessed several SSRIs, with potential co-exposures => data of all SSRI substances cannot be added. To avoid redundancy of control, only the substance with the higher number of exposure was used in the meta-analysis (i.e escitalopram). | |
| At the first contact, initiated via gynecologists, a detailed patient history form was used to notably record all drug exposures (dose, duration and timing in pregnancy). | ||||||||
|
Palmsten 2020 |
USA 2012 - 2016 retrospective cohort (claims database) |
OptumLabs® Data Warehouse (OLDW), an administrative healthcare datasource of commercially insured enrollees with comprehensive insurance coverage for physician, hospital, and prescription drug services. | Pregnant women with dispensation of selective serotonin reuptake inhibitor antidepressants (SSRIs) monotherapy during different trajectories of exposure. (This is a subgroup of exposure among the whole exposed group considered in the study). Exposed group: addition of trajectories B, D and E. |
unexposed, sick
Pregnant women with a depression diagnosis (during the relevant exposure period) without antidepressant dispensings. |
1st and 2nd trimester, during pregnancy (anytime or not specified) | 3804 / 4949 | Exposed group: addition of trajectories B, D and E. Unexposed group: depression group was used (rather than anxiety group) to better reflect confounding by indication. | |
| Antidepressant pharmacy dispensing information from 3 months before the LMP through 35 gestational weeks. | ||||||||
|
Palmsten (control exposed to TCA) 2013 |
USA 2000 - 2007 retrospective cohort (claims database) |
The US nationwide Medicaid Analytic eXtract (MAX). | Pregnant women with a depression diagnosis and a dispensation of selective serotonin reuptake inhibitor (SSRI) in monotherapy during the exposure window. |
exposed to other treatment, sick
Pregnant women with a depression diagnosis and a dispensation of tricyclic antidepressant in monotherapy during the exposure window. |
2nd and/or 3rd trimester | 19000 / 441 | Women who received only one antidepressant class during the window were classified as having either SSRI, SNRI, tricyclic, bupropion or other antidepressant (mirtazapine, nefazodone, trazodone) monotherapy. | |
| Outpatient pharmacy-dispensing data. | ||||||||
|
Palmsten (Controls exposed to TCA) 2012 |
Canada 1997 - 2006 retrospective cohort (claims database) |
Population-based health-care utilization databases from the province of British Columbia. | Pregnant women with at least 1 pharmacy dispensing record for a selective serotonin reuptake inhibitor (SSRI) during estimated gestational weeks 10–20 (Monotherapy). |
exposed to other treatment, sick
Pregnant women with at least 1 pharmacy dispensing record for a tricyclic antidepressant during estimated gestational weeks 10–20 (Monotherapy). |
2nd trimester | 3169 / 146 | 'Exposure was classified as monotherapy if dispensings for only 1 antidepressant class were present during pregnancy and as polytherapy otherwise.' | |
| PharmaNet database, which contains all non-hospital pharmacy dispensings. | ||||||||
|
Palmsten (Controls unexposed, sick) 2013 |
USA 2000 - 2007 retrospective cohort (claims database) |
The US nationwide Medicaid Analytic eXtract (MAX). | Pregnant women with a depression diagnosis and a dispensation of selective serotonin reuptake inhibitor (SSRI) in monotherapy during the exposure window. |
unexposed, sick
Pregnant women with a depression diagnosis and no antidepressant exposure between the LMP and the end of the exposure window. |
2nd and/or 3rd trimester | 19000 / 59219 | Women who received only one antidepressant class during the window were classified as having either SSRI, SNRI, tricyclic, bupropion or other antidepressant (mirtazapine, nefazodone, trazodone) monotherapy. | |
| Outpatient pharmacy-dispensing data. | ||||||||
|
Palmsten (Controls unexposed, sick) 2012 |
Canada 1997 - 2006 retrospective cohort (claims database) |
Population-based health-care utilization databases from the province of British Columbia. | Pregnant women with at least 1 pharmacy dispensing record for a selective serotonin reuptake inhibitor (SSRI) during estimated gestational weeks 10–20 (Monotherapy). |
unexposed, sick
Pregnant women with no antidepressant dispensings between the year prior to the last menstrual period and gestational week 20. |
2nd trimester | 3169 / 65392 | 'Exposure was classified as monotherapy if dispensings for only 1 antidepressant class were present during pregnancy and as polytherapy otherwise.' | |
| PharmaNet database, which contains all non-hospital pharmacy dispensings. | ||||||||
|
Palmsten b 2013 |
USA 2000 - 2007 retrospective cohort (claims database) |
The Medicaid Analytic eXtract (MAX) data | Women with a supply of Selective serotonin reuptake inhibitor (SSRIs) monotherapy that overlapped with the delivery date. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Women who had no supply of antidepressants in the five months before delivery. |
late pregnancy | 11516 / 69044 | Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery. | |
| Data of prescription. | ||||||||
|
Pastuszak - Fluoxetine (Controls exposed to TCA) 1993 |
USA and Canada Not specified prospective cohort |
Four Teratogen Information Services (TIS): Motherisk (Toronto, Ontario), Pregnancy Healthline (Philadelphia, Pa), Pregnancy Risk Information Service (Camden,NJ) and Pregnancy Risk Line (Salt Lake City, Utah). | Pregnant women exposed to fluoxetine during the first trimester. |
exposed to other treatment, sick
Pregnant women exposed to tricyclic antidepressants (TCAs) during the first trimester. |
1st trimester | 74 / 74 | The matched cohort was considered. Authors made comparison Fluoxetine versus TCAs, thus considered as mono-exposure. | |
| Drug exposure history was obtained from both the mother and biological father of the fetus, by an interview with a team physician. | ||||||||
|
Pastuszak - Fluoxetine (Controls unexposed, NOS) 1993 |
USA and Canada Not specified prospective cohort |
Four Teratogen Information Services (TIS): Motherisk (Toronto, Ontario), Pregnancy Healthline (Philadelphia, Pa), Pregnancy Risk Information Service (Camden,NJ) and Pregnancy Risk Line (Salt Lake City, Utah). | Pregnant women exposed to fluoxetine during the first trimester. |
unexposed (general population or NOS)
Pregnant women who sought counseling at Motherisk regarding exposure to a nonteratogen. |
1st trimester | 128 / 128 | Authors made comparison Fluoxetine versus TCAs, thus considered as mono-exposure. | |
| Drug exposure history was obtained from both the mother and biological father of the fetus, by an interview with a team physician. | ||||||||
|
Pearson (Controls exposed to TCA) 2007 |
USA 1996 - 2000 retrospective cohort |
The Perinatal and Reproductive Psychiatry Program at the Massachusetts General Hospital. | Infants whose mothers with primary major affective or anxiety disorders used serotonin reuptake inhibitor (SRIs) during any portion of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants whose mothers with primary major affective or anxiety disorders used Tricyclic antidepressants (TCAs) during any portion of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
during pregnancy (anytime or not specified) | 42 / 37 | SRI: fluoxetine (N = 17), sertraline (N = 13), paroxetine (N = 12). TCA: nortriptyline (N = 13), imipramine (N = 11), desipramine (N = 7), clomipramine (N = 4), amitriptyline (N = 2). | |
| Review of obstetrical and neonatal records. | ||||||||
|
Pearson (Controls unexposed, NOS) 2007 |
USA 1996 - 2000 retrospective cohort |
The Perinatal and Reproductive Psychiatry Program at the Massachusetts General Hospital. | Infants whose mothers with primary major affective or anxiety disorders used serotonin reuptake inhibitor (SRIs) during any portion of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Infants whose mothers were not exposed to an antidepressant drug during pregnancy. |
during pregnancy (anytime or not specified) | 42 / 168 | SRI: fluoxetine (N = 17), sertraline (N = 13), paroxetine (N = 12). | |
| Review of obstetrical and neonatal records. | ||||||||
|
Pedersen 2010 |
Denmark 1996 - 2002 population based cohort retrospective |
The Danish National Birth Cohort, a nationwide, ongoing, follow-up study of pregnant women and their offspring. | Live-born singletons of pregnant women that reported use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Live-born singletons of pregnant women depressed during pregnancy but did not report use of any psychotropic medication (untreated depression). |
1st trimester, 2nd and/or 3rd trimester, during pregnancy (anytime or not specified) | -9 / 479 | Among the 415 women treated with antidepressants, 336 used 1 type of SSRI only, 12 used >1 SSRI, 28 used only TCAs, and 29 used other types of antidepressants only (eg, venlafaxine). Ten used combinations of SSRIs, TCAs, and other antidepressants. | |
| Information on medication use in early pregnancy was obtained partly through a self- administered questionnaire linked to the consent form. After consent was obtained, the women were contacted twice during pregnancy. | ||||||||
|
Rai (Controls exposed to TCA) 2017 |
Sweden 2001 - 2011 prospective cohort |
The Stockholm youth cohort, an observational prospective cohort study of Stockholm County. | Children of mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of mothers who used Clomipramine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
during pregnancy (anytime or not specified) | 2710 / 235 | Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy. | |
| Information on maternal use of antidepressants in pregnancy is derived from the medical birth register (as reported by pregnant women at their antenatal interview, at a median of 10 weeks’ gestation) and supplemented it with the prescribed drug register (available from July 2005). | ||||||||
|
Rai (Controls unexposed, disease free) 2017 |
Sweden 2001 - 2011 prospective cohort |
The Stockholm youth cohort, an observational prospective cohort study of Stockholm County. | Children of mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
No maternal psychiatric disorder and unexposed to antidepressants |
during pregnancy (anytime or not specified) | 2710 / 238943 | Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy. | |
| Information on maternal use of antidepressants in pregnancy is derived from the medical birth register (as reported by pregnant women at their antenatal interview, at a median of 10 weeks’ gestation) and supplemented it with the prescribed drug register (available from July 2005). | ||||||||
|
Rai (Controls unexposed, sick) 2017 |
Sweden 2001 - 2011 prospective cohort |
The Stockholm youth cohort, an observational prospective cohort study of Stockholm County. | Children of mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children of mothers with psychiatric disorders (any time before the birth of the child) who did not take antidepressants during pregnancy. |
during pregnancy (anytime or not specified) | 2710 / 12325 | Overlapping: Rai 2017 is an update of Rai 2013. About 3% with co-exposure to SSRI and Non-SSRI antidepressants (91/3342) => considered as SSRI monotherapy and Non-SSRI monotherapy. | |
| Information on maternal use of antidepressants in pregnancy is derived from the medical birth register (as reported by pregnant women at their antenatal interview, at a median of 10 weeks’ gestation) and supplemented it with the prescribed drug register (available from July 2005). | ||||||||
|
Rampono 2009 |
Australia Not specified. prospective cohort |
The outpatient clinics of the Department of Psychological Medicine at King Edward Memorial Hospital, Western Australia. | Pregnant patients treated with Selective serotonin reuptake inhibitor (SSRI) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women untreated with antidepressants during pregnancy. |
during pregnancy (anytime or not specified) | 27 / 18 | Maternal antenatal EPDS scores were not different between cases and controls. Mothers who were known substance abusers, or who took any medication known to alter infant behaviour (apart from those being investigated) were excluded from the study. | |
| The antidepressant and dose for each individual patient was determined by the prescriber (JR) according to the patients needs. The analyses of medicines and metabolites in maternal and infant plasma were carried out by high performance liquid chromatography. | ||||||||
|
Raviv 2025 |
Israel 2011 - 2022 retrospective cohort |
