Olanzapine

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Boden (Control exposed to other antipsyhcotics), 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).	exposed to other treatment, sick Exposure was defined as filling a prescription for other antipsychotics from last menstrual period to parturition. (This is a subgroup of exposure among the whole exposed group considered in the study).	169 / 338	Olanzapine (n=159) and Clozapine (n=11). Antipsychotics divided into 2 groups according to their obesogenic and diabetogenic potential: highly anabolic (olanzapine and clozapine), and less anabolic drugs (the remaining antipsychotics).
Boden (Control unexposed, NOS), 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). Antipsychotics divided into 2 groups according to their obesogenic and diabetogenic potential: highly anabolic (olanzapine and clozapine), and less anabolic drugs (the remaining antipsychotics).
Bruno, 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 Olanzapine 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.	1400 / 197296	Denmark (1 January 2000–31 December 2018), Finland (1 January 2000–31 December 2016), Iceland (1 January 2004–31 December 2017), Norway (1 January 2005–1 December 2020), and Sweden (1 July 2006–31 December 2019).
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 onlanzapine only (without other 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).	110 / 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 onlanzapine only (without other 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.	110 / 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 filling at least one prescription of onlanzapine only (without other 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.	101 / 6476	Pregnancies with gestational age < 20 weeks, chromosomal abnormalities, fetal alcohol syndrome, abnormalities due to maternal infection, or exposure to known teratogens were excluded.
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 olanzapine during 1 month before pregnancy until the end of first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study).	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.	413 / 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 olanzapine during 1 month before pregnancy until the end of 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 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.	413 / 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.
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 Olanzapine during pregnancy; comedication with First Generation Antipsycotics (FGA) was allowed. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Women exposed to First Generation Antipsycotics (FGAs) excluding comedication with Second Generation Antipsycotics (SGA) (cohort I).	187 / 284	Primary analyse on all Atypical Antipsychotics but Raw data are provided for some substances. Cases with potentially embryo- or fetotoxic drugs were not excluded for both the study cohort and the comparison cohort I but were assessed afterward.
Habermann (Unexposed control), 2013	Germany 1997 - 2009	Subjects were enrolled through the consultation process at Teratology Information Service (TIS Berlin)	Women exposed to Olanzapine during pregnancy; comedication with First Generation Antipsycotics (FGA) was allowed. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Women exposed to teratogenic, fetotoxic, or insufficiently studied agents were excluded as described elsewhere (cohort II).	187 / 1122	Primary analyse on all Atypical Antipsychotics but Raw data are provided for some substances. Cases with potentially embryo- or fetotoxic drugs were not excluded for both the study cohort and the comparison cohort I but were assessed afterward.
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 Olanzapine 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.	3110 / 6455324	Overlapping: Data of Huybrechts 2016 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 Olanzapine 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.	2341 / 318731	Overlapping: Data of Huybrechts 2016 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 olanzapine. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Not specified	205 / -9	Partial overlapping between Kallen (1996 - 2011) et Huybrechts 2023 (Sweden: 2006-2016) for major malformations. Reis 2008 (1995-2005) almost totally included in Källen 2013 (1996-2011) => use of the largest one (Kallen).
McKenna, 2005	Canada, Israel and England Not specified	Women who contacted the line for information.	Women who has taken Olanzapine within 3 months of pregnancy or during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Subsequent woman who contacted the TIS regarding exposure to a non-teratogenic agent. Women who reported a psychiatric diagnosis or psychotropic medication use were excluded from the comparison group.	60 / 151	All of the women were exposed in the first trimester
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 Olanzapine for >5 elimination half-lives at delivery. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnant women receiving Haloperidol.	14 / 13	Each substance is a subanalyse. The meta-analysis authors considered Atypic antipsychotics as the exposed group and Haloperidol as the control group. In the original publication, the authors provided each outcome by Substance.
Ozturk, 2016	Turkey 2007 - 2012	Women referred to our prenatal consultation service for psychotropic drug exposure.	Pregnancies exposed to 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.	5 / 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.
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 Olanzapine (also received before pregnancy). Exclusion if more than 1 studied antipsychotic. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Pregnant women who had no prescriptions dispensed for an anti- psychotic medication during the first 140 days of pregnancy were classified as “discontinuers.”	375 / 978	Primary analyses performed individually for each substance (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone).
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 olanzapine throughout the pregnancy.	unexposed, disease free Women who not have any mental disorder and were not treated with any antipsychotics in the same department.	8 / 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.
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 Olanzapine 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).	770 / 1888130	The study not considered all major malformations but 26 malfo.
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 Olanzapine for a minimum of 4 weeks of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	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.	23 / 133
Sorensen, 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) Unexposed women were defined as pregnant women who did not redeem any prescription of antipsychotic medications during the exposure window.	223 / 841183	Primary analyses performed on antipsychotics versus unexposed. Authors also analysed each antipsychotic (typical and atypical) substance separately.
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 Olanzapine 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.	1495 / 3309095	Estimates from both cohorts were combined through meta-analysis by authors. Children with a known chromosomal or genetic abnormality were excluded.
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 Olanzapine filled between the conception date and the delivery date. At least one prescriptions filled prior to 27 GW. (This is a subgroup of exposure among the whole exposed group considered in the study).	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').	166 / 1021	Atypical antipsychotic drugs (and each substance) are a subgroup of the primary analysis on the antipsychotic drug. For those results, RRadj only provided on a graphic but raw data are provided by authors and used for this meta analysis.
Viguera, 2023	USA 2008 - 2022	Pregnant women with psychiatric diagnoses, aged 18 to 45 years, who are exposed and unexposed to Second-generation antipsychotics (SGAs) during pregnancy.	Pregnant women with first trimester use of Olanzapine.	unexposed, sick Pregnant women unexposed to Second-generation antipsychotics (SGAs) during the entire pregnancy.	47 / 1134	Clear chromosomal and single-gene abnormalities were excluded.
Wang - 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 Olanzapine before and during pregnancy (continuers).	unexposed, sick Pregnant women who did not receive any antipsychotic during pregnancy, but did before pregnancy (discontinuers).	-9 / 340	Number of Olanzapine continuers not provided by authors.
Wang - 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 Olanzapine before and during pregnancy (