Paroxetine

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Andersen, 2014	Denmark 1997 - 2010	All pregnancies in Denmark during the study period.	Pregnant women dispensing of a prescription of Paroxetine (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.	2739 / 1256956
Ban (Controls unexposed, disease free), 2014	United Kingdom 1990 - 2009	All singleton live births for women aged 15– 45years in which the medical records of the mothers and the children were linked to provide prospectively recorded information throughout pregnancy and in the year before pregnancy.	Pregnant women with Paroxetine 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.	1200 / 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 and antipsychotic drugs before childbirth.
Ban (Controls unexposed, sick), 2014	United Kingdom 1990 - 2009	All singleton live births for women aged 15– 45years in which the medical records of the mothers and the children were linked to provide prospectively recorded information throughout pregnancy and in the year before pregnancy.	Pregnant women with Paroxetine 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 diagnosed depression (in the year before conception up to the end of the first trimester) but with no antidepressant drug prescriptions in the first trimester.	1200 / 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 and antipsychotic drugs before childbirth.
Bérard, 2017	Canada 1998 - 2009	Pregnancies with continuous prescription drug insurance coverage of at least 12 months before the 1DLMP and during pregnancy; pregnancies with a diagnosis of depression and/or anxiety or exposed to antidepressants in the 12 months before pregnancy.	Depressed/anxious pregnancies with prescription fillings for Paroxetine dispensed during the first trimester of gestation.	unexposed, sick Depressed/anxious pregnancies with no exposure to any antidepressants during the first trimester of gestation.	1132 / 14847	Overlapping: results of Ramos 2008 (1998-2002) are included in this larger study.
Bérard, 2016	Canada 1998 - 2009	All full-term (≥37 weeks’ gestation) singleton infants born during the study period and whose mothers were covered by the RAMQ drug plan for at least 12 months before and during pregnancy.	Pregnant women having at least 1 prescription of Paroxetine filled at any time during the second/third trimester of pregnancy. (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 at any time throughout gestation.	744 / 142716	Material and methods based on description provided by Boukhris et al 2016.
Brown, 2017	Canada 2002 - 2010	Singleton children born in Ontario hospitals whose mothers were between the ages of 16 and 50 years and eligible for public drug benefits during pregnancy.	Pregnant women with 2 or more consecutive prescriptions for paroxetine 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.	577 / 33069
Calderon-Margalit, 2009	USA 1996 - nr	Pregnant mothers who initiated prenatal care before 20 weeks’ gestation and planned to deliver at either one of the two study hospitals.	Pregnant women who used Paroxetine 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.	31 / 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.
Chan (Controls exposed to TCA), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	Infants of women with prescription of Paroxetine 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 with prescription of Tricyclic antidepressants (TCA) only filled during the first trimester and prescriptions filled before pregnancy but with duration overlapping the first trimester.	48 / 322
Chan (Controls unexposed, pop general), 2024	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals between January 1, 2003 and December 31, 2018.	Infants of women with prescription of Paroxetine 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.	48 / 462377
Colvin, 2011	Australia 2002 - 2005	All births in Western Australia during the study period.	Pregnant women who were dispensed Paroxetine 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).	676 / 92995
Colvin, 2012	Australia 2002 - 2005	All births in Western Australia during the study period.	Children born to women who had been dispensed Paroxetine 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.	-9 / 94561	Nb of exposed children not reported. Overlapping with Colvin 2011, for which a similar result was obtained for Late intrauterine death (not reported here).
Costei (Controls unexposed, NOS), 2002	Canada 1996 - 1999	All pregnant women who called the Motherisk program.	Pregnant women exposed to paroxetine throughout the third trimester.	unexposed (general population or NOS) Pregnant women who used nonteratogenic drugs.	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.
Costei (Controls unexposed, sick), 2002	Canada 1996 - 1999	All pregnant women who called 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.	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.