Lis Maternity and Women’s Hospital, Tel Aviv Sourasky Medical Center (TASMC), Israel and the Israeli National Newborn Screen (NBS) Program. | Infants born at term with gestational Selective serotonin reuptake inhibitors (SSRI) treatment. |
unexposed (general population or NOS)
Infants born at term from the general population. |
during pregnancy (anytime or not specified) | 2321 / 103607 | ||
| The mother’s information retrieved from the maternity hospital database included the reported Selective serotonin reuptake inhibitor treatment during the current pregnancy. | ||||||||
|
Reebye 2002 |
Canada 1997 - 1999 prospective cohort |
The Department of Reproductive Psychiatry, Children’s and Women’s Health Centre of British Columbia, Canada | Depressed mothers receiving Selective serotonin reuptake inhibitors (SSRI) alone during pregnancy. |
unexposed, disease free
Nondepressed (clinically and by self-report), nontreated (psychotropic medications) healthy (no other serious comorbid pathology) mothers and their healthy infants (living with biological mothers). |
during pregnancy (anytime or not specified) | 24 / 23 | Overlapping: Some outcomes (Mental and Psychomotor Development Index) also reported by Oberlander 2004 which include a little more pregnancies, thus these outcomes not reported for Reebye 2002. | |
| Recruitment for the subject/depressed groups was done during pregnancy, while recruitment for the control group began on day 1 postpartum. | ||||||||
|
Reis (Controls exposed to TCA) 2010 |
Sweden 1995 - 2007 population based cohort retrospective |
The Swedish Medical Birth Register (MBR), Register of Birth Defects and the Patient Register (previous the Hospital Discharge Register). | Pregnant women who reported the use of selective serotonin receptor inhibitors (SSRIs) in early or late pregnancy or were prescribed SSRIs during pregnancy. |
exposed to other treatment, sick
Pregnant women who reported the use of tricyclic antidepressants (TCAs) in early or late pregnancy or were prescribed TCAs during pregnancy. |
2nd and/or 3rd trimester, early pregnancy | 10170 / 1662 | For preterm and SGA: overlapping Reis 2010 (95-07); Norby (06-12) and Sujan 2017 (96-12): Reis and Norby (more exposures). | |
| Information on drug use is partly based on an interview conducted by the midwife at the first antenatal visit (in 90% of cases before the end of the first trimester) and partly on information from the antenatal care with respect to drugs prescribed later during the pregnancy by the attending doctor. | ||||||||
|
Reis (Controls unexposed, NOS) 2010 |
Sweden 1995 - 2007 population based cohort retrospective |
The Swedish Medical Birth Register (MBR), Register of Birth Defects and the Patient Register (previous the Hospital Discharge Register). | Pregnant women who reported the use of selective serotonin receptor inhibitors (SSRIs) in early or late pregnancy or were prescribed SSRIs during pregnancy. |
unexposed (general population or NOS)
All other pregnant women in the register (not exposed to antidepressants during pregnancy). |
2nd and/or 3rd trimester, early pregnancy | 10170 / 1062190 | For preterm and SGA: overlapping Reis 2010 (95-07); Norby (06-12) and Sujan 2017 (96-12): Reis and Norby (more exposures). | |
| Information on drug use is partly based on an interview conducted by the midwife at the first antenatal visit (in 90% of cases before the end of the first trimester) and partly on information from the antenatal care with respect to drugs prescribed later during the pregnancy by the attending doctor. | ||||||||
|
Richardson 2019 |
United Kingdom 1995 - 2018 prospective cohort |
The UK Teratology Information Service (UKTIS), a prospective observational comparative cohort study. | Pregnancies in which mothers had used Selective Serotonin Reuptake Inhibitor (SSRI) at any stage of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnancies unexposed to any antidepressant medications (exposure to agents not known to be teratogenic). |
1st trimester, during pregnancy (anytime or not specified) | 843 / 1405 | 'Exposure to known or suspected human teratogens/fetotoxic agents were excluded'. Overlapping: this study included data published by Martin 2018 (abstract). | |
| Upon contact with the service, information (including medication use) is collected from the health professional to allow accurate fetal risk assessment. | ||||||||
|
Robinson-Wolrath 2016 |
Australia 2005 - 2010 retrospective cohort |
The King Edward Memorial Hospital, Perth, Australia. | Mothers treated with Selective serotonin inhibitors (SSRIs) during pregnancy. |
unexposed (general population or NOS)
Mothers not treated with Selective serotonin inhibitors (SSRIs) nor Serotonin noradrenaline reuptake inhibitors (SNRIs) during pregnancy. |
during pregnancy (anytime or not specified) | 295 / -9 | Number of unexposed pregnancies not specified (thus all data without OR provided by authors cannot be reported here). 75 babies of mothers prescribed multiple psychiatric medications excluded. | |
| Retrospective review of all pregnancies at King Edward Memorial Hospital, using midwifery and neonatal databases and case records. | ||||||||
|
Roca 2011 |
Spain 2004 - 2008 prospective cohort |
The Perinatal Psychiatry Program in a general teaching hospital. | Pregnant women with depressive or anxiety disorder who are treated with selective serotonin reuptake inhibitors (SSRIs) during regancy. |
unexposed, disease free
Pregnant women without an active psychiatric disorder during pregnancy who were non- exposed to antidepressants during pregnancy. |
during pregnancy (anytime or not specified) | 84 / 168 | ||
| Cases were followed throughout pregnancy by a clinical researcher, who recorded the type and dosage of antidepressants at each visit. | ||||||||
|
Rommel 2022 |
Denmark 1997 - 2015 population based cohort retrospective |
The Danish National Medical Birth Registry, the Danish National Patient Registry and the Danish National Prescription Registry. | Children whose mothers used selective serotonin reuptake inhibitors (SSRIs) monotherapy during pregnancy, i.e at least one prescription dispensed on any date from one month before pregnancy until delivery. |
unexposed, sick
Children whose mothers discontinued antidepressant before pregnancy (antidepressant use before but not during pregnancy). |
during pregnancy (anytime or not specified) | 16429 / 23676 | Overlapping: large overlapping for PPHN (with Kieler 2012) and malformations (with Furu 2015) => outcomes not reported here because other studies included higher number of pregnancies and 1st trimester exposure for malformations. | |
| Information on antidepressant use during pregnancy was retrieved from the Danish National Prescription Registry. | ||||||||
|
Sahingöz (Controls unexposed, disease free) 2014 |
Turkey Not specified retrospective cohort |
The Meram Faculty of Medicine of Necmettin Erbakan University, the Faculty of Medicine of Selcuk University in Konya, Turkey, and the Clinic of Bakırkoy Research and Training Hospital in Istanbul, Turkey | Consecutive women who were treated with selective serotonin reuptake inhibitors (SSRIs) for major depression during their current pregnancy. |
unexposed, disease free
Consecutive healthy women without any psychiatric disorder during their last pregnancy attending the outpatient clinic of neonatalogy for routine controls of their baby. |
during pregnancy (anytime or not specified) | 23 / 30 | ||
| Identification of exposure when pregnant women were admitted to the psychiatry outpatient clinics (from the 36th gestational week to 8 weeks postpartum). | ||||||||
|
Sahingöz (Controls unexposed, sick) 2014 |
Turkey Not specified retrospective cohort |
The Meram Faculty of Medicine of Necmettin Erbakan University, the Faculty of Medicine of Selcuk University in Konya, Turkey, and the Clinic of Bakırkoy Research and Training Hospital in Istanbul, Turkey | Consecutive women who were treated with selective serotonin reuptake inhibitors (SSRIs) for major depression during their current pregnancy. |
unexposed, sick
Consecutive untreated women with major depression who attended outpatient clinics because of depressive symptoms during their current postnatal period. |
during pregnancy (anytime or not specified) | 23 / 36 | ||
| Identification of exposure when pregnant women were admitted to the psychiatry outpatient clinics. | ||||||||
|
Salisbury (Controls unexposed, disease free) 2016 |
USA Not specified. prospective cohort |
A prospective, naturalistic cohort study from Women and Infants’ Hospital, Providence; Alpert Medical School of Brown University, Providence; the Butler Hospital, Providence; University of Maryland, College Park; ... | Infants of women who use Selective serotonin reuptake inhibitors (SSRI) for at least 4 weeks at any time during pregnancy among women with a current or lifetime diagnosis of a unipolar mood disorder. |
unexposed, disease free
Infants of women who did not meet criteria for any psychiatric disorder or report use of psychotropic medications during their entire pregnancy. |
during pregnancy (anytime or not specified) | 52 / 66 | The SRI exposed group (n=52) is composed of SSRI (n=47) and SNRI (n=5; 9.6%). SNRI is less than 10% of the exposed group, thus it is considered as SSRI group. | |
| Maternal self-report assessments during pregnancy. Cord blood samples were obtained at delivery for determination of plasma drug levels to confirm SSRI exposure. | ||||||||
|
Salisbury (Controls unexposed, sick) 2016 |
USA Not specified. prospective cohort |
A prospective, naturalistic cohort study from Women and Infants’ Hospital, Providence; Alpert Medical School of Brown University, Providence; the Butler Hospital, Providence; University of Maryland, College Park; ... | Infants of women who use Selective serotonin reuptake inhibitors (SSRI) for at least 4 weeks at any time during pregnancy among women with a current or lifetime diagnosis of a unipolar mood disorder. |
unexposed, sick
Infants of women pharmacologically untreated maternal depression. |
during pregnancy (anytime or not specified) | 52 / 56 | The SRI exposed group (n=52) is composed of SSRI (n=47) and SNRI (n=5; 9.6%). SNRI is less than 10% of the exposed group, thus it is considered as SSRI group. | |
| Maternal self-report assessments during pregnancy. Cord blood samples were obtained at delivery for determination of plasma drug levels to confirm SSRI exposure. | ||||||||
|
Scannell 2020 |
USA 2007 - 2017 retrospective cohort |
The Resident Diabetes in Pregnancy Clinic, USA (no other details). | Pregnant women with depression and diabetes who received medication therapy with Selective serotonin reuptake inhibitors (SSRIs). |
unexposed, sick
Pregnant women with depression and diabetes who did not receive medication therapy with Selective serotonin reuptake inhibitors (SSRIs). |
during pregnancy (anytime or not specified) | 149 / -9 | The number of pregnancies in control group not clearly provided (maybe 69 (27 %) who had no treatment or 106 who had no SSRIs). | |
| Not specified. | ||||||||
|
Simon (Controls exposed to TCA) 2002 |
USA 1986 - 1998 retrospective cohort (claims database) |
The Group Health Cooperative, a prepaid health plan serving approximately 400,000 members in Washington State. | Mothers with any selective serotonin reuptake inhibitor (SSRI) prescriptions during the 270 days before delivery. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Mothers with any tricyclic antidepressants prescriptions during the 270 days before delivery. (This is a subgroup of exposure among the whole exposed group considered in the study). |
during pregnancy (anytime or not specified) | 185 / 209 | Mainly monoexposure of class: 'infants exposed to more than one antidepressant: 5 in the SSRI group (co-expo of SSRI), none in the tricyclic antidepressant group'. | |
| Pharmacy records were used to identify all antidepressant prescriptions filled or refilled during the 360 days before delivery. | ||||||||
|
Simon (Controls unexposed, NOS) 2002 |
USA 1986 - 1998 retrospective cohort (claims database) |
The Group Health Cooperative, a prepaid health plan serving approximately 400,000 members in Washington State. | Mothers with any selective serotonin reuptake inhibitor (SSRI) prescriptions during the 270 days before delivery. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Mothers with no antidepressant prescriptions during the 360 days before delivery. |
during pregnancy (anytime or not specified) | 185 / 185 | Mainly monoexposure of class: 'infants exposed to more than one antidepressant: 5 in the SSRI group (co-expo of SSRI), none in the tricyclic antidepressant group'. | |
