| Study | Country Study period |
Population source | Exposure definition | Non-exposure definition | Sample size | Rmk |
|---|---|---|---|---|---|---|
| Bellet - Aripiprazole, 2015 |
France 2004 - 2011 |
Pregnant women who had contacted a TIS (Teratology information service) centre, directly or via their health care provider. | Pregnant women exposed to aripiprazole during embryogenesis, i.e. 4 to 10 gestational weeks (GW, i.e. weeks after the last menstrual period). |
unexposed (general population or NOS)
Pregnant women without exposure or exposed to agents known to be non-teratogenic. |
86 / 172 | Patients were also excluded from the exposed group if they were co-exposed to known teratogen(s) during embryogenesis. |
| Boden - Olanzapine and/or clozapine, 2012 |
Sweden 2005 - 2009 |
All women (n = 358 203) with a singleton birth from July 1, 2005, through December 31, 2009. | Exposure was defined as filling a prescription for olanzapine and/or clozapine from last menstrual period to parturition. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Total population of pregnancies unexposed to antipsychotics. |
169 / 357696 | Olanzapine (n=159) and Clozapine (n=11). Overlapping with Heinonen 2022a for Gestational diabetes, SGA (weight birth), LGA (weight birth) and Kallen 2013 for preterm, 2 larger studies on atypical antipshychotics as a whole => Not reported here. |
| Bruno - Quetiapine, 2024 |
Denmark, Finland, Iceland, Norway, and Sweden 2000 - 2020 |
Pregnant women with a diagnosis of a psychiatric condition (ICD-10 codes: F10– F49, F60–F98, X60–X84, and Y10–Y34) in the 12 months before pregnancy start. | Pregnant women who filled ≥1 prescription for Quetiapine monotherapy (among antipsychotic medication) anytime between pregnancy start (based on the date of the first day of the last menstrual period) until the date of birth. |
unexposed, sick
Pregnant women who did not fill a prescription for any antipsychotic from 90 days before the start of pregnancy until birth. |
4492 / 197296 | Authors assessed several atypical antipsychotics (adjusted results), thus to avoid redundancy of controls, only one substance was reported in class meta-analysis (this one with the higher number of pregnancies). |
| Chan (Controls exposed to FGA), 2024 |
China 2003 - 2018 |
All pregnant women aged 15–50 years who gave a singleton live birth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003, and December 31, 2018. | Pregnant women filling at least one prescription of any second generation antipsychotic only (i.e no first generation antipsychotic) during the first trimester of pregnancy, which is defined as the first 90 days after the last menstrual period (LMP). |
exposed to other treatment, sick
Pregnant women filling at least one prescription of any first generation antipsychotic (only, i.e no second generation antipsychotic) during the first trimester of pregnancy, which is defined as the first 90 days after the last menstrual period (LMP). |
419 / 420 | Pregnancies with gestational age < 20 weeks, chromosomal abnormalities, fetal alcohol syndrome, abnormalities due to maternal infection, or exposure to known teratogens were excluded. |
| Chan (Controls unexposed, general pop), 2024 |
China 2003 - 2018 |
All pregnant women aged 15–50 years who gave a singleton live birth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003, and December 31, 2018. | Pregnant women filling at least one prescription of any second generation antipsychotic (only, i.e no first generation antipsychotic) during the first trimester of pregnancy, which is defined as the first 90 days after the last menstrual period (LMP). |
unexposed (general population or NOS)
Pregnant women who were not prescribed with any antipsychotic within the 90 days before the last menstrual period (LMP) and during the first trimester. |
419 / 464017 | Pregnancies with gestational age < 20 weeks, chromosomal abnormalities, fetal alcohol syndrome, abnormalities due to maternal infection, or exposure to known teratogens were excluded. |
| Chan (Controls unexposed, sick), 2024 |
China 2003 - 2018 |
All pregnant women aged 15–50 years who gave a singleton live birth or stillbirth (≥20 weeks of gestation) in public hospitals in Hong Kong between January 1, 2003, and December 31, 2018. | Pregnant women with psychiatric diagnosis filling at least one prescription of any second generation antipsychotic (only, i.e no first generation antipsychotic) during the first trimester of pregnancy, which is defined as the first 90 days after the last menstrual period (LMP). |
unexposed, sick
Pregnant women with psychiatric diagnosis who were not prescribed with any antipsychotic within the 90 days before the last menstrual period (LMP) and during the first trimester. |
363 / 6476 | Pregnancies with gestational age < 20 weeks, chromosomal abnormalities, fetal alcohol syndrome, abnormalities due to maternal infection, or exposure to known teratogens were excluded. |
| Cohen, 2022 |
USA 2008 - 2022 |
Any pregnant woman between the ages of 18 and 45 with a history of a psychiatric illness may enroll. | Pregnant women who have used at least one second-generation antipsychotics (SGAs) during pregnancy. |
exposed to other treatment, sick
Pregnant women with a history of psychiatric illness being treated with a variety of psychotropic medications other than second-generation antipsychotics. |
1031 / 1551 | Overlapping: Update of the study published by Cohen 2016 and Viguera 2021. Method based on the more detailed publication of the same registry (Viguera 2021). Cohen 2022 included data of Cohen 2023 and Viguera 2023a (on specific SGAs => not reported here). |
| Ellfolk (Control exposed to FGA), 2019 |
Finland 1996 - 2016 |
All pregnancies ending in singleton birth in Finland between 1 Jan. 1996 and 31 Dec. 2016 recorded in the Drugs and Pregnancy database. | Women who purchased second-generation antipsychotic (S-GAs: olanzapine, quetiapine, risperidone, aripiprazole, clozapine, ziprasidone, sertindole, or asenapine) at any time during pregnancy or 1 month before pregnancy. |
exposed to other treatment, sick
Women who purchased first-generation antipsychotic (F-GAs) at any time during pregnancy or 1 month before pregnancy but did not purchase S-GAs during the same period. |