Davis, 2007	USA 1996 - 2000	Female older than 15 years of age who were admitted to a hospital during study period for delivery of an infant and were continuously enrolled with prescription drug coverage for 1 year prior to the admission.	Fullterm infants exposed in utero to Paroxetine during first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Fullterm infants unexposed to Paroxetine.	182 / 49654	'Group Health Cooperative (Seattle, Washington), Harvard Pilgrim Health Care (Boston, Massachusetts), Henry Ford Health System (Detroit, Michigan), Kaiser Permanente Colorado (Denver, Colorado), and Kaiser Permanente Northwest (Portland, Oregon).'
Diav-Citrin, 2008	Israel, Italy and Germany 1994 - 2005	Women who contacted one of the three participating Teratology Information Services (TIS).	Pregnant women who contacted one TIS regarding exposures to Paroxetine.	unexposed (general population or NOS) Pregnant women who contacted one TIS regarding exposures known not to be teratogenic in similar time frames.	463 / 1467
Dubnov-Raz, 2008	Israel 2000 - 2005	All of the newborns born at a single tertiary care hospital.	Newborns exposed to Paroxetine in the immediate antepartum period. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Newborns born to healthy mothers who took no medications before delivery.	25 / 52
Einarson, 2008	Italy, Switzerland, Australia, Canada, Germany, Israel, USA and Finland Not specified.	Pregnant women who called Teratology information services to inquire about the use of a drug they are taking.	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.	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.
Einarson, 2009	Canada Not specified.	Women call the service for information regarding the safety of a drug.	Pregnant women who were exposed to Paroxetine 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.	148 / 928
Furu, 2015	Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2010	Women who gave birth to a live singleton infant during the study period (different periods according to country).	Infants born to women who filled a prescription for Paroxetine 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 LMP). (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Infants not exposed to any antidepressant (ATC code N06A) in utero.	2879 / 2266875
Heuvelman, 2023	United Kingdom 1995 - 2017	Pregnancies in Clinical Practice Research Datalink (CPRD) with a history of depressive symptoms or use of antidepressants in the preceding year before pregnancy.	Women who had initiated or continued Paroxetine for the treatment of depressive symptoms during pregnancy.	unexposed, sick Women who did not initiate or who discontinue antidepressants during pregnancy.	982 / 16330	Dose–response relationships, sibling design and negative control for antidepressants use as a whole (not for the class of antidepressants).
Huybrechts (Controls unexposed, NOS), 2014	USA 2000 - 2007	All completed pregnancies and their linked liveborn infants.	Pregnant women who have had exposure to Paroxetine 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.	11126 / 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).
Huybrechts (Controls unexposed, sick), 2014	USA 2000 - 2007	All completed pregnancies and their linked liveborn infants.	Pregnant women who have had exposure to Paroxetine 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.	8756 / 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).
Jimenez-Solem (Controls unexposed, NOS), 2012	Denmark 1997 - 2009	Pregnant women in Denmark and their offspring during the study period (all live births).	Pregnancies with a continuous exposure to Paroxetine 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.	568 / 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.
Jimenez-Solem (Controls unexposed, sick), 2012	Denmark 1997 - 2009	Pregnant women in Denmark and their offspring during the study period (all live births).	Pregnancies with a continuous exposure to Paroxetine, 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 expo- sure to an SSRI between 3 months before conception to 1 month after giving birth).	568 / 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.
Jordan, 2016	Norway, Wales and Denmark. 2000 - 2010	All foetuses (live or still born or termination of pregnancy) and infants who 1) would have appeared in the EUROCAT registries had they been diagnosed with a major congenital anomaly, 2) had linked maternal prescription data.	Prescription of Paroxetine 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.	1069 / 506155	Overlapping: The results of outcomes also reported in the largest study published by Wemakor 2015 (EUROCAT data in 12 countries; 1995-2009) are not reported here. Overlapping: Jordan 2016 included results of Knudsen 2014.