| Pharmacy records were used to identify all antidepressant prescriptions filled or refilled during the 360 days before delivery. | ||||||||
|
Sivojelezova - Citalopram 2005 |
Canada 1999 - 2002 prospective cohort |
The Motherisk Program, a teratogen information and counseling center. | Women who took citalopram during pregnancy. |
unexposed (general population or NOS)
Pregnant women women with nonteratogenic exposures (eg, acetaminophen, hair dyes, vitamins, etc). |
1st trimester, 3rd trimester, during pregnancy (anytime or not specified) | 132 / 132 | The disease-matched group treated with other SSRI antidepressants (eg, fluoxetine, paroxetine, sertraline) not reported here, because it also concerns exposure to SSRI. | |
| During an initial interview with a patient, a standardized intake form was completed over the telephone with information regard- ing general medical and obstetrical history, timing of drug exposure, and its dose schedule. | ||||||||
|
Sjaarda 2020 |
USA 2007 – 2011 prospective cohort |
A prospective cohort study of women trying to conceive and participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) clinical trial. | Women who became pregnant with exposure to selective serotonin reuptake inhibitors (SSRI) detected in urine samples during pregnancy. |
unexposed (general population or NOS)
Women who became pregnant without any antidepressant exposure at the same time point. |
early pregnancy, preconception-only | 75 / 662 | 'Women with SSRI use in this cohort may be considered to represent women with mild to moderate depression self-identified'. Results used were data for exposure at 'Week 4 of pregnancy' because available for all substances. | |
| Antidepressant medication exposure was measured in stored urine samples collected at study visits at enrollment and at the end of preconception follow-up. For women who became pregnant, samples from pregnancy visits at gestational weeks 4 and 8 were also evaluated. | ||||||||
|
Skalkidou (Controls unexposed, disease free) 2020 |
Sweden 2013 - 2017 population based cohort retrospective |
National register-based cohort study based on data from the Swedish Pregnancy Register. | Pregnant women with self-reported selective serotonin reuptake inhibitor (SSRI) use at any time point during pregnancy. |
unexposed, disease free
Healthy pregnant women with no psychiatric illness or reporting selective serotonin reuptake inhibitor (SSRI) use. |
during pregnancy (anytime or not specified) | 8643 / 268006 | Overlapping: for preterm: Skalkidou (2013 - 2017) included in Martin 2024 (2006-2020) => use of Martin 2024 because more exposed pregnancies and adjustments. | |
| Information on self-reported use of SSRI medication during pregnancy was collected at any of the 12 scheduled antenatal visits before delivery and entered by the caregiver in the maternal healthcare records. | ||||||||
|
Skalkidou (Controls unexposed, sick) 2020 |
Sweden 2013 - 2017 population based cohort retrospective |
National register-based cohort study based on data from the Swedish Pregnancy Register. | Pregnant women with self-reported selective serotonin reuptake inhibitor (SSRI) use at any time point during pregnancy. |
unexposed, sick
Pregnant women with self-reported prior or current psychiatric illness but non-selective serotonin reuptake inhibitor (SSRI) treated during pregnancy. |
during pregnancy (anytime or not specified) | 8643 / 28672 | Overlapping: for preterm: Skalkidou (2013 - 2017) included in Martin 2024 (2006-2020) => use of Martin 2024 because more exposed pregnancies and adjustments. | |
| Information on self-reported use of SSRI medication during pregnancy was collected at any of the 12 scheduled antenatal visits before delivery and entered by the caregiver in the maternal healthcare records. | ||||||||
|
Skurtveit 2014 |
Norway 1999 - 2008 prospective cohort |
A large prospective population-based pregnancy cohort, the Norwegian Mother and Child Cohort Study (MoBa). | Pregnant women that had reported use of any Selective serotonin reuptake inhibitors (SSRIs) at any time on the 17–18-week questionnaire (pregnancy week 0–18), or the 30-week questionnaire (week 19–29) or the 6-month questionnaire (week 30 until birth). |
unexposed (general population or NOS)
Pregnant women that had not reported use of any Selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
during pregnancy (anytime or not specified) | 386 / 51362 | Authors provided 2 durations of exposure (without results for any duration) => use of the maximal duration, i.e Use in at least two time periods. | |
| Maternal self-reported drug use obtained prospectively several times during pregnancy. The validity of data was explored with the prescription data from the Norwegian Prescription Database (NorPD). A redeemed prescription of SSRI was found in NorPD for 93% of the women who reported such use in MoBa. | ||||||||
|
Smith 2013 |
USA 2004 - 2008 prospective cohort |
The Yale Pink and Blue Study, a longitudinal cohort study, in Connecticut and Western Massachusetts, USA. | At term infant of mother who was not depressed in pregnancy yet was taking a serotonin reuptake inhibitor (only SSRI exposure) in the 3rd trimester. |
unexposed, disease free
At term infant of mother who was neither depressed nor taking antidepressant medications at any time in pregnancy. |
3rd trimester | 6 / 61 | Exposure to SRI included fluoxetine at a maximum of 20 mg/day, citalopram at an average dose of 20 mg/day, and sertraline at a maximum dose of 100 mg/day. | |
| A structured screening questionnaire collected information about pregnancy dates and antidepressant treatment was administrated during pregnancy. | ||||||||
|
Stephansson 2013 |
Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) 1996 - 2007 population based cohort retrospective |
A registry-based cohort study based on national registries of the 5 Nordic countries. | One or more filled prescriptions for an Selective serotonin reuptake inhibitors (SSRIs) from 3 months before the start of pregnancy until birth (different analysis according to period of exposure). |
unexposed (general population or NOS)
No prescriptions for an Selective serotonin reuptake inhibitors (SSRIs). |
1st and 2nd trimester, 3 months (or more) before pregnancy or during pregnancy, at least 1st trimester, throughout pregnancy | 29228 / 1604649 | Exclusion of pregnancies who had used other antidepressants with a serotonin or norepinephrine activity (but not other antidepressants). Overlapping: Jimenez-Solem 2013 (Stephansson 2013 used for common outcomes). No overlapping with Lennestal 2007 | |
| The prescription registries in the Nordic countries include data on the dispensed item, substance, brand name, and formulation together with date of dispensing for more than 95% of the total outpatient population. | ||||||||
|
Suarez (Controls unexposed, discontinuers) 2022 |
USA 2000 - 2015 retrospective cohort (claims database) |
The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), USA. | Individuals with at least 1 dispensing of selective serotonin reuptake inhibitors (SSRIs) from 127 days after LMP (week 19 of gestation) to delivery. |
unexposed, sick
Individuals that having a dispensing for selective serotonin reuptake inhibitors (SSRIs) in the window from 90 to 31 days prior to LMP but not during the window of 30 days prior to LMP through delivery. |
2nd and/or 3rd trimester | 115060 / 38038 | The Medicaid Analytic eXtract (MAX): 2000 to 2014 and the MarketScan Commercial Claims Database (MarketScan): 2003 to 2015. | |
| The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications. | ||||||||
|
Suarez (Controls unexposed, general pop) 2022 |
USA 2000 - 2015 retrospective cohort (claims database) |
The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), USA. | Individuals with at least 1 dispensing of selective serotonin reuptake inhibitors (SSRIs) from 127 days after LMP (week 19 of gestation) to delivery. |
unexposed (general population or NOS)
Individuals with no antidepressant dispensing from 90 days prior to pregnancy start through the day prior to delivery. |
2nd and/or 3rd trimester | 115110 / 3000907 | The Medicaid Analytic eXtract (MAX): 2000 to 2014 and the MarketScan Commercial Claims Database (MarketScan): 2003 to 2015. | |
| The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications. | ||||||||
|
Sujan (Controls unexposed, NOS) 2017 |
Sweden 1996 - 2012 population based cohort retrospective |
Linkage of Swedish registries. | Singleton offspring whose mother had first-trimester exposure to any selective serotonin reuptake inhibitors (SSRIs). (This is a subgroup of exposure among the whole exposed group considered). |
unexposed (general population or NOS)
Unexposed singleton offspring. |
1st trimester | 18470 / 1562159 | Use of data based on Maternal self-reported questionnaire. For preterm and SGA: overlapping between Reis 2010 (1995-2007); Norby (2006-2012) and Sujan 2017 (1996-2012): use of Reis and Norby because more exposures and more relevant period of exposure. | |
| Exposure was defined according to 2 sources of information: maternal self-reports (available from the Medical Birth Register for offspring born between 1996 and 2012) and dispensation records (from the Prescribed Drug Register; available for both parents of offspring born between 2006 and 2012). | ||||||||
|
Sujan (Controls unexposed, sibling) 2017 |
Sweden 1996 - 2012 population based cohort retrospective |
Linkage of Swedish registries. | Singleton offspring whose mother had first-trimester exposure to any selective serotonin reuptake inhibitors (SSRIs). (This is a subgroup of exposure among the whole exposed group considered). |
sibling
Siblings born to the same mothers discordant in view of exposure: no exposure to selective serotonin reuptake inhibitors (SSRIs). |
1st trimester | 9063 / 15906 | Preterm, SGA: Overlapping: Norby and Reis used rather than Sujan 2017 (less exposures). First-trimester exposure: at least 1 dispensation between 90 days before and 90 days after conception: Sensitivity analysis restricted to 30 days => considered as T1. | |
| Exposure was defined by maternal self-reports (available from the Medical Birth Register for offspring born between 1996 and 2012). | ||||||||
|
Suri 2007 |
USA 2000 - 2005 prospective cohort |
The University of California at Los Angeles (UCLA) Semel Institute for Neuroscience and Human Behavior. | Pregnant women with major depressive disorder who took antidepressant medication (> 90% selective serotonin reuptake inhibitors (SSRIs)) for more than 50% of their pregnancy |
unexposed, disease free
Healthy pregnant women with no psychiatric history. |
during pregnancy (anytime or not specified) | 49 / 19 | In the group exposed to antidepressants, more than 90% were exposed to selective serotonin reuptake inhibitors (SSRIs), there this group is considered as exposed to SSRIs. | |
| Participants underwent assessments on a monthly basis throughout their pregnancy. Participants were also seen by the study physician for a clinical assessment, which included collection of information about medications taken and medication dosages. | ||||||||
|
Suri - Fluoxetine (Controls unexposed, disease free) 2004 |
USA 1997 - 2000 prospective cohort |
Data from the University of California at Los Angeles Neuropsychiatric Institute. | Pregnant women with depression treated with fluoxetine at any time during pregnancy (medicated depressed group). |
unexposed, disease free
Pregnant women without depression and no antidepressant treatment during pregnancy. |
during pregnancy (anytime or not specified) | 28 / 16 | 'Exclusion criteria included the presence of psychotic symptoms, the use of medications that are known to adversely affect the fetus, the use of other psychotropic medications, the use of alcohol, cigarettes, or substances while pregnant'. | |
| Subjects recruited in the first trimester of pregnancy and that were then followed once in each trimester (NOS). | ||||||||
|
Suri - Fluoxetine (Controls unexposed, sick) 2004 |
USA 1997 - 2000 prospective cohort |
Data from the University of California at Los Angeles Neuropsychiatric Institute. | Pregnant women with depression treated with fluoxetine at any time during pregnancy (medicated depressed group). |
unexposed, sick
Pregnant women with depression and no antidepressant treatment during pregnancy (unmedicated depressed group). |
during pregnancy (anytime or not specified) | 28 / 18 | 'Exclusion criteria included the presence of psychotic symptoms, the use of medications that are known to adversely affect the fetus, the use of other psychotropic medications, the use of alcohol, cigarettes, or substances while pregnant'. | |