4225 / 1576 | Data reported here: exposure to SGA during pregnancy (whatever the trimester). Authors also provided outcomes after SGA during at least two trimesters. Gestational hypertension/diabetes not reported because not sure that exposure occurred before outcome. |
| Ellfolk (Control unexposed), 2019 |
Finland 1996 - 2016 |
All pregnancies ending in singleton birth in Finland between 1 Jan. 1996 and 31 Dec. 2016 recorded in the Drugs and Pregnancy database. | Women who purchased second-generation antipsychotic (S-GAs: olanzapine, quetiapine, risperidone, aripiprazole, clozapine, ziprasidone, sertindole, or asenapine) at any time during pregnancy or 1 month before pregnancy. |
unexposed (general population or NOS)
Pregnant women who had no purchases of second-generation antipsychotic (S-GAs) or first-generation antipsychotic (F-GAs) during the period of 1 month prior to pregnancy until the end of pregnancy. |
4225 / 21125 | Gestational hypertension and diabetes not reported because not sure that exposure occurred before outcome. Data reported here: exposure to SGA during pregnancy (whatever trimester). Authors also provided outcomes after SGA during at least 2 trimesters. |
| Ellfolk (Controls exposed to FGA), 2021 |
Finland 1996 - 2017 |
Singleton pregnancies ending in livebirth, stillbirth or elective termination of pregnancy due to fetal malformation. | Pregnant women who purchased second-generation antipsychotic (S-GAs: olanzapine, quetiapine, risperidone, aripiprazole, clozapine, ziprasidone, sertindol, or asenapine) during 1 month before pregnancy until the end of first trimester. |
exposed to other treatment, sick
Pregnant women who purchased first-generation antipsychotic (F-GAs) during one month before pregnancy until the end of first trimester but did not purchase S-GAs during the same time period. |
3478 / 1030 | Overlapping: for Major, cardiac malformations and oral clefts: Ellfolk 2021 included in a larger study: Huybrechts 2023 (including Finland; 1996-2016) => outcomes not reported here. Stillbirths and gestational diabetes assessed in Ellfolk et al. 2019. |
| Ellfolk (Controls unexposed, NOS), 2021 |
Finland 1996 - 2017 |
Singleton pregnancies ending in livebirth, stillbirth or elective termination of pregnancy due to fetal malformation. | Pregnant women who purchased second-generation antipsychotic (S-GAs: olanzapine, quetiapine, risperidone, aripiprazole, clozapine, ziprasidone, sertindol, or asenapine) during 1 month before pregnancy until the end of first trimester. |
unexposed (general population or NOS)
Pregnant women who had no purchases of second-generation antipsychotic (S-GAs) or first-generation antipsychotic (F-GAs) during three months before pregnancy until end of first trimester. |
3478 / 22540 | Overlapping: for Major, cardiac malformations and oral clefts: Ellfolk 2021 included in a larger study: Huybrechts 2023 (including Finland; 1996-2016) => outcomes not reported here. Stillbirths and gestational diabetes assessed in Ellfolk et al. 2019. |
| Frayne (Control exposed to antidepressants), 2018 |
Australia 2007 - 2013 |
Women with severe mental illness who attended the Childbirth and Mental Illness antenatal clinic | Women receiving an atypical antipsychotic alone. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Women receiving antidepressants. (This is a subgroup of exposure among the whole exposed group considered in the study). |
75 / 50 | Gestational Diabetes Mellitus and preeclampsia not reported because no adequate control group (ceased early in the first trimester prior to their 12-week antenatal). |
| Frayne (Control unexposed, sick), 2018 |
Australia 2007 - 2013 |
Women with severe mental illness who attended the Childbirth and Mental Illness antenatal clinic | Women receiving an atypical antipsychotic alone. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Women receiving no medication (ceased their medication prior to conception, as part of a planned process, or ceased early in the first trimester prior to their 12-week antenatal review). (This is a subgroup of exposure among the whole exposed group considered in the study). |
75 / 58 | Gestational Diabetes Mellitus and preeclampsia not reported because no adequate control group (ceased early in the first trimester prior to their 12-week antenatal). |
| Habermann (Control exposed to FGA), 2013 |
Germany 1997 - 2009 |
Subjects were enrolled through the consultation process at Teratology Information Service (TIS Berlin). | Women exposed to at least 1 Second Generation Antipsycotics (SGA) during pregnancy; comedication with First Generation Antipsycotics (FGA) was allowed. |
exposed to other treatment, sick
Women exposed to First Generation Antipsychotics (FGAs) excluding comedication with Second Generation Antipsychotics (SGA) (cohort I). |
561 / 284 | Cases with potentially embryo- or fetotoxic drugs were not excluded for both the study cohort and the comparison cohort I but were assessed afterward. For the comparison cohort I, all available cases were included. |
| Habermann (Control unexposed, disease free), 2013 |
Germany 1997 - 2009 |
Subjects were enrolled through the consultation process at Teratology Information Service (TIS Berlin). | Pregnant women exposed to at least 1 Second Generation Antipsycotics (SGA) during pregnancy; comedication with First Generation Antipsycotics (FGA) was allowed. |
unexposed, disease free
Pregnant women using drugs known as not harmful to the unborn (comparison cohort II). Women exposed to teratogenic, fetotoxic, or insufficiently studied agents were excluded. |
561 / 1122 | Cases with potentially embryo- or fetotoxic drugs were not excluded for both the study cohort and the comparison cohort I but were assessed afterward. For the comparison cohort I, all available cases were included. |
| Halfdanarson (Controls exposed to FGA), 2022 |
5 nordic european countries: Denmark, Finland, Iceland, Norway, and Sweden. 1997 - 2017 |
All live-born singletons in the Medical Birth Registers of the 5 countries. | Children whose mothers filled at least one atypical antipsychotics (only) prescription during pregnancy (from LMP to birth). (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children whose mothers filled at least one typical antipsychotics (only) prescription during pregnancy (from LMP to birth). (This is a subgroup of exposure among the whole exposed group considered in the study). |