Kieler, 2012	Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2007	All singletons born after 231 gestational days (33 weeks).	A filled prescription of Paroxetine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) No filled prescription of selective serotonin reuptake inhibitors (SSRIs) during pregnancy.	3798 / 1588140
Kivistö, 2016	Finland 2002 - 2012	Women who gave birth at Kuopio University Hospital during the study period.	Pregnant women that used only Paroxetine during pregnancy.	unexposed (general population or NOS) Pregnant women not using any antidepressant medication.	32 / 24402	'Eleven women were excluded from the SSRI group due to combined therapy with an SSRI and an antidepressant belonging to another pharmacological group. '
Lee (Controls exposed to TCAs), 2025	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003 and December 31, 2018.	Women filling at least one prescription of Paroxetine 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.	77 / 613
Lee (Controls unexposed, general pop), 2025	China 2003 - 2018	All pregnant women aged 15–50 years who gave a singleton livebirth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003 and December 31, 2018.	Women filling at least one prescription of Paroxetine 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.	77 / 463440
Levinson-Castiel, 2006	Israel 2002 - 2004	Neonates born in the tertiary care center.	Neonates exposed to Paroxetine in utero during the entire pregnancy or at least during the third trimester. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Neonates not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero, born to healthy mothers.	37 / 60
Liu, 2017	Denmark 1998 - 2012	All liveborn singletons during the study period.	A prescription of Paroxetine 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).	1111 / 30079	Results for Psychiatric disorders (ICD-10 codes F00-F99) in the offspring (mean age at diagnosis: 8.5 years) not reported here because not only neurodevelopmental disorders but also psychiatric disorders.
Malm, 2011	Finland 1996 - 2006	All the Finnish births and terminations attributable to severe fetal anomalies during the study period.	Offspring of mothers with at least one purchase of Paroxetine 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.	968 / 618727	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.
Marks (Controls exposed to Bupropion), 2021	USA 2010 - 2019	Women who received at least one antidepressant prescription 3 months prior to conception through delivery.	Pregnant women with one (or more) prescription of Paroxetine 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.	55 / 406	'252 women (6.8%) prescribed >1 antidepressant'=> considered as monotherapy.
Marks (Controls unexposed, sick), 2021	USA 2010 - 2019	Women who received at least one antidepressant prescription 3 months prior to conception through delivery.	Pregnant women with one (or more) prescription of Paroxetine 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.	10 / -9	'252 women (6.8%) prescribed >1 antidepressant'=> considered as monotherapy. 'Neonatal intensive care unit admission" => not considered here because an exposure in early pregnancy could also lead to NICU admission.
Martin, 2024	Norway, Sweden and United Kingdom. 1996 - 2020	Singleton deliveries 22 weeks’ completed gestational weeks registered in the different databases during the study periods (UK: 1996-2018, Norway: 2009-2020, Sweden: 2006-2020).	Singleton deliveries with maternal Paroxetine (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.	2794 / 2408707	A group ‘multiple’ (i.e drug switching or concurrent prescriptions for different antidepressants) is available => thus individual antidepressant considered as monotherapy. Unexposed numbers: Table S4.
Maschi, 2008	Italy 1995 - 2003	Pregnant women who called the Drug and Health Information Centre at the ‘Mario Negri’ Institute.	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.	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.'
Merlob, 2009	Israel 2000 - 2007	Pregnant women who gave birth at the tertiary center	Pregnant women who reported using Paroxetine during 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 who not reported using Selective serotonin reuptake inhibitors (SSRIs).	92 / 67636	'Any infant with multiple congenital anomalies or dysmorphic features underwent genetic evaluation by a trained expert to exclude a congenital syndrome.'
Nijenhuis (Controls exposed to TCA), 2012	The Netherlands 1995 - 2009	Children selected by date of birth (between 1995 - 2009) and the female person (15–50 years) with the same address code (considered to be the mother).	Children of mothers exposed to Paroxetine 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 exposed to tricyclic antidepressants (TCAs) during pregnancy.	301 / 76	The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group.
Nijenhuis (Controls unexposed, NOS), 2012	The Netherlands 1995 - 2009	Children selected by date of birth (between 1995 - 2009) and the female person (15–50 years) with the same address code (considered to be the mother).	Children of mothers exposed to Paroxetine 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 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.	301 / 34908	The group exposed to both a SSRI and a TCA was excluded from the TCA exposed group and SSRI exposed group.