| Subjects recruited in the first trimester of pregnancy and that were then followed once in each trimester (NOS). | ||||||||
|
Sørensen (Controls exposed to TCA) 2013 |
Denmark 1996 - 2006 population based cohort retrospective |
The Danish Civil Registration System (CRS), the Danish National Prescription Registry (DNPR) and the Danish Psychiatric Central Register (DPCR). | Children of women who filled a prescription for Selective serotonin reuptake inhibitor (SSRI) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of women who filled a prescription for Tricyclic antidepressants (TCA) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
during pregnancy (anytime or not specified) | 7506 / 642 | For ASD: overlapping between Gidaya 2014, Hviid 2013; Sorensen 2013 and Liu 2017 (same dataset and period) => Liu was reported because larger study with an unexposed sick comparator. Low co-exposure SSRI/SNRI/TCA (<5%) => considered as monotherapies. | |
| The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist. | ||||||||
|
Sørensen (Controls unexposed, NOS) 2013 |
Denmark 1996 - 2006 population based cohort retrospective |
The Danish Civil Registration System (CRS), the Danish National Prescription Registry (DNPR) and the Danish Psychiatric Central Register (DPCR). | Children of women who filled a prescription for Selective serotonin reuptake inhibitor (SSRI) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children of women who not filled antidepressant drugs during pregnancy. |
1st trimester, 2nd and/or 3rd trimester, during pregnancy (anytime or not specified) | 7506 / 646782 | For ASD: overlapping between Gidaya 2014, Hviid 2013; Sorensen 2013 and Liu 2017 (same dataset and period) => Liu was reported because larger study with an unexposed sick comparator. Low co-exposure SSRI/SNRI/TCA (<5%) => considered as monotherapies. | |
| The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist. | ||||||||
|
Sørensen (Controls unexposed, sibling) 2013 |
Denmark 1996 - 2006 population based cohort retrospective |
The Danish Civil Registration System (CRS), the Danish National Prescription Registry (DNPR) and the Danish Psychiatric Central Register (DPCR). | Siblings children born to mothers who filled selective serotonin reuptake inhibitor (SSRI) from 30 days before conception to the day of birth. |
sibling
Siblings children born to mothers who not filled selective serotonin reuptake inhibitor (SSRI) drugs during pregnancy. |
during pregnancy (anytime or not specified) | 81 / 6036 | For ASD: overlapping between Gidaya 2014, Hviid 2013; Sorensen 2013 and Liu 2017 (same dataset and period) => Liu was reported because larger study with an unexposed sick comparator. Low co-exposure SSRI/SNRI/TCA (<5%) => considered as monotherapies. | |
| The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist. | ||||||||
|
Sørensen (Controls unexposed, sick) 2013 |
Denmark 1996 - 2006 population based cohort retrospective |
The Danish Civil Registration System (CRS), the Danish National Prescription Registry (DNPR) and the Danish Psychiatric Central Register (DPCR). | Children born to mothers with a hospital-diagnosed affective disorder who filled a prescription for selective serotonin reuptake inhibitor (SSRI) from 30 days before conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children born to mothers with a hospital-diagnosed affective disorder who not filled antidepressant drugs during pregnancy. |
during pregnancy (anytime or not specified) | 1475 / 4324 | For ASD: overlapping between Gidaya 2014, Hviid 2013; Sorensen 2013 and Liu 2017 (same dataset and period) => Liu was reported because larger study with an unexposed sick comparator. Low co-exposure SSRI/SNRI/TCA (<5%) => considered as monotherapies. | |
| The Danish National Prescription Registry (DNPR) that holds information on prescriptions filled, written by a general practitioner or medical specialist. | ||||||||
|
Talati (Controls unexposed, general pop) 2025 |
- |
unexposed (general population or NOS)
|
during pregnancy (anytime or not specified) | 820 / 863 | Only the result is extracted for potential retrieval at a later stage, as the outcome is not currently considered in metaPreg. | |||
|
Talati (Controls unexposed, sick) 2025 |
- |
unexposed, sick
|
during pregnancy (anytime or not specified) | 820 / 399 | Only the result is extracted for potential retrieval at a later stage, as the outcome is not currently considered in metaPreg. | |||
|
Ter Host (Controls exposed to TCA) 2013 |
The Netherlands 1995 - 2009 retrospective cohort (claims database) |
The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl | Children of mothers exposed to Serotonin reuptake inhibitors (SSRIs) during pregnancy. |
exposed to other treatment, sick
Children of mothers exposed to Tricyclic antidepressants (TCAs) during pregnancy. |
1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy | 436 / 67 | The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. Paroxetine (266), fluoxetine (111), citalopram (91), fluvoxamine (70), sertraline (34), and escitalopram (11). | |
| The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands. | ||||||||
|
Ter Host (Controls unexposed, NOS) 2013 |
The Netherlands 1995 - 2009 retrospective cohort (claims database) |
The ‘Pregnancy IADB’, extracted from the main pharmacy prescription database IADB.nl | Children of mothers exposed to Serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed (general population or NOS)
Children of mothers who did not use any selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) during pregnancy and during a period of 7 days before pregnancy. |
1st trimester, 2nd and/or 3rd trimester, at least 1st trimester, during pregnancy (anytime or not specified), throughout pregnancy | 436 / 35033 | The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group. Paroxetine (266), fluoxetine (111), citalopram (91), fluvoxamine (70), sertraline (34), and escitalopram (11). | |
| The pharmacy prescription database IADB.nl which contains pharmacy prescription data of an estimated population of 500 000 individuals from the Netherlands. | ||||||||
|
Toh a 2009 |
USA and Canada 1998 - 2007 retrospective cohort |
The Slone Epidemiology Center Birth Defects Study. | Pregnant women that receive selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy. |
unexposed (general population or NOS)
Pregnant women who did not receive selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy. |
at least 1st trimester | 92 / 5532 | Consideration of 'Continued SSRI exposure subjects' that were women treated with SSRIs 2 months before pregnancy who continued treatment after the first trimester. | |
| Within 6 months of delivery, trained nurses who were unaware of the study hypotheses conducted a 45- to 60-minute telephone interview with the participating mothers, notably to collect data regarding medications taken any time from 2 months prior to conception throughout pregnancy. | ||||||||
|
Toh b 2009 |
USA and Canada 1998 - 2008 retrospective cohort |
The Slone Epidemiology Center Birth Defects Study. | Pregnant women who used selective serotonin reuptake inhibitor (SSRI) only during pregnancy. |
unexposed (general population or NOS)
Pregnant women with no antidepressant use from 2 months before pregnancy through delivery. |
1st trimester, at least 1st trimester, during pregnancy (anytime or not specified) | 192 / 5710 | Consideration of women that remained on treatment beyond the first trimester (SSRI continuers). 'Women who used both SSRIs and non-SSRI antidepressants were excluded.'. | |
| Within 6 months of delivery, trained nurses who were unaware of the study hypotheses conducted a 45- to 60-minute telephone interview with the participating mothers, notably to collect data regarding medications taken any time from 2 months prior to conception throughout pregnancy. | ||||||||
|
Tran (Controls exposed to TCA) 2022 |
The Netherlands 2000 - 2010 retrospective cohort (claims database) |
The Netherlands Perinatal Registry (PERINED) and the PHARMO Database Network. | Pregnant women who received a dispensing of Selective serotonin reuptake inhibitors (SSRIs) between weeks 0–20 of gestation or received before pregnancy, but the treatment duration lasted into pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women who received a dispensing of tricyclic antidepressants (TCAs) between weeks 0–20 of gestation or received before pregnancy, but the treatment duration lasted into pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
1st and 2nd trimester, at least 1st trimester | 1488 / 214 | The RR provided by authors (for TCAs versus SSRI) not reported here because Fluoxetine excluded of SSRI class and no adjustment. | |
| The PHARMO Database Network, a population-based network of healthcare databases combining data from hospital and community pharmacies in the Netherlands, including the ATC classification of the drug, start and end date of use, strength, dosage regimen and route of administration. | ||||||||
|
Tran (Controls unexposed, NOS) 2022 |
The Netherlands 2000 - 2010 retrospective cohort (claims database) |
The Netherlands Perinatal Registry (PERINED) and the PHARMO Database Network. | Pregnant women who received a dispensing of Selective serotonin reuptake inhibitors (SSRIs) between weeks 0–20 of gestation or received before pregnancy, but the treatment duration lasted into pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who did not receive antidepressants in 15 months before delivery. |
1st and 2nd trimester, at least 1st trimester | 1488 / 95376 | ||
| The PHARMO Database Network, a population-based network of healthcare databases combining data from hospital and community pharmacies in the Netherlands, including the ATC classification of the drug, start and end date of use, strength, dosage regimen and route of administration. | ||||||||
|
Ulbrich 2021 |
USA 2017 - 2018 retrospective cohort |
Prentice Women’s Hospital of Northwestern University in Chicago, Illinois. | Third trimester maternal Selective serotonin reuptake inhibitor (SSRI) exposure. |
unexposed (general population or NOS)
No Selective serotonin reuptake inhibitor (SSRI) exposure. |
3rd trimester | 163 / 4770 | SSRI: fluoxetine (n = 20), sertraline (n = 96), citalopram (n = 14), escitalopram (n = 30), fluvoxamine (n = 1), and paroxetine (n = 2). | |
| Data were obtained through the electronic Enterprise Data Warehouse, which extracts information directly from the patient electronic health records. | ||||||||
|
Van der Veere 2020 |
The Netherlands 2007 - 2010 prospective cohort |
A prospective, longitudinal cohort design for the Dutch ‘SSRI in pregnant mothers, outcome of the kids’ study, abbreviated to SMOK. | Children who had been exposed to a selective serotonin reuptake inhibitors (SSRI) during pregnancy. |
unexposed (general population or NOS)
Children who had not been exposed to psychotropic medication during pregnancy, with adjustment for maternal psychopathology. |
during pregnancy (anytime or not specified) | 61 / 41 | Preterm, birth weight < P10, Apgar score ≤ 5 at 5 min not reported due to Overlapping with DeVries 2013. 'Venlafaxine was considered to work as an SSRI if given in low doses. Women taking < 200 mg venlafaxine were included in the SSRI group' | |
| Not specified (but prospective cohort). | ||||||||
|
Vasilakis-Scaramozza (Controls exposed to TCA) 2013 |
United Kingdom 1991 - 2002 retrospective cohort |
The United Kingdom’s General Practice Research Database (GPRD) containing data from 368 general practices. | Pregnant women with a diagnosis of depression and with at least one prescription for selective serotonin reuptake inhibitor (SSRI) during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period. |
exposed to other treatment, sick
Pregnant women with a diagnosis of depression and with at least one prescription for Tricyclic antidepressants during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period. |
1st trimester | 1825 / 1608 | 'Antidepressant exposure categories (tricyclics or SSRI) are not mutually exclusive.' but only 157 women were exposed to both tricyclics and SSRI (< 10%) => comparison between tricyclics and SSRI can be made. | |
| Clinical records that described prescribed drugs from each clinical visit. | ||||||||
|
Vasilakis-Scaramozza (Controls unexposed, NOS) 2013 |
United Kingdom 1991 - 2002 retrospective cohort (claims database) |