7752 / 6896 | Exclusion of children with missing or invalid data on gestational age and those with a chromosomal anomaly or fetal alcohol-spectrum disorder diagnosed in the first year of life. |
| Halfdanarson (Controls unexposed, NOS), 2022 |
5 nordic european countries: Denmark, Finland, Iceland, Norway, and Sweden. 1997 - 2017 |
All live-born singletons in the Medical Birth Registers of the 5 countries. | Children whose mothers filled at least one atypical antipsychotics prescription during pregnancy (from LMP to birth). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children whose mothers did not fill a prescription for an antipsychotic drug from 90 days before LMP to birth. |
7752 / 4308620 | Exclusion of children with missing or invalid data on gestational age and those with a chromosomal anomaly or fetal alcohol-spectrum disorder diagnosed in the first year of life. |
| Heinonen a (Controls unexposed, NOS), 2022 |
Sweden 2006 - 2017 |
All singleton births in Sweden registered in the Medical Birth Register (MBR) during the study period. | Pregnant women who used High metabolic risk second-generation antipsychotic drugs (S-GAs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
All pregnant women during the study period who have not used antipsychotics during pregnancy, including those from the other control group “antipsychotics before or after but not during pregnancy”. |
1710 / 1296539 | Results of High metabolic risk S-GAs (HR S-GAs) are included here: quetiapine (n = 1026), olanzapine (n = 771) and clozapine (n = 29). Gestational diabetes not reported because not sure that exposure occurred before outcome (authors' confirmation). |
| Heinonen a (Controls unexposed, sick), 2022 |
Sweden 2006 - 2017 |
All singleton births in Sweden registered in the Medical Birth Register (MBR) during the study period. | Pregnant women who used High metabolic risk second-generation antipsychotic drugs (S-GAs) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women who used antipsychotics before or after but not during the actual pregnancy. |
1710 / 34492 | Results of High metabolic risk S-GAs (HR S-GAs) are included here: quetiapine (n = 1026), olanzapine (n = 771) and clozapine (n = 29). Gestational diabetes not reported here because not sure that exposure occurred before outcome (authors' confirmation). |
| Heinonen b (Controls exposed to FGA), 2022 |
Sweden 2006 - 2017 |
All singleton births in Sweden ( >97% of all births) during the study period. | Infants exposed to second generation antipsychotics during pregnancy (early or late). |
exposed to other treatment, sick
Infants exposed to first generation antipsychotics during pregnancy (early or late). |
-9 / -9 | The most prescribed antipsychotics in the pregnant population during the study period were quetiapine (1021 exposures), olanzapine (771 exposures) and aripiprazole (334 exposures), all second-generation antipsychotics. |
| Heinonen b (Controls unexposed, NOS), 2022 |
Sweden 2006 - 2017 |
All singleton births in Sweden ( >97% of all births) during the study period. | Infants exposed to second generation antipsychotics during pregnancy (early or late). |
unexposed (general population or NOS)
Infants born of mothers not treated with antipsychotics during the entire study period. |
-9 / 1262047 | The most prescribed antipsychotics in the pregnant population during the study period were quetiapine (1021 exposures), olanzapine (771 exposures) and aripiprazole (334 exposures), all second-generation antipsychotics. |
| Heinonen b (Controls unexposed, sick), 2022 |
Sweden 2006 - 2017 |
All singleton births in Sweden ( >97% of all births) during the study period. | Infants exposed to second generation antipsychotics during pregnancy (early or late). |
unexposed, sick
Infants born of mothers treated with antipsychotics before or after but not during the pregnancy. |
-9 / 34492 | The most prescribed antipsychotics in the pregnant population during the study period were quetiapine (1021 exposures), olanzapine (771 exposures) and aripiprazole (334 exposures), all second-generation antipsychotics. |
| Hironaka (Control exposed to BZD), 2011 |
Japan 2005 - 2009 |
Female patients who delivered at Nagoya University Hospital. | Women with mental disorders (but without any other complications) taking atypical antipsychotics. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Women with mental disorders (but without any other complications) taking benzodiazepines. (This is a subgroup of exposure among the whole exposed group considered in the study). |
9 / 5 | Gestational diabete, preeclampsia, low birth weight: not reported because neither case in exposed group nor in unexposed group |
| Hironaka (Control unexposed, disease free), 2011 |
Japan 2005 - 2009 |
Female patients who delivered at Nagoya University Hospital. | Women with mental disorders (but without any other complications) taking atypical antipsychotics. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Women without mental disorders. |
9 / 278 | |
| Hironaka (Control unexposed, sick), 2011 |
Japan 2005 - 2009 |
Female patients who delivered at Nagoya University Hospital. | Women with schizophrenia (but without any other complications) taking atypical antipsychotics. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Women with schizophrenia without medication during pregnancy. |
9 / 3 | |
| Huybrechts (Controls unexposed, NOS), 2023 |
Denmark, Finland, Iceland, Norway, Sweden and USA. 1996 - 2018 |
All pregnancies resulting in singleton live-born infants (for Nordic cohorts) and publicly insured mothers linked to their live-born infants (for USA). | Pregnancies with 1 or more prescriptions of the atypical antipsychotics during the first trimester, the period for organogenesis. |
unexposed (general population or NOS)
Pregnancies who did not fill any antipsychotic prescriptions during the 3 months prior to pregnancy until the end of the first trimester. |
21751 / 6455324 | Overlapping: Data of Huybrechts 2016, Liu 2023 and Ellfolk 2021 totally and partially (major, cardiac, oral clefts) included in this larger study. Data of Reis 2008 (Sweden; 1995-2005) not included in Huybrechts 2023 (Sweden: 2006-2016). |