Nordeng (Controls unexposed, NOS), 2012	Norway 2000 - 2006	All women who gave birth in Norway, recruited into at the routine ultrasound examination in gestational weeks 17 to 18. Multiple births as well as infants with chromosomal abnormalities were excluded from the analyses.	Exposure to Paroxetine 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.	76 / 61648	Little overlapping between Nordeng 2012 (2000 - 2006) and Furu 2015 (including Norway 2005-10) => the 2 studies kept.
Nordeng (Controls unexposed, sick), 2012	Norway 2000 - 2006	All women who gave birth in Norway, recruited into at the routine ultrasound examination in gestational weeks 17 to 18. Multiple births as well as infants with chromosomal abnormalities were excluded from the analyses.	Exposure to Paroxetine 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.	76 / 1048	Little overlapping between Nordeng 2012 (2000 - 2006) and Furu 2015 (including Norway 2005-10) => the 2 studies kept.
Oberlander, 2008	Canada 1997 - 2002	About (92.7%) all live births (hospital and home births) in British Columbia during the study period.	Infants exposed to Paroxetine 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.	993 / 107320
Oberlander, 2004	Canada 1996 - 2000	Mothers and their infants studied during pregnancy as a part of a larger study of the effects of psychotropic medication use during and following pregnancy.	Infants prenatally exposed to Paroxetine alone. (This is a subgroup of exposure among the whole exposed group considered in the study).	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.	17 / 23
Ozturk, 2016	Turkey 2007 - 2012	Pregnant women referred to the prenatal consultation service for psychotropic drug exposure.	Pregnant women exposed to Paroxetine 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.	14 / 275	'Drug exposures took place in 81% during the first trimester, and 11% in all three trimesters. Medical treatments were discontinued in most of recognized pregnancies.'=> considered as 'At least first trimester'.
Palmsten (Controls exposed to TCA), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	Pregnant women with a depression diagnosis and a dispensation of Paroxetine 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.	3517 / 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.
Palmsten (Controls unexposed, sick), 2013	USA 2000 - 2007	Pregnant women with a depression diagnosis enrolled in Medicaid.	Pregnant women with a depression diagnosis and a dispensation of paroxetine 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 window.	3517 / 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.
Palmsten b, 2013	USA 2000 - 2007	Subcohort of pregnancies in women with diagnoses for mood or anxiety disorders (between one and five months before delivery), ending in live birth among women aged 12-55.	Women with a supply of Paroxetine 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.	2055 / 69044	Exclusion of women who were exposed to both drugs types (polytherapy) during the five months before delivery.
Rai (Controls exposed to TCA), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	Children of mothers who used Paroxetine 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).	264 / 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.
Rai (Controls unexposed, disease free), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	Children of mothers who used Paroxetine 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	264 / 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.
Rai (Controls unexposed, sick), 2017	Sweden 2001 - 2011	All young people aged 0 to 17 years, residing in Stockholm County between 2001 and 2011.	Children of mothers who used Paroxetine 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.	264 / 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.
Reis (Controls exposed to TCA), 2010	Sweden 1995 - 2007	Almost all deliveries in Sweden (1–2% missing).	Pregnant women who reported the use of Paroxetine in early pregnancy.	exposed to other treatment, sick Pregnant women who reported the use of tricyclic antidepressants (TCAs) in early pregnancy.	1208 / 1662
Reis (Controls unexposed, NOS), 2010	Sweden 1995 - 2007	Almost all deliveries in Sweden (1–2% missing).	Pregnant women who reported the use of Paroxetine in early pregnancy.	unexposed (general population or NOS) All other pregnant women in the register (not exposed to antidepressants during pregnancy).	1208 / 1062190	Overlapping: Kallen 2007 totally included in Reis 2010. Minor overlapping with Furu 2015 (including Sweden 2006-2010).
Stephansson, 2013	Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) 1996 - 2007	All singletons born after 154 gestational days during the study period.	One or more filled prescriptions for Paroxetine 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).	3745 / 1604649	Exclusion of pregnancies and births of mothers who had used other antidepressants with an effect on serotonin or norepinephrine activity (but not other antidepressants). Overlapping: Jimenez-Solem 2013 (not reported because included in Stephansson 2013).