The United Kingdom’s General Practice Research Database (GPRD) containing data from 368 general practices. | Pregnant women with a diagnosis of depression and with at least one prescription for selective serotonin reuptake inhibitor (SSRI) during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period. |
unexposed (general population or NOS)
Pregnant women not exposed to any antidepressant during the first trimester of pregnancy. |
1st trimester | 1825 / 6617 | Overlapping of 'Congenital heart defects' with a larger study published by Margulis 2013, thus this outcome was not reported here. 'Women with exposure to other antidepressants in the first trimester of pregnancy were excluded from the analysis.' | |
| Clinical records that described prescribed drugs from each clinical visit. | ||||||||
|
Vial - Paroxetine 2006 |
France 1994 - 2005 prospective cohort |
A French multicentre prospective study (25 participating centers: pharmacovigilance and teratology information service). | Pregnant women exposed to paroxetine during early pregnancy (i.e. 3 to 10 weeks after the last menstrual period). |
unexposed (general population or NOS)
Pregnant women who were unexposed or exposed to a non-teratogenic agent during organogenesis. |
1st trimester | 683 / -9 | ||
| Maternal data and detailed history of drug exposures were collected during the first contact for individual risk counseling. | ||||||||
|
Viktorin 2017 |
Sweden 2005 - 2007 population based cohort retrospective |
A population-based cohort established by linkage of Swedish national registers. | Offspring born to mothers with at least 2 dispensations of selective serotonin reuptake inhibitor (SSRI) with medication periods that overlapped the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Offspring born to mothers without these medications use during pregnancy. |
during pregnancy (anytime or not specified) | 3178 / 172646 | ||
| The Swedish Prescribed Drug Register that contains information on all dispensed prescription medications in Sweden. | ||||||||
|
Viktorin b 2017 |
Sweden 2006 - 2014 population based cohort retrospective |
A birth cohort established by linkage of Swedish National registers. | Offspring that were born to mothers with at least 2 dispensations of selective serotonin reuptake inhibitors (SSRIs) overlapping the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Offspring that were born to mothers without any dispensation of an antidepressant with a medication period overlapping the pregnancy. |
during pregnancy (anytime or not specified) | 3178 / 172646 | Overlapping: Autism spectrum disorder not reported here because the same dataset was used for a larger study published by Sujan 2017. | |
| Dispensations identified in the Swedish Prescribed Drug Register that holds information on all dispensed prescription drugs in Sweden. | ||||||||
|
Wall-Wieler 2020 |
USA 2008 - 2015 retrospective cohort (claims database) |
The nationwide (American) IBM® MarketScan® Databases, a large administrative claims database. | Pregnant women having a Selective serotonin reuptake inhibitor (SSRI) prescription that had at least a 1-day supply in the 3 weeks after a woman’s estimated last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women who had a prepregnancy depression diagnosis and did not have Selective serotonin reuptake inhibitor (SSRI) prescription, but that could they could be exposed to an antidepressant (but not that class). |
early pregnancy | 28434 / 78354 | Non exposed group: a majority is non exposed to antidepressant (n=66501) whereas the other one are exposed to an other class of antidepressants. | |
| Antidepressant prescriptions were identified from outpatient pharmacy files through National Drug Codes (NDC) from outpatient pharmaceutical claims. | ||||||||
|
Wen 2006 |
Canada 1990 - 2000 retrospective cohort (claims database) |
Retrospective cohort study using the linked maternal/infant/prescription records from the Canadian province of Saskatchewan. | Pregnant women with at least 1 Selective serotonin reuptake inhibitor (SSRI) prescription that was dispensed in the 1-year period before delivery. |
unexposed (general population or NOS)
Pregnant women non exposed to Selective serotonin reuptake inhibitors (SSRIs) selected from the remainder of the database. |
3 months (or more) before pregnancy or during pregnancy | 972 / 3878 | Most of the patients used only 1 category of SSRI. No information related to other antidepressants. | |
| The Saskatchewan Health databases including prescription information. | ||||||||
|
Wichman 2009 |
USA 1993 - 2005 retrospective cohort |
A retrospective cohort study examining all medical records at Mayo Clinic’s site in Rochester, MN. | Mothers were treated with Selective serotonin reuptake inhibitors (SSRIs) at some point during their pregnancy. |
unexposed (general population or NOS)
All other women, i.e not exposed to Selective serotonin reuptake inhibitors (SSRIs). |
during pregnancy (anytime or not specified) | 808 / 24406 | Amon SSRI exposed women, 53 (6.6%) were exposed to a SRI (venlafaxine) | |
| The Division of Obstetrics prospectively maintains an obstetric deliveries database that was used to aid with the medical record review. The obstetric database listed the medications a woman took during her pregnancy. Each case was then confirmed by review of each individual medical record. | ||||||||
|
Wisner (Controls unexposed, disease free) 2009 |
USA 2000 - 2007 prospective cohort |
A prospective study with recruitment in Cleveland, Ohio, and Pittsburgh, Pennsylvania. | Pregnant women with major depressive disorder, treated with Selective serotonin reuptake inhibitor (SSRI) during the entirety of pregnancy or for the majority of each of the three trimesters. |
unexposed, disease free
Pregnant women with no exposure to any antidepressant or to major depressive disorder. |
throughout pregnancy | 48 / 131 | Overlapping: Wisner 2013 totally included in Wisner 2009. | |
| Maternal assessments were completed at weeks 20, 30, and 36 weeks of gestation. SSRI exposure was documented by charting each subject’s drug doses across each week of gestation. For inclusion in the SSRI-treated groups, exposure was confirmed with maternal serum level. | ||||||||
|
Wisner (Controls unexposed, sick) 2009 |
USA 2000 - 2007 prospective cohort |
A prospective study with recruitment in Cleveland, Ohio, and Pittsburgh, Pennsylvania. | Pregnant women with major depressive disorder, treated with Selective serotonin reuptake inhibitor (SSRI) during the entirety of pregnancy or for the majority of each of the three trimesters. |
unexposed, sick
Pregnant women with major depression throughout pregnancy or for the majority of each of the three trimesters, without Selective serotonin reuptake inhibitor (SSRI) treatment. |
throughout pregnancy | 48 / 14 | Overlapping: Wisner 2013 totally included in Wisner 2009. | |
| Maternal assessments were completed at weeks 20, 30, and 36 weeks of gestation. SSRI exposure was documented by charting each subject’s drug doses across each week of gestation. For inclusion in the SSRI-treated groups, exposure was confirmed with maternal serum level. | ||||||||
|
Wu 2019 |
USA 2000 - 2012 prospective cohort |
Right from the Start (RFTS), a community-based prospective cohort study from 8 metropolitan areas in North Carolina, Tennessee, and Texas. | Pregnant women reported any use of selective serotonin reuptake inhibitors (SSRIs) during their first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women who never used antidepressants during the first trimester of pregnancy. |
1st trimester | 179 / 5228 | 'Women with induced abortions and ectopic pregnancies were also excluded.' Exposure to SSRI considered as 'SSRI only' (because 95% (170/179) of SSRI only users). | |
| All women were assessed for antidepressant use in the first trimester interview, with an extensive telephone interview conducted near the end of the first trimester of pregnancy. | ||||||||
|
Yang 2021 |
Taiwan 2010 - 2016 retrospective cohort (claims database) |
The Health and Welfare Database (HWD) in Taiwan, administrative claims database that incorporates information from the Taiwan National Health Insurance Program, which covers more than 99.6% of Taiwan's population. | Pregnant women with depression and at least 1 prescription for an oral selective serotonin reuptake inhibitors (SSRI) from the day of pregnancy initiation up to the start of 20 weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with depression without antidepressant prescription. |
1st and 2nd trimester | 1547 / 2832 | 'In addition, we restricted the cohort of antidepressant users to patients who were only prescribed 1 consistent anti- depressant during the exposure period.' | |
| The Health and Welfare Database (HWD), administrative claims database that incorporates prescription drug utilization. | ||||||||
|
Yang (Controls unexposed, disease free) 2017 |
USA 2000 - 2011 prospective cohort |
Two National Institute of Mental Health–supported observational studies in Cleveland, Ohio, and Pittsburgh, Pennsylvania. | Pregnant women with a mood disorder (either major depressive or bipolar disorder) and who were taking an SRI but had no exposure to any antimanic drugs or benzodiazepines during pregnancy (the final 4 weeks of pregnancy). |
unexposed, disease free
Pregnant women who did not take psychotropics at any point during pregnancy and who did not have a major mood disorder. |
late pregnancy | 41 / 79 | The 41 SRI-exposed women were treated with SSRI (n=38) or venlafaxine (n = 3) => SSRI more than 90% => considered as SSRI group. Overlap with Wisner 2009 which include more pregnancies for preterm, neonatal intensive care, and Apgar (not reported here). | |
| Mothers belonged to one of 3 groups based on exposure status during pregnancy (NOS). | ||||||||
|
Yang (Controls unexposed, sick) 2017 |
USA 2000 - 2011 prospective cohort |
Two National Institute of Mental Health–supported observational studies in Cleveland, Ohio, and Pittsburgh, Pennsylvania. | Pregnant women with a mood disorder (either major depressive or bipolar disorder) and who were taking an SRI but had no exposure to any antimanic drugs or benzodiazepines during pregnancy (the final 4 weeks of pregnancy). |
unexposed, sick
Pregnant women with either mood disorder or bipolar disorder but who did not take psychotropic medications at any point during pregnancy. |
late pregnancy | 41 / 94 | The 41 SRI-exposed women were treated with SSRI (n=38) or venlafaxine (n = 3) => SSRI more than 90% => considered as SSRI group. Overlap with Wisner 2009 which include more pregnancies for preterm, neonatal intensive care, and Apgar (not reported here). | |
| Mothers belonged to one of 3 groups based on exposure status during pregnancy (NOS). | ||||||||
|
Yaris 2005 |
Turkey 1999 - 2004 prospective cohort |
Toxicology Information and Follow-up Service | Women who were exposed to Selective Serotonin Re-uptake Inhibitor (SSRIs) during pregnancy for depression, anxiety, and psychotic disorders. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Women who did not use any drug while pregnant. |
during pregnancy (anytime or not specified) | 54 / 248 | Addition of exposures to Fluoxetine (17), Sertraline (16), Fluvoxamine (9), Citalopram (7), Paroxetine (4) and escitalopram (1). Raw data for Intrauterine exitus not reported because the nb of cases in the unexposed group not clearly stated. | |
| Data surveyed by the interviews. | ||||||||
|
Yeh 2021 |
Taiwan 2002 - 2011 retrospective cohort (claims database) |
The Taiwan National Health Insurance Research Database (NHIRD). | Pregnant women with bipolar disorder receiving selective serotonin reuptake inhibitors (SSRI - fluoxetine, sertraline, citalopram, escitalopram, paroxetine, fluvoxamine) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with bipolar disorder not receiving any psychotropics before and during the pregnancy. |
1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified) | 163 / 5243 | For ADHD any trimester: inconsistency in OR and 95%CI provided by authors => Probable mistake: 2.30 [2.47; 3.62]: lower CI born < estimate => replace by 1.47 (instead of 2.47). | |
| The Taiwan National Health Insurance Research Database (THIRD) provides prescriptions information about insured individuals. | ||||||||
|
Zakiyah 2018 |
The Netherlands 1994 - 2015 retrospective cohort (claims database) |