| Huybrechts (Controls unexposed, sick), 2023 |
Denmark, Finland, Iceland, Norway, Sweden and USA. 1996 - 2018 |
All pregnancies resulting in singleton live-born infants (for Nordic cohorts) and publicly insured mothers linked to their live-born infants (for USA). | Pregnancies with 1 or more prescriptions of the atypical antipsychotics during the first trimester, the period for organogenesis. |
unexposed, sick
Pregnancies in women with mental health condition, who did not fill any antipsychotic prescriptions during the 3 months prior to pregnancy until the end of the first trimester. |
17068 / 318731 | Overlapping: Data of Huybrechts 2016, Liu 2023 and Ellfolk 2021 totally and partially (major, cardiac, oral clefts) included in this larger study. Data of Reis 2008 (Sweden; 1995-2005) not included in Huybrechts 2023 (Sweden: 2006-2016). |
| Källen, 2013 |
Sweden 1996 - 2011 |
Nearly all births in Sweden and is based on standardized medical records, used in the whole country. | Pregnant women exposed to second generation antipsychotics. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Not specified. |
258 / -9 | The study was related to the Central Nervous System (CNS) active drugs. RR calculated with observed/expected numbers. All outcomes are provided for neuroleptics as a whole excepted for preterm (2nd generation antipsychotics). |
| Kananen - Quetiapine, 2023 |
Finland 2002 - 2016 |
Women who gave birth (at gestational week ≥22 or birth weight ≥500g) at Kuopio University Hospital between 2002 and 2016. | All pregnant women who either self-reported the use or were administered quetiapine at the Kuopio University Hospital (KUH). |
unexposed (general population or NOS)
All pregnant women without antipsychotic exposure. |
153 / 35837 | OR based on 152 and 35133 exposed and unexposed pregnancy, respectively (values excluding multifetal gestations and antiemetics users). Quetiapine with other antipsychotic agent: 3.7%. |
| Kernizan, 2019 |
USA 2014 - 2017 |
Pregnant patients with bipolar disorder, with two documented visits during the study period and a SSM health-system delivery. | Pregnant women exposed to Lurasidone and 'other atypical antipsychotics' during pregnancy. |
unexposed, sick
Pregnant women not exposed to mood stabilizer during pregnancy. |
45 / 140 | For preterm and malfo: Overlapping Kernizan 2019 and 2024: use of Kernizan 2024 because full text publication (Abstract in 2019) => outcomes not reported here. |
| Kernizan (Controls exposed to LTG), 2024 |
USA 2014 - 2017 |
Mothers and neonates who were born to pregnant women who were at least 14 years of age with a diagnosis of bipolar disorder and had at least two prenatal care visits at the Maternal and Fetal Care Center at SSM Health St. Mary's Hospital. | Pregnant women with a diagnosis of bipolar disorder who were prescribed atypical antipsychotic only (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) at some point of their pregnancy. |
exposed to other treatment, sick
Pregnant women with a diagnosis of bipolar disorder who were prescribed lamotrigine only at some point of their pregnancy. |
46 / 13 | Addition of Lurasidone and 'other atypical antipsychotics' (authors provided data of women exposed to a single mood stabilizer and no adjustment). |
| Kernizan (Controls unexposed, sick), 2024 |
USA 2014 - 2017 |
Mothers and neonates who were born to pregnant women who were at least 14 years of age with a diagnosis of bipolar disorder and had at least two prenatal care visits at the Maternal and Fetal Care Center at SSM Health St. Mary's Hospital. | Pregnant women with a diagnosis of bipolar disorder who were prescribed atypical antipsychotic only (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) at some point of their pregnancy. |
unexposed, sick
Pregnant women with a diagnosis of bipolar disorder who were not prescribed mood stabilizers (lithium, antiepileptics, atypical antipsychotics) at some point of their pregnancy. |
46 / 139 | Addition of Lurasidone and 'other atypical antipsychotics' (authors provided data of women exposed to a single mood stabilizer and no adjustment). |
| Kulkarni - Quetiapine, 2024 |
Australia 2005 - 2019 |
Women who were pregnant or had a baby in the last 12 months, taking antipsychotic medication during pregnancy, and living in Australia. | Women who had a diagnosis of a schizophrenia spectrum disorder and took quetiapine during the first trimester of pregnancy (at minimum). |
unexposed, sick
Women with a diagnosis of schizophrenia spectrum disorder who chose not to take any antipsychotic during the first trimester of pregnancy (at a minimum). |
53 / 24 | Authors studied 2 atypical antipsychotics => To avoid redundancy of controls only one is used in the class meta-analysis, this one with the highest number of exposed pregnancies. |
| Lin (Control exposed to FGA), 2010 |
Taiwan 2001 - 2003 |
Mothers with schizophrenia having singleton live births between January 1, 2001, and December 31, 2003 identified by the National Health Insurance Research Database. | Mothers with schizophrenia who had been prescribed a monotherapy of atypical antipsychotics for more than 30 days while pregnant. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Mothers with schizophrenia who had been prescribed a monotherapy of typical antipsychotics for more than 30 days while pregnant. (This is a subgroup of exposure among the whole exposed group considered in the study). |
48 / 194 | |
| Lin (Control unexposed, disease free), 2010 |
Taiwan 2001 - 2003 |
Mothers with schizophrenia having singleton live births between January 1, 2001, and December 31, 2003 identified by the National Health Insurance Research Database. | Mothers with schizophrenia who had been prescribed a monotherapy of atypical antipsychotics for more than 30 days while pregnant. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Extraction from the remaining mothers in the database, excluding mothers who had once been diagnosed with any type of mental disorder (ICD-9-CM codes 290–319) or chronic diseases (such as lupus erythematosis, rheumatoid arthritis, gout, sarcoidosis, or ankylosing spondylitis) between 1996 and 2003. |
48 / 3480 | |
| Lin (Control unexposed, sick), 2010 |