Van der Veere, 2020	The Netherlands 2007 - 2010	Pregnant women, living in the vicinity of two Level-2 hospitals in the Northern part of the Netherlands were recruited via newspapers, midwifes, general practitioners, gynecologists, and psychiatrists.	Children who had been exposed to Paroxetine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Children who had not been exposed to psychotropic medication during pregnancy, with adjustment for maternal psychopathology.	27 / 41
Vial, 2006	France 1994 - 2005	Not specified.	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.	683 / -9
Viktorin (Controls unexposed, NOS), 2017	Sweden 2006 - 2014	All live-born children conceived from July 1, 2005 and born in 2006 and 2007.	Offspring that were born to mothers with at least 2 dispensations of Paroxetine 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.	173 / 172646
Viktorin (Controls unexposed, sick), 2017	Sweden 2006 - 2014	All live-born children conceived from July 1, 2005 and born in 2006 and 2007.	Offspring that were born to mothers with a history of depression or anxiety with at least 2 dispensations of Paroxetine overlapping the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Offspring that were born to mothers with a history of depression or anxiety without any dispensation of an antidepressant with a medication period overlapping the pregnancy.	108 / -9
Yaris, 2005	Turkey 1999 - 2004	Pregnant women calling for a counseling about the teratogenic risks of drugs, chemicals, and X-ray.	Women who were exposed to Paroxetine 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.	4 / 248	Multiple drug exposure. Raw data for Intrauterine exitus not reported because the nb of cases in the unexposed group not clearly stated.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Alwan, 2007	USA 1997 - 2002	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.	9622 / 4092	Overlapping: 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.'
Ames, 2021	USA 2003 - 2011	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.	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'.
Anderson, 2020	USA 1997 - 2011	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.	30630 / 11478	Overlapping: this study is an update of Alwan 2007, Werler 2018 (gastroschisis) and Lind 2013 (hypospadias). 'Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.'
Bakker, 2010	The Netherlands 1997 - 2006	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 )	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.
Chambers, 2006	USA and Canada 1998 - 2003	Mothers of subjects with Persistent pulmonary hypertension of the newborn (PPHN).	Mothers of subjects without Persistent pulmonary hypertension of the newborn (PPHN).	377 / 836
Dandjinou, 2019	Canada 1998 - 2015	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.	20905 / 209050	The 10 categories of exposure were mutually exclusive.
De Jonge, 2013	The Netherlands 1998 - 2008	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.	3212 / 29223	Overlapping with Wemakor 2015, a larger study based on 12 EUROCAT registries (included The Netherlands) for cardiac, respiratory and digestive malformations => thus these results not reported here.
De Vera, 2012	Canada 1997 - 2003	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.	1216 / 12160
Kerr, 2018	USA and Canada 1993 - 2015	Infants with microcephaly alone (“isolated”) and microcephaly that included other major birth defects (“non-isolated”),	Nonmalformed live-born infants.	166 / 12059	Authors analyzed separately “isolated” microcephaly and “non-isolated” microcephaly. Only isolated microcephaly are indexed in MetaPreg.
Kitchin, 2022	Spain 2002 - 2015	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.	18070 / 54209
Louik, 2007	USA and Canada 1993 - 2004	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.	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), metabolic disorders. No overlapping: Yazdy 2014 (2006-2011) - Louik 2007 (1993 - 2004)
Nakhai-Pour, 2010	Canada 1998 - 2003	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.	5124 / 51240
Wemakor, 2015	Belgium, Spain, Ireland, Malta, Netherlands, Norway, Denmark, FR, Germany, Italy, Switzerland, UK 1995 - 2009	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.	12876 / 17083	'Women were excluded if they took non-SSRI antidepressants or unspecified antidepressants and for the specific SSRI analyses, if they took more than one specific SSRI'. '12,876 with CHD, 13,024 with one or more of the 15 ‘signal’ subgroups'.
Yazdy, 2014	USA 2006 - 2011	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).	622 / 2002	No overlapping between Yazdy 2014 (2006 - 2011) and Louik 2007 (1993 - 2004).

master protocol