A retrospective cohort study performed with a large mother-infant subset from the University of Groningen’s IADB.nl pharmacy prescription database, referred to as 'pregnancy database'. | At least one dispensing record of selective serotonin reuptake inhibitors (SSRIs) between the theoretical conception date and 20 completed weeks of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnant women that were without antidepressant prescriptions in the period of 6 months prior to the theoretical conception date until 20 completed weeks of gestation. |
1st and 2nd trimester | 394 / 27481 | Among the 539 exposure antidepressants as a whole, about 3% have co-exposure of different class of antidepressants => Considered as monotherapy of TCAs, SSRIs, .... | |
| The University of Groningen’s IADB.nl pharmacy prescription database, a longitudinal database containing pharmacy-dispensing data from community pharmacies in the Netherlands. | ||||||||
|
Zeskind 2004 |
USA Not specified retrospective cohort |
The Carolinas Medical Center in Charlotte, North Carolina, USA. | Newborn infants whose mothers used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
unexposed (general population or NOS)
Newborn infants whose mothers who did not use selective serotonin reuptake inhibitors (SSRIs) during pregnancy. |
throughout pregnancy | 17 / 17 | All mothers continued taking SSRIs up to labor and delivery, except for 1 mother who reported that she stopped taking Zoloft late in the third trimester. | |
| Used SSRIs during pregnancy determined according to medical records. | ||||||||
| Study | Country Study period Study design |
Data source | Case | Control | Exposition | Exposition period | Sample size (exposed/unexposed) Or (case / control) |
Remarks | Risk of bias |
|---|---|---|---|---|---|---|---|---|---|
|
Alwan 2007 |
USA 1997 - 2002 case control |
The National Birth Defects Prevention Study (NBDPS). | The case infants were infants born alive or died at 20 SG or more and who had received a diagnosis of at least one selected birth defect. | The controls were live-born infants with no major birth defects who were randomly selected from hospital or state birth-certificate records from the same geographic areas. | Information on exposure to SSRIs and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants conducted in English or Spanish. | 1st trimester | 9622 / 4092 | Overlapping: Major Malformations and individual malformations not reported because updated by Anderson 2020. 'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.' | |
| Case infants were ascertained through population-based birth-defects surveillance systems in eight U.S. states. Controls were selected randomly from the same geographic areas. Information on the case infants was reviewed by clinical geneticists unaware of the infants’ exposure status | |||||||||
|
Ames (Controls unexposed, disease free) 2021 |
USA 2003 - 2011 case control |
The Study to Explore Early Development (SEED): a multisite case-control study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network. | Children with Autism spectrum disorder (ASD) or with other developmental delays or disorders (DDs) such as language delay or intellectual disability (ID) recruited from educational and clinical settings that serve children with developmental disorders. | Children from the general population randomly sampled state birth records at each study site who either scored <11 on the SCQ or scored >=11 but did not meet ASD criteria after the in-person assessment. | Maternal use of SSRIs during pregnancy were ascertained from all participants in three ways: self-report in a telephone interview shortly after study enrollment (SEED Caregiver Interview), self-report on the SEED maternal medical history form, and abstraction from prenatal medical records. | 1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified), preconception-only | 1750 / 1671 | The final analytic sample comprised 1367 children with ASD, 1750 with DDs, and 1671 POP controls. No age specified in article but in CDC website: 'The study will include children with ASD, with other DDs, and with typical development, ages 2-5 years'. | |
| Children completed a multistage process. 1) Mother (mainly) completed the Social Communication Questionnaire. 2) Gold standard clinical assessments: Autism Diagnostic Observation Schedule, Autism Diagnostic Interview Revised, Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales. | |||||||||
|
Ames (Controls unexposed, sick) 2021 |
USA 2003 - 2011 case control |
The Study to Explore Early Development (SEED): a multisite case-control study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network. | Children with Autism spectrum disorder (ASD) or with other developmental delays or disorders (DDs) such as language delay or intellectual disability (ID) recruited from educational and clinical settings that serve children with developmental disorders. | Children from the general population randomly sampled state birth records at each study site who either scored <11 on the SCQ or scored >=11 but did not meet ASD criteria after the in-person assessment. | Maternal use of SSRIs during pregnancy were ascertained from all participants in three ways: self-report in a telephone interview shortly after study enrollment (SEED Caregiver Interview), self-report on the SEED maternal medical history form, and abstraction from prenatal medical records. | 1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified), preconception-only | 329 / 328 | The final analytic sample comprised 1367 children with ASD, 1750 with DDs, and 1671 POP controls. No age specified in article but in CDC website: 'The study will include children with ASD, with other DDs, and with typical development, ages 2-5 years'. | |
| Children completed a multistage process. 1) Mother (mainly) completed the Social Communication Questionnaire. 2) Gold standard clinical assessments: Autism Diagnostic Observation Schedule, Autism Diagnostic Interview Revised, Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales. | |||||||||
|
Anderson 2020 |
USA 1997 - 2011 case control |
The National Birth Defects Prevention Study (NBDPS), a US population-based, multisite case-control study. | The case infants were infants born alive or died at 20 SG or more and who had received a diagnosis of at least one selected birth defect. | The controls were live-born infants with no major birth defects who were randomly selected from hospital or state birth-certificate records from the same geographic areas. | Information on exposure to SSRIs and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants, conducted 6 weeks to 24 months after the EDD. | 1st trimester | 30630 / 11478 | Overlapping: this study is an update of Alwan 2007, Nembhard 2017, Werler 2018 (gastroschisis) and Lind 2013 (hypospadias). 'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.' | |
| Case infants were ascertained through population-based birth-defects surveillance systems in 10 U.S. states. Controls were selected randomly from the same geographic areas. Clinical data were abstracted from medical records and classified by clinician geneticists and other clinicians. | |||||||||
|
Bakker - Paroxetine 2010 |
The Netherlands 1997 - 2006 case control |
The EUROCAT Northern Netherlands database, a population-based birth defects registry for the northern part of the Netherlands. | Fetuses or children born with isolated congenital heart defects (included fetuses or children with simple or complex heart defects only and excluded fetuses or children with associated genetic or other syndromes or those with extracardiac malformations.) | Fetuses and children with a chromosomal or single gene disorder as controls (with exclusion of children with an associated heart defect ) | Information regarding medications dispensed before and during pregnancy is obtained from community pharmacies which keep complete records of dispersed medications. The use of the prescribed medications and the use of over-the-counter medication is verified in a telephone interview with the mother. | 1st trimester | 678 / 615 | Overlapping with Wemakor 2015, a larger study based on 12 EUROCAT registries (included The Netherlands) for VSD, ASD, septal defects and cardiac malformations. Results not reported here. | |
| The registry is notified of infants and fetuses with a congenital malformation by physicians and midwifes on a voluntary basis. Reports are actively collected from obstetric, pediatric, pathology, cytogenetic departments. Data on malformations is obtained from the medical files and is coded (ICD). | |||||||||
|
Boyle 2017 |
12 European countries (DK, FR, NL, SW, MT, BE, DE, UA, IR, IT, UK, SP) 1982 - 2011 case control |
15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries (EUROCAT). | Cases of Ebstein’s anomaly (live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy). | Cases of Non-cardiac anomaly (live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy). | Most sources of exposure data were prospective to outcome, except in one centre where exposure data are ascertained exclusively by interviewing mothers and clinicians after the congenital anomaly has been diagnosed; three other registries use maternal interviews to confirm their data. | 1st trimester | 173 / 51024 | Exclusion of teratogenic syndrome in both cases and controls. Exclusion of cases and controls exposed to diabetes. | |
| EUROCAT registries that record all cases of major congenital anomalies among live births, foetal deaths ≥20 weeks’ gestation and termination of pregnancy for foetal anomaly (TOPFA), in their populations using International Classification of Diseases (ICD)-9/10. | |||||||||
|
Chambers 2006 |
USA and Canada 1998 - 2003 nested case control |
The Birth Defects Study of the Slone Epidemiology Center. | Mothers of subjects with Persistent pulmonary hypertension of the newborn (PPHN). | Mothers of subjects without Persistent pulmonary hypertension of the newborn (PPHN). | Within 6 months of delivery, trained study nurses who were unaware of the study hypothesis interviewed all the mothers. The structured telephone interview included questions on the use of all medications (prescription and over-the-counter) from 2 months before conception to the end of the pregnancy. | 2nd and/or 3rd trimester, during pregnancy (anytime or not specified), early pregnancy | 377 / 836 | ||
| Admission and discharge records from major referral hospitals and clinics were reviewed, logbooks from neonatal intensive care units were examined, and weekly telephone calls were made to collaborators at newborn nurseries in community hospitals. | |||||||||
|
Clements 2015 |
USA 1997 - 2010 case control |
The Partners HealthCare electronic health record (EHR) from a large Massachusetts health-care system. | Infants who had at least one ICD-9 code of 299 (pervasive developmental disorder) or with ICD-9 code of 314.x (attention-deficit hyperactivity disorder (ADHD)). | Infants not having any prior history of Autism Spectrum Disorder (ASD), attention-deficit hyperactivity disorder (ADHD) or intellectual disability (ICD9 of 299, 314 or 317–319). | The Partners HealthCare EHR includes medication data. | 1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified), early pregnancy, preconception-only | 2243 / 5631 | 1377 children with ASD matched to 4022 healthy control children and 2243 with ADHD (but no ASD diagnosis) matched to 5631 healthy control children. | |
| The Partners HealthCare EHR includes sociodemographic data, billing codes, laboratory results, problem lists, vital signs, procedure reports and narrative notes from hospitals which are part of the Partners HealthCare system, and affiliated outpatient clinics. | |||||||||
|
Croen 2011 |
USA 1995 - 1999 nested case control |
The Childhood Autism Perinatal Study, a large case-control study within the Kaiser Permanente Medical Care Program in Northern California. | Children with at least 1 diagnosis of autism (ICD-9-CM code 299.0), Asperger syndrome (ICD-9-CM code 299.8), or pervasive developmental disorder not otherwise specified (ICD-9-CM code 299.8). | Children without an Autism spectrum disorder diagnosis randomly sampled from the remaining cohort of live births. | All inpatient and outpatient prescriptions for antidepressants dispensed at a KPNC pharmacy in the 3 months before the last menstrual period (LMP) through the date of delivery of the study child were identified from the Pharmacy Information Management System. | 1st trimester, 2nd trimester, 3 months (or more) before pregnancy or during pregnancy, 3rd trimester, preconception-only | 298 / 1507 | Analysis restricted to the subgroup of women with a history of a mental health not reported from this study because the only one considered exposure is 3 months before pregnancy or during pregnancy. | |