Taiwan 2001 - 2003 |
Mothers with schizophrenia having singleton live births between January 1, 2001, and December 31, 2003 identified by the National Health Insurance Research Database. | Mothers with schizophrenia who had been prescribed a monotherapy of atypical antipsychotics for more than 30 days while pregnant. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Women with schizophrenia without antipsychotics during pregnancy. |
48 / 454 | To assess impact of illness, women without schizophrenia were also compared to women with schizophrenia without antispychotics during pregnancy. |
| McKenna, 2005 |
Canada, Israel and England Not specified |
Women who contacted the line for information about agent taking during pregnancy.. | Women who has taken an atypical antipsychotic within 3 months of pregnancy or during pregnancy. |
unexposed, disease free
Subsequent woman who contacted the service regarding exposure to a non-teratogenic agent. Women who reported a psychiatric diagnosis or psychotropic medication use were excluded from the comparison group. |
151 / 151 | All of the women were exposed in the first trimester. They included women exposed to olanzapine (N = 60), risperidone (N = 49), quetiapine (N = 36), and clozapine (N = 6). |
| Newham (Control exposed to FGA), 2008 |
United Kingdom 1995 - 2006 |
Babies born after full-term (37 weeks gestation) deliveries to mothers called the TIS and exposed to antipsychotics in therapeutic doses or one of the reference medications | Pregnant women exposed to atypical antipsychotic drugs. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women exposed to typical antipsychotic drugs. (This is a subgroup of exposure among the whole exposed group considered in the study). |
25 / 45 | 45 (53% males) were exposed to typical antipsychotics (10 monotherapy antipsychotic) and 25 (24% males) to atypical antipsychotics (10 monotherapy antipsychotic) |
| Newham (Control unexposed, disease free), 2008 |
United Kingdom 1995 - 2006 |
Babies born after full-term (37 weeks gestation) deliveries to mothers called the TIS and exposed to antipsychotics in therapeutic doses or one of the reference medications | Pregnant women exposed to atypical antipsychotic drugs. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnant women exposed to monotherapy of drugs considered to be non-teratogenic and with no associated foetal or adult weight side-effects (list compiled by the NTIS: predominantly antihistamines, antibiotics, laxatives, b2-agonist inhalants, astringents, proton pump inhibitors and antimalarials). |
25 / 38 | 45 (53% males) were exposed to typical antipsychotics (10 monotherapy antipsychotic) and 25 (24% males) to atypical antipsychotics (10 monotherapy antipsychotic). |
| Newport, 2007 |
USA Not specified |
Pregnant women treated with antipsychotics recruited from the Emory Women’s Mental Health Program. | Pregnant women receiving receiving a stable daily dose of an antipsychotic for >5 elimination half-lives at delivery. Addition of exposure to Olanzapine, Quetiapine and Risperidone. |
exposed to other treatment, sick
Pregnant women receiving Haloperidol. |
41 / 13 | Each substance is a subanalyse. For the meta-analysis, we considered Atypic antipsychotics as the exposed group and Haloperidol as the control group. In the original publication, the authors provided outcomes for each substance. |
| Ozturk, 2016 |
Turkey 2007 - 2012 |
Women referred to our prenatal consultation service for psychotropic drug exposure. | Pregnancies exposed to atypical antipsychotropic (addition of Quetiapine, Risperidone and Olanzapine). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnancies not exposed to known teratogens, in the same year applying the same procedure for data collection and follow-up. |
15 / 275 | Authors investigated Psychotropic drugs as a whole but also provided data for individual substances. Drug exposures took place in 81% during the first trimester, and 11% in all three trimesters. Distinction between miscarriage and stillbirth. |
| Panchaud, 2017 |
USA 2008 - 2016 |
Any pregnant woman between the ages of 18 and 45 with a history of a psychiatric illness may enroll. | The exposed group consists of women who have used one or more second-generation antipsychotics during pregnancy. |
exposed to other treatment, sick
The comparison group consists mostly of women with a history of psychiatric illness being treated with a variety of psychotropic medications other than second-generation antipsychotics. |
303 / 149 | Study with the same protocol that Cohen 2016 and 2018 but related to an other outcome. '303 with first-trimester exposure to an SGA and a comparison group of 149 who remained unexposed to an SGA throughout pregnancy ' |
| Park, 2018 |
USA 2000 - 2010 |
Women who during the 3 months before their last menstrual period filled a prescription for one of the five most frequently used atypical antipsychotics: aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. | Pregnant women who had two or more prescriptions dispensed during the first 140 days of their pregnancy for the same antipsychotic medication (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) that they received before pregnancy. Exclusion if more than 1 studied antipsychotic. |
unexposed, sick
Pregnant women who had no prescriptions dispensed for an antipsychotic medication during the first 140 days of pregnancy were classified as “discontinuers.” |
2872 / 7507 | Primary analyses performed individually for each substance (not for atypic antipsychotic as a whole), but authors provide raw data and analysis for each substance. RR reported here is the pooled aOR (by meta-analysis) of each substances. |
| Paulus, 2005 |
Germany The last 15 years |
Pregnant women for which physicians and patients contacted the TIS. | Pregnant women exposed to atypical antipsychotics in the first trimester for which the TIS was contacted. |
unexposed, disease free
Pregnant women which was not or not severely exposed for which the TIS was contacted, in the same interval. |
95 / 578 | This study (clozapine: n=36, risperidone: n=18, olanzapine: n=35, quetiapine: n=6) did not incorporate data published by Paulus 2013 (aripiprazole: n=68). |
| Paulus - Aripiprazole only, 2013 |
Germany 2005 - 2012 |
Pregnant women for which physicians and patients contacted the TIS. | Pregnant women exposed to Aripiprazole in the first trimester for which the TIS was contacted. |
unexposed (general population or NOS)
Pregnant women not exposed to aripiprazole or exposed to non-teratogenic agents for which the TIS was contacted, in the same interval. |
68 / 194 | Study only related to Aripiprazole. This study (aripiprazole: n=68) did not incorporate data published by Paulus 2005 (clozapine: n=36, risperidone: n=18, olanzapine: n=35, quetiapine: n=6). |
| Peng, 2013 |
China 2007 - 2010 |
Women with singleton pregnancy at more than 38 weeks who were seeking prenatal care in the department of the Second Xiangya Hospital. | Women with a diagnosis of schizophrenia who were taking a targeted antipsychotic agent including clozapine, olanzapine, risperidone, sulpiride or quetiapine throughout the pregnancy. |
unexposed, disease free
Women who not have any mental disorder and were not treated with any antipsychotics in the same department. |
76 / 76 | Continuous variables: there were no significant differences between the two groups in the Apgar score at 1 and 5 min, as well as the mean weight, height, and brain circumference. |
| Petersen (Control discontinued treatment before pregnancy), 2016 |
United Kingdom 1995 - 2012 |
Pregnant women registered in the 2 electronic health records data (i.e around 10% of the United Kingdom population). | Women with records of atypical antipsychotic treatments two years before start of pregnancy and with records issued between 31 and 105 days (inclusive) after the start of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Women with records of atypical antipsychotic treatment in the two years before start of pregnancy, but no prescriptions issued after four weeks prior to pregnancy start. |
280 / 302 | Atypical antipsychotics are a subgroup of the entire analysis. |
| Petersen (Control exposed to FGA), 2016 |
United Kingdom 1995 - 2002 |
Pregnant women registered in the 2 electronic health records data (i.e around 10% of the United Kingdom population). | Women with records of atypical antipsychotic treatments two years before start of pregnancy and with records issued between 31 and 105 days (inclusive) after the start of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Women with records of typical antipsychotic treatments two years before start of pregnancy and with records issued between 31 and 105 days (inclusive) after the start of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
280 / 157 | |
| Petersen (Control unexposed, disease free), 2016 |
United Kingdom 1995 - 2002 |
Pregnant women registered in the 2 electronic health records data (i.e around 10% of the United Kingdom population). | Women with records of atypical antipsychotic treatments two years before start of pregnancy and with records issued between 31 and 105 days (inclusive) after the start of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnant women with no records of atypical antipsychotic treatment in the two years before the start of pregnancy and through to the delivery date. |
280 / 318434 | Atypical antipsychotics are a subgroup of the entire analysis. |
| Raguideau, 2017 |
France 2011 - 2015 |
All pregnancies ending between 2011 and 2015, regardless of the outcome (live birth, stillbirth or therapeutic abortions after 22 WA), were eligible for inclusion. | Pregnancies exposed to atypical antipsychotics during the two first months of pregnancy (reimbursement occurring the month before the pregnancy or during the two first months of pregnancy). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Pregnancies not exposed to bipolar disorder drugs during the two first months of pregnancy (reimbursement occurring the month before the pregnancy or during the two first months of pregnancy). |
2286 / 1888130 | The study not considered all major malformations but 26 malfo. Authors did not analyse atypic antipsychotic as a subgroup, but provide raw data for each substance. Results included are the sum of outcomes for each substance (in monotherapy). |
| Reis (Control exposed to FGA), 2008 |
Sweden 1995 - 2005 |
Whole country (1.4% of all deliveries in Sweden are missing in the register). | Women who had reported the use of 'Any second-generation antipsychotic' in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Women who had reported the use of 'Any first-generation antipsychotic' in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
147 / 435 | Atypical and typical antipsychotics are subgroups of the entire study. Atypical versus Typical. OR and adjustement performed for other groups. Relative severe malformations, with exclusion of known chromosome anomalies. |
| Reis (Control unexposed, NOS), 2008 |
Sweden 1995 - 2005 |
Whole country (1.4% of all deliveries in Sweden are missing in the register). | Women who had reported the use of 'Any second-generation antipsychotic' in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
All other women in the register. |
147 / 958729 | Atypical antipsychotics are a subgroup of the entire study. OR and adjustment performed for other groups. Relative severe malformations, with exclusion of known chromosome anomalies. |
| Sadowski, 2013 |
Canada 2005 - 2009 |
Women who directly contacted the Motherisk Program at the Hospital for Sick Children in Toronto, Canada. | Women who confirmed the use of Second-generation antipsychotics (SGAs) for a minimum of 4 weeks of pregnancy. |
unexposed, disease free
Women who reported exposure to non-teratogenic agents (eg, acetaminophen, antihistamines, etc). Control women who reported a history of psychiatric disorders or who were exposed in their current pregnancy to a known teratogen were excluded. |
133 / 133 | Gestational diabetes and hypertension not reported because not sure that exposure occurred before outcome. |
| Schaffer (Controls unexposed, NOS), 2019 |
Australia 2005 - 2012 |
All women who gave birth from 1 January 2005 to 31 December 2012, but analysis restricted to restricted the analysis to women who were concessional beneficiaries and who had at least one dispensing for any medicine. | All pregnant women where the estimated duration of use of any atypical antipsychotic overlapped with the study period. Sum of all groups exposed during pregnancy (3: Long-term use, low daily dose; 4: Use in pregnancy only; 5: Long-term use, moderate daily dose; 6: Long-term, high daily dose). |