| On the basis of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) recorded in the KPNC outpatient clinical databases. | |||||||||
|
Dandjinou 2019 |
Canada 1998 - 2015 nested case control |
The Quebec Pregnancy Cohort (QPC), a Canadian provincial database. | Pregnant women with a diagnosis of gestational diabetes mellitus (GDM) identified using diagnosis codes ICD-9: 250.0–250.9, 648.0, 648.8, 790.2, 775.1 or ICD-10: E10–E14, O24, R73.0) or at least one filled prescription for an antidiabetic drug allowed during pregnancy (insulin, glyburide or metformin), both after week 20 of gestation, whichever occurred first. | Pregnant women that did not have a diagnosis of gestational diabetes mellitus (GDM) at the index date. | The Quebec Prescription Drug Insurance Database (drug name, start date, dosage and duration). | during pregnancy (anytime or not specified) | 20905 / 209050 | The 10 categories of exposure were mutually exclusive. | |
| The medical service database (RAMQ: diagnoses and medical procedures), the Hospitalisation Archive Database (MedEcho: in-hospital diagnoses and procedures) and the Quebec Statistics Database (Institut de la statistique du Québec (ISQ):patient sociodemographic information). | |||||||||
|
Dave 2019 |
USA 2011 - 2015 nested case control |
The IBM MarketScan commercial claims database, an employer- sourced health insurance database. | Neonatal abstinence syndrome (NAS) in live births. | No neonatal abstinence syndrome (NAS) in live births. | The IBM MarketScan commercial claims database, an employer-sourced health insurance database. | 3rd trimester | 659 / 621281 | ||
| Neonatal abstinence syndrome deliveries were identified using in- and outpatient encounters with the ICD-9 code 779.5 within 30 days of delivery date in either the infant or mother’s medical encounter files. | |||||||||
|
De Jonge - Paroxetine only 2013 |
The Netherlands 1998 - 2008 case control |
EUROCAT NNL, a population-based birth defect registry in the northern part of the Netherlands and the IADB pregnancy database. | All malformed foetuses and children (live births, stillbirths, spontaneous abortions and terminations of pregnancy) excluding chromosomal and genetic disorders. | From the IADB, a population-based prescription database that contains prescription data from approximately 55 community pharmacies in The Netherlands, we selected the population controls. The IADB covers an estimated population of 500,000 individuals, which is considered representative of the general population. | For controls: from the IADB, a population-based prescription database. For cases: the pharmacy records for 3 months before conception until delivery were obtained and verified in a telephone interview and only the actually used medication is registered. | 1st trimester | 3212 / 29223 | Overlapping with Wemakor 2015, a larger study based on 12 EUROCAT registries (including The Netherlands) for cardiac, respiratory and digestive malformations => not reported here. Several SSRIs studied => To avoid redundancy of control, use of paroxetine. | |
| Information on congenital malformations is obtained from the medical files, including pathology reports, and coded afterwards, according to the International Classification of Diseases (ICD) coding system by trained registry staff. | |||||||||
|
De Vera 2012 |
Canada 1997 - 2003 nested case control |
The Quebec Pregnancy Registry (QPR), a longitudinal cohort established with the linkage of three administrative databases. | Women with a diagnosis of gestational hypertension (ICD-9: 642.3, 642.0), pre-eclampsia (ICD-9: 642.4, 642.5) or eclampsia (ICD-9: 642.6) after the 20th week of gestation. | Women who did not have a diagnosis of pregnancy-induced hypertension at or before the same gestational age. | The Quebec’s Public Prescription Drug Insurance Plan. | during pregnancy (anytime or not specified) | 1216 / 12160 | ||
| Linkage of three administrative databases: (i) Régie de l’Assurance Maladie du Québec (RAMQ), (ii) MED-ECHO and (iii) Institut de la Statistique du Québec (ISQ). | |||||||||
|
Eriksson 2012 |
Sweden 2002 – 2006 case control |
A population-based group of children of the Autism Centre for Young Children in Stockholm and the Swedish medical birth register (SMBR). | Children with a clinical diagnosis of Autism spectrum disorders (ASD). | All children born alive in Stockholm County, excluding children with a clinical diagnosis of ASD in the county. | Data on maternal pre- and intrapregnancy medication were collected from the Swedish medical birth register (SMBR) and the Statistical Central Bureau of Sweden. | during pregnancy (anytime or not specified) | 188 / 173390 | ||
| All children were assessed by one of four medical doctors in the research team. The parents were comprehensively interviewed according to a structured protocol regarding first-degree relatives with ASD and other neurodevelopmental problems and/or a history of psychiatric disorder. | |||||||||
|
Given 2017 |
14: Belgium, Croatia, Denmark, FR, Germany, Ireland, Italy, Netherlands, Norway, Ukraine, UK... 1995 - 2012 case control |
A case-malformed control study based on EUROmediCAT, a population based reproductive pharmacovigilance system, based on the European Surveillance of Congenital Anomalies (EUROCAT) network. | Infants with gastroschisis (ICD-9 with BPA extension code 75671 or ICD-10 code Q793). | Infants with a diagnosis of a major congenital anomaly not including gastroschisis. | First trimester maternal medication exposures were mostly obtained by registries from prospectively recorded maternity records. Additional data sources included the medical records of the infant, general practitioner records, maternity passports, and maternal interviews before or after birth. | 1st trimester | 1587 / 154877 | Overlapping; this study updated Wemakor 2015 for gastroschisis. Medications taken in the second or third trimester or where the timing was unknown were excluded. | |
| EUROCAT registries that record all cases of major congenital anomalies among live births, foetal deaths ≥20 weeks’ gestation and termination of pregnancy for foetal anomaly (TOPFA), in their populations using International Classification of Diseases (ICD)-9/ | |||||||||
|
Granstrom 2019 |
Sweden 2006 - 2012 nested case control |
A Swedish nationwide, population-based, case–control cohort study | All cases with an ICD code for Hirschsprung disease (HSCR) (ICD-8, 751.39; ICD-9, 751D; ICD-10: Q431). | Neonates without a history of Hirschsprung disease (HSCR). | The exposure was assessed through the Swedish Prescribed Drug Register for both cases and their mothers, that contains information on drug identity (Anatomical Therapeutic Chemical (ATC) codes) and dates of all registered prescriptions to the entire population in Sweden. | 3 months (or more) before pregnancy or during pregnancy | 150 / 750 | ||
| The outcome was assessed through linkage with the Swedish National Patient Register (NPR) and the Swedish Medical Birth Register (MFR) for both cases and their mothers. The International Classification of Diseases (ICD) codes was used. | |||||||||
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Harrington 2014 |
USA 2003 - 2010 case control |
The Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population- based case-control study. | Children with autism spectrum disorders (ASDs), with developmental delays (DDs) other than ASD. | Children with typical development. | A standardized telephone interview was conducted with the child’s biological mother to collect exposures for an index period covering 3 months before conception to the end of pregnancy or through breastfeeding. Prenatal medical records were used, when available, to supplement self-reported SSRI use. | 1st trimester, 2nd trimester, 3rd trimester, during pregnancy (anytime or not specified) | 646 / 320 | ||
| Children with ASD and DD were identified from those qualifying for specific services. To confirm ASD diagnoses, children were assessed with the Autism Diagnostic Interview–Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) by trained staff with reliability on the instruments. | |||||||||
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Hartwig 2022 |
The Netherlands 1995 - 2016 case control |
The IADB.nl database, a prescription database from the University of Groningen in the Netherlands. | Children receiving at least two consecutive prescriptions for Attention-deficit/hyperactivity disorder (ADHD) medication (i.e., methylphenidate, dextroamphetamine, or atomoxetine) before the age of 16, with 'consecutive' meaning the second prescription being received within 6 months. | Sibling of a case, being born from the same womb, with no prescriptions for MPH, dextroamphetamine, or atomoxetine during follow-up until the 16th birthday. | Prescription database that contains prescription records include data on the date of dispensing, the amount dispensed, the dose regimen, the number of days the prescription is valid, the prescribing physician, and the Anatomical Therapeutic Chemical (ATC) code. | during pregnancy (anytime or not specified) | 1304 / 1529 | ||
| Drug prescription data was used as a proxy for Attention-deficit/hyperactivity disorder (ADHD) in offspring, as diagnostic information was not available: methylphenidate (MPH), dextroamphetamine or atomoxetine. | |||||||||
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Kawai 2023 |
Japan 2011 - 2014 nested case control |
The Japan Environment and Children’s Study (JECS), a large-scale birth cohort study that has enrolled more than 100000 pregnant women and their offspring in Japan. | Child having a Congenital Heart Defect (CHD), i.e physicians reported at birth, 1 month, 6 months, age 1 year, or 2 years that the child had CHD in the questionnaires. | Child that did not have a Congenital Heart Defect (CHD). | All data for exposures were obtained during the first and second trimester of pregnancy. Data on children and the environment obtained using self-administered questionnaires completed by caregivers and data recorded at the time of delivery by a physician. | early pregnancy | 1264 / 90400 | ||
| Data on children and the environment obtained using self-administered questionnaires completed by caregivers and data recorded at the time of delivery by a physician. | |||||||||
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Kerr 2018 |
USA and Canada 1993 - 2015 case control |
Slone Epidemiology Center Birth Defects Study (BDS) | Infants with microcephaly alone (“isolated”) and microcephaly that included other major birth defects (“non-isolated”), | Nonmalformed live-born infants. | Within 6 months of delivery, trained Birth Defects Study (BDS) nurse- interviewers contacted mothers to complete a roughly 1-hr computer-assisted telephone interview, including medications during pregnancy. | 1st trimester, 2nd trimester, 3rd trimester | 166 / 12059 | Authors analyzed separately “isolated” microcephaly and “non-isolated” microcephaly. Only isolated microcephaly are indexed in MetaPreg. | |
| Cases and controls were ascertained at participating hospitals or birth defect registries in the same areas. | |||||||||
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Kieler 2015 |
Denmark, Finland, and Norway 1996 - 2007 nested case control |
National registers of Denmark, Finland, and Norway. | Women with elective termination of pregnancy at 12–23 weeks of gestation. | Women that continued their pregnancy, randomly selected and matched with cases on key factors. | The prescription registers include data on dispensed item, substance, brand name, and formulation, together with date of dispensing for over 95% of the total outpatient population. | 3 months (or more) before pregnancy or during pregnancy, during pregnancy (anytime or not specified) | 14902 / 148929 | SSRIs (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, and escitalopram). The (ORs) are presented for women exposed to only one type of antidepressant during the exposure period. | |
| In the registers the diagnoses and pregnancy complications are classified according to the national version of the International Classification of Diseases (ICD). | |||||||||
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Kitchin 2022 |
Spain 2002 - 2015 case control |