unexposed (general population or NOS)
All other pregnant women were considered ‘unexposed’ (to any antipsychotics). |
1322 / 135252 | Antipsychotic exposures consisted of > 90% atypical antipsychotics (1214/1322) => considered as atypical antipsychotic exposures. |
| Schaffer (Controls unexposed, sick), 2019 |
Australia 2005 - 2012 |
All women who gave birth from 1 January 2005 to 31 December 2012, but analysis restricted to restricted the analysis to women who were concessional beneficiaries and who had at least one dispensing for any medicine. | All pregnant women where the estimated duration of use of any atypical antipsychotic overlapped with the study period. Sum of all groups exposed during pregnancy (3: Long-term use, low daily dose; 4: Use in pregnancy only; 5: Long-term use, moderate daily dose; 6: Long-term, high daily dose). |
unexposed, sick
Pregnant women who had short-term use of antipsychotics with use commencing and ending well before pregnancy or with with use immediately preceding pregnancy. Sum of the 2 groups of exposure before pregnancy (1: Short-term use well before pregnancy and 2: Short-term use preceding pregnancy). |
1322 / 1419 | Antipsychotic exposures consisted of > 90% atypical antipsychotics (1214/1322) => considered as atypical antipsychotic exposures. Exclusion of lithium (N05AN01) and prochlorperazine. |
| Sorensen - Olanzapine, 2015 |
Denmark 1997 - 2008 |
Pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). | Any prescription of Olanzapine redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. (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 redeem any prescription of antipsychotic medications during the exposure window. |
223 / 841183 | Authors assessed several antipsychotics (but not atypic antipsychotic as a subgroup), thus to avoid redundancy of controls, only one was reported here => this one with the higher number of exposures. |
| Straub, 2022 |
USA 2000 - 2015 |
Mothers (12-55 years old) who were continuously insured from 3 months before until 1 month after pregnancy. | Children whose mother filled a prescription for any atypical antipsychotic medication during the second half of pregnancy (>18 gestational weeks). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children born to mothers with no antipsychotic dispensing from 90 days before pregnancy until birth. |
9390 / 3309095 | Estimates from both cohorts were combined through meta-analysis by authors. Children with a known chromosomal or genetic abnormality were excluded. |
| Sutter-Dallay, 2015 |
France 2001 - 2010 |
Women (> 18 years) with postpartum psychiatric disorders hospitalized for at least 5 consecutive days, jointly admitted with their child (< 1 year) in Mother-Baby Units. | Women used at least 1 Second generation antipsychotic (SGAs: amisulpride, risperidone, olanzapine, aripiprazole, and clozapine) during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Mothers without psychotropic drug use during pregnancy. |
55 / 640 | Subgroup Atypical antipsychotics NOT provided for all outcomes. The following categories were investigated: antipsychotics (FGA, SGA), antidepressants (SSRI and SNRI, others), mood stabilizers (lithium, anticonvulsivants) and anxiolytics/hypnotics. |
| Swetlik, 2024 |
|
-
|
-9 / -9 | Only the result is extracted for potential retrieval at a later stage, as the outcome is not currently considered in metaPreg (results of Ages and stages questionnaire not reported because to few questions in this questionnaire). | ||
| Vial (Control exposed to FGA), 2009 |
France 1997 - 2007 |
Pregnant women who had contacted the TIS centre to request a risk evaluation | Pregnant women exposed to risperidone and/or olanzapine during the during embryogenesis for a psychiatric indication. |
exposed to other treatment, sick
Pregnant women exposed to conventional antipsychotics (chlorpromazine, cyamemazine and haloperidol) the during embryogenesis for a psychiatric indication. |
89 / 143 | Data were extracted from the 2 abstracts (Vial 2009 and Garayt 2009). Exposure during embryogenesis (i.e.4 to 10weeks after the last menstrual period). Exposure: olanzapine (n = 62), risperidone (n = 26) or to both drugs successively (n = 1). |
| Vial (Control unexposed, NOS), 2009 |
France 1997 - 2007 |
Pregnant women who had contacted the TIS centre to request a risk evaluation. | Pregnant women exposed to risperidone and/or olanzapine the during embryogenesis for a psychiatric indication |
unexposed (general population or NOS)
Pregnant women not exposed to antipsychotics and teratogenic agents. |
89 / 178 | Data were extracted from the 2 abstracts (Vial 2009 and Garayt 2009). Exposure during embryogenesis (i.e.4 to 10weeks after the last menstrual period). Exposure: olanzapine (n = 62), risperidone (n = 26) or to both drugs successively (n = 1). |
| Vigod, 2015 |
Canada 2003 - 2012 |
All women who delivered a singleton infant (live birth or stillbirth) in Ontario during the study period registered in health administrative databases housed at the Institute for Clinical Evaluative Sciences (ICES) in Toronto. | At least two consecutive prescriptions for any antipsychotics (about 90% of atypical antipsychotics) of filled between the conception date and the delivery date. At least one prescriptions filled prior to 27 GW. |
unexposed, sick
Matched women not exposed to any antipsychotic drug during pregnancy using a HDPS matching algorithm to minimise treatment selection bias (leading to similar psychiatric diagnoses before index pregnancy => considered as 'unexposed, sick'). |
1021 / 1021 | For atypical antipsy: adjusted RR only provided on a graph (not used for the meta-analysis). We used the RRa provided for antipsychotics because about 90% were exclusively prescribed an atypical antipsychotics. |
| Viguera b, 2023 |
USA 2008 - 2020 |
Pregnant women between the ages of 18 and 45 years with histories of psychiatric disorders | Infants exposed to a Second-generation antipsychotic (SGA) during pregnancy, without the use of any Selective serotonin reuptake inhibitors (SSRIs) or Serotonin-norepinephrine reuptake inhibitors (SNRIs) but with exposure to other psychotropics. |