The Spanish database BIFAP (Base de Datos para la Investigacion Farmacoepidemiologica en Atencion Primaria, Database for Pharmacoepidemiological Research in Primary Care) | Pregnant woman suffering a miscarriage. | Pregnant woman randomly selected from the whole cohort among women who were still at risk within follow-up, by risk-set sampling and individually matched to cases. | Database for Pharmacoepidemiological Research in Primary Care, a computerized medical longitudinal population database of electronic medical records from 10.153 primary care practitioners and pediatricians distributed on nine Autonomous Regions (out of 17), which contains prescriptions. | 1st trimester | 18070 / 54209 | ||
| Database for Pharmacoepidemiological Research in Primary Care, a computerized medical longitudinal population database of electronic medical records from 10.153 primary care practitioners and pediatricians, which contains medical diagnoses, medical visits, hospital admissions. | |||||||||
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Laspro - Sertraline 2024 |
USA 2013 - 2023 nested case control |
EPIC Cosmos, a database incorporating health information of 180 million patients, throughout the United States from approximately 180 US institutions utilizing EPIC medical records. | Newborns with oral clefts (ICD 10 codes Q35 or Q36 or Q37). | Newborns without oral clefts. | Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy. | during pregnancy (anytime or not specified) | 12098 / -9 | Laspro et al provided results for several SSRIs => to avoid redundancy of controls, only one can be used => this one with more exposed pregnancies (i.e Sertraline). | |
| Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records. | |||||||||
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Louik 2007 |
USA and Canada 1993 - 2004 case control |
The Slone Epidemiology Center Birth Defects Study. | Infants with any of a wide range of malformations with exclusion of isolated minor defects (e.g., accessory nipples, dislocatable hips, and low-set ears). | Nonmalformed infants. | Detailed data are collected on all medications (prescription, over-the-counter, vitamins and minerals, and herbal products) used at any time from 2 months before conception through the end of the pregnancy, by mother completion of a 45-to-60-minute interview within 6 months after delivery. | 1st trimester | 9849 / 5860 | Exclusion of subjects whose infants had chromosomal defects, known mendelian inherited disorders, syndromes, defects with a known cause (e.g., fetal alcohol syndrome), and metabolic disorders. Overlapping: Conotruncal defects (Louik 2014). | |
| Research staff identify subjects by reviewing clinical and surgical logs, reviewing admission and discharge lists, and contacting newborn nurseries and labor and delivery rooms. Nonmalformed infants were identified in a population-based random sample of newborns in Massachusetts. | |||||||||
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Louik 2014 |
USA and Canada 1992 - 2011 case control |
The Slone Epidemiology Center’s Birth Defects Study (BDS), a multi-center case-control surveillance program for birth defects. | Infants with any of a wide range of malformations (infants with isolated minor defects are excluded).. | Infants without malformations. | Mothers are invited to participate in a telephone interview after delivery, conducted by trained nurses who are unaware of the study hypotheses. It collects detailed data on all medications (prescription, over-the-counter, ...) used anytime from 2 months prior to conception through the pregnancy. | 1st trimester | 2734 / 8611 | ||
| Research staff identify malformed subjects by reviewing hospital admission and discharge lists or from statewide birth-defect registries and mothers of non-malformed infants were identified at study hospitals and from a population-based random sample of newborns in Massachusetts. | |||||||||
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Man 2015 |
Hong Kong 2001 - 2014 case control |
The Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System. | Children diagnosed with autism spectrum disorder (ASD). | Children without diagnosis of autism spectrum disorder (ASD). | Electronic medical records on the Clinical Data Analysis and Reporting System. | during pregnancy (anytime or not specified) | 4208 / 292758 | 299 672 children included in the analysis. 4208 and 2706 children were diagnosed with ASD and ADHD, respectively. Results of ADHD not reported here, because a more detailed article was published by the same authors (Man 2017) related specifically to ADHD. | |
| Electronic medical records on the Clinical Data Analysis and Reporting System. | |||||||||
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Nakhai-Pour 2010 |
Canada 1998 - 2003 nested case control |
The Quebec Pregnancy Registry, built with the linkage of three administrative databases: the Régie de l’assurance maladie du Québec (RAMQ), the Med-Echo database and the Institut de la statistique du Québec database. | Pregnant women with a diagnosis or a procedure for spontaneous abortion between the first day and the 20th week of gestation. | Randomly selected pregnant women who did not have a spontaneous abortion at or before the same gestational age as their matched case did. | The Régie de l’assurance maladie du Québec (RAMQ) database which provides prospectively collected data on filled prescriptions. | during pregnancy (anytime or not specified) | 5124 / 51240 | ||
| The Régie de l’assurance maladie du Québec (RAMQ) (physician-based diagnoses according to the ICD-9), the Med-Echo database (data on acute care hospital admissions) and the Institut de la statistique du Québec database (data on all births and deaths in Quebec). | |||||||||
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Neo 2020 |
USA 2010 - 2016 case control |
A tertiary care hospital, Beth Israel Deaconess Medical Center, Boston, MA, USA | Infants treated with therapeutic hypothermia for concern for hypoxic ischemic encephalopathy (HIE). | Controls were the next four noncase deliveries within 6 months of the case. | To determine whether infants were prenatally exposed to SSRIs, two investigators (DTN and EN) independently reviewed each maternal chart, blinded as to whether the infants received therapeutic hypothermia. | during pregnancy (anytime or not specified) | 38 / 148 | ||
| Cases were identified from the electronic medical record. Controls were the next four noncase deliveries within 6 months of the case. | |||||||||
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Ogawa 2018 |
Japan 2005 - 2014 nested case control |
Claims data supplied by the Japan Medical Data Center (JMDC) Ltd, Tokyo Japan. | Mothers who had experienced preterm birth or had given birth to a low birth weight infant. | Mothers who had neither experienced preterm birth nor had given birth to a low birth weight infant, as recorded in the claims data. | For each person, the Japan Medical Data Center (JMDC) database includes prescriptions. The classification of drugs is based on the Anatomical Therapeutic Chemical classification system of the European Pharmaceutical Market Research Association. | 2nd and/or 3rd trimester | 1615 / 40224 | Selective serotonin reuptake inhibitors: escitalopram, fluvoxamine, paroxetine, and sertraline. | |
| For each person, the Japan Medical Data Center (JMDC) database includes an encrypted personal identifier, age, gender and diagnoses. | |||||||||
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Salkeld 2008 |
Canada 1999 - 2005 nested case control |
A population-based nested case-control study using 4 linked administrative databases in Ontario, Canada | Pregnant women with a delivery complicated by postpartum hemorrhage. | Pregnant women with a delivery uncomplicated by postpartum hemorrhage. | Prescription records identified using the Ontario Drug Benefit (ODB) database, which included comprehensive records of all prescription medications dispensed to Ontario residents receiving social assistance. | 2nd and/or 3rd trimester, 3rd trimester, late pregnancy | 2460 / 23943 | ||
| The Canadian Institute for Health Information Discharge Abstract Database, and the Ontario Health Insurance Plan database were used to identify claims for hospital visits and inpatient and outpatient physician services. | |||||||||
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Solé 2020 |
Spain 2005 - 2017 nested case control |
The Perinatal Mental Health Unit in a general university hospital (Hospital Clinic of Barcelona) | Pregnant women who had a C-Section (C-Section group). | Pregnant women who had a vaginal delivery (non-C-Section group). | Women were followed throughout pregnancy by a clinical researcher, who recorded the type and dosage of medications during pregnancy and information about concurrent medical illness. | during pregnancy (anytime or not specified) | 40 / 60 | ||
| Obstetric and medical histories were obtained for all women by systematic review of obstetric records and prenatal care. | |||||||||
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Wemakor 2015 |
Belgium, Spain, Ireland, Malta, Netherlands, Norway, Denmark, FR, Germany, Italy, Switzerland, UK 1995 - 2009 case control |
Case-malformed control study based on 12 population-based European Surveillance of Congenital Anomalies (EUROCAT) congenital anomaly registries. | Babies with congenital heart defects (CHD) or with congenital anomalies other than CHD identified as significantly associated with SSRI exposure (‘‘signals’’) in at least one previous study. | All other registrations. | Medication exposure information came from maternal medical/midwifery notes, created prospectively. Other additional data sources include paediatrician records (postnatal), medical geneticist records (postnatal), GP records of mother (prenatal), and maternal interviews (postnatal). | 1st trimester | 12876 / 17083 | Overlapping: for gastroschisis and Ebstein's anomay, Given 2017 and Boyle 2017 published an updated and larger study based on EUROCAT data (thus these outcomes not reported here). | |
| EUROCAT registries collect data using multiple sources of information: maternity, neonatal, and paediatric records; fetal medicine, cytogenetic, pathology, and medical genetics records; paediatric cardiology services; and hospital discharge and child health records. ICD 9 or 10 classification. | |||||||||
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Wilson 2011 |
USA 2003 - 2009 case control |
Madigan Army Medical Center’s comprehensive electronic medical records (EMR) system. | Neonates born at >34 weeks gestation and verified to have primary Persistent pulmonary hypertension of the newborn (PPHN). | The next six births of cases occurring at the same gestational age in weeks were identified from the hospital’s delivery log. | Prescription medication use was captured in three ways: a computerized database of all medications filled in our system; review of each patient’s outpatient antepartum electronic medical records (EMR); and review of each patient’s inpatient EMR generated at the time of admission for delivery. | 2nd and/or 3rd trimester | 20 / 120 | Neonates with congenital anomalies known to cause pulmonary hypertension (e.g., diaphragmatic hernia) were excluded. Cases of meconium aspiration syndrome and neonatal pneumonia and sepsis were also excluded. | |
| Review of electronic medical records. The records of all infants who were diagnosed with PPHN were reviewed by an experienced neonatologist. | |||||||||
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Yazdy 2014 |
USA 2006 - 2011 case control |
The Slone epidemiology center at Boston University, a population-based case-control study, based on registries in Massachusetts, north carolina, and new York. | Infants with a diagnosis of talipes equinovarus ('clubfoot') without a known syndrome. | Infants with no major malformations or foot problems, drawn from the same birth population as cases and selected from either birth certificates (Massachusetts and north carolina) or hospital medical records (new York). | The telephone interview were conducted by trained nurses within 1 year after delivery. It consisted in questions notably on illnesses and medications. If a mother reported using any medications, the timing and indication for use were noted. | 1st trimester | 622 / 2002 | No overlapping between Yazdy 2014 (2006 - 2011) and Louik 2007 (1993 - 2004). | |
| Diagnosis of structural clubfoot was confirmed primarily by orthopedic records (77%); when medical records were not available, maternal report of 3 or more castings for the clubfoot was used to confirm a true structural clubfoot (23%). | |||||||||
Risk of bias: : NA; : low; : moderate; : serious; : critical; : unclear;
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