exposed to other treatment, sick
Infants exposed to a Selective serotonin reuptake inhibitors (SSRIs) and/or Serotonin-norepinephrine reuptake inhibitors (SNRIs), without any exposure to Second-generation antipsychotics (SGAs) but with exposure to other psychotropics. |
193 / 191 | The majority of women in each group used these medications across the entire course of their pregnancy, including the third trimester. Other psychotropics included lithium, anticonvulsants, stimulants, benzodiazepines, and hypnotics. |
| Wang a (Controls exposed to FGA), 2021 |
Hong Kong 2001 - 2019 |
All pregnant episodes of females aged 15 to 50 years old who delivered a live birth during the study period. | Infants whose mother received any second-generation antipsychotics (only SGAs) during the pregnancy period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants whose mother received any first-generation antipsychotics (only FGAs) during the pregnancy period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
199 / 405 | The pregnancy episodes with maternal exposure to antidepressants or lithium during pregnancy were removed. |
| Wang a (Controls unexposed, NOS), 2021 |
Hong Kong 2001 - 2019 |
All pregnant episodes of females aged 15 to 50 years old who delivered a live birth during the study period. | Infants whose mother received any second-generation antipsychotics (SGAs) during the pregnancy period. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Infants whose mother did not use antipsychotics during pregnancy. |
199 / 410545 | The pregnancy episodes with maternal exposure to antidepressants or lithium during pregnancy were removed. |
| Wang b - HK cohort, 2021 |
China 2001 - 2015 |
Primiparous pregnancies resulting in a live or stillbirth among the entire pregnancy population of the Clinical Data Analysis and Reporting System (CDARS; representing 165 hospitals/institutions) aged between 15 and 50 years old during the study period. | Pregnant women who received at least 56 days coverage time of prescriptions of Second generation antipsychotics before and during pregnancy (continuers). |
unexposed, sick
Pregnant women who did not receive any antipsychotic during pregnancy, but did before pregnancy (discontinuers). |
149 / 340 | The most commonly used antipsychotic agents in CDARS were haloperidol (n = 443), risperidone (n = 353) and trifluoperazine (n = 317). |
| Wang b - UK cohort, 2021 |
United Kingdom 1990 - 2017 |
Primiparous pregnancies resulting in a live or stillbirth among the entire pregnancy population of the Health Improvement Network (THIN; representing over 6% of the UK population) aged between 15 and 50 years old during the study period. | Pregnant women who received at least two prescriptions (normally 28 days for one prescription) of Second generation antipsychotics before and during pregnancy (continuers). |
unexposed, sick
Pregnant women who did not receive any antipsychotic during pregnancy, but did before pregnancy (discontinuers). |
349 / 1577 | The most commonly used antipsychotic agents in THIN were quetiapine (n = 571), chlorpromazine (n = 450) and olanzapine (n = 450). |
| Wurtz, 2017 |
Denmark 1997 - 2012 |
All singleton live-born children in Denmark from January 1, 1997 to December 31, 2012. | Any prescription of the second-generation Antipsychotics registered during the exposure window (defined as 30 days before the estimated first day of the last menstrual period to the day before birth). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
No prescription of antipsychotic medication registered in the Danish Register of Medicinal Product Statistics during the exposure window (defined as 30 days before the estimated first day of the last menstrual period to the day before birth). |
-9 / 960527 | The exposure of interest was the mother’s use of Antipsychotic (AP) during pregnancy. Second generation antipsychotic, quetiapine and olanzapine are subanalyses (the number of exposed pregnancies were not reported). |
| Yakuwa, 2019 |
Japan 2005 - 2016 |
Pregnant women was contacted the Japan Drug Information Institute in Pregnancy during the study period. | Pregnant women who had been exposed to second-generation antipsychotics (SGAs) in first-trimester. |
unexposed (general population or NOS)
Pregnant women who had not been exposed to second-generation antipsychotics (SGAs) and teratogenic drugs. |
404 / 4330 | Exposures: aripiprazole (N=147), quetiapine (N=91), olanzapine (N=83), risperidone (N=71), perospirone (N=32), blonanserin (N=24), and paliperidone (N=2). |
| 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 atypical antipsychotropic drugs 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. |
| Yeh, 2021 |
Taiwan 2002 - 2011 |
Pregnant women with bipolar disorder who were pregnant and gave birth to a child during the study period. | Pregnant women with bipolar disorder receiving Atypical Antipsychotics (aripiprazole, risperidone, paliperidone, olanzapine, amisulpride, ziprasidone, clozapine, and quetiapine) 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. |
45 / 5243 |
| Study | Country Study period |
Case | Control | Sample size | Rmk |
|---|---|---|---|---|---|
| Anderson, 2020 |
USA 1997 - 2011 |
Infants with at least one of 30 major structural birth defects with unknown etiologies studied (among live births (all sites), stillbirths (all sites except NY before 2000 and NJ), and terminations (all sites except GA before 1999, MA before 2011, NY before 2000, and NJ)). | Liveborn infants without major birth defects who were randomly sampled from the same geographic location and study years as birth defect cases using data from hospital birth logs or vital records. | 22387 / 11470 | Infants with recognized single-gene disorders or chromosomal abnormalities were excluded. Exposure to quetiapine, aripiprazole, olanzapine and risperidone. |
| Ishikawa, 2024 |
Japan 2005 - 2022 |
Women whose pregnancies ended in a miscarriage that occurred between the beginning of the fourth and 22nd weeks of gestation. | Women randomly selected from the entire cohort of pregnancies by risk-set sampling with replacement and were individually matched to the cases (3:1). | 44118 / 132317 |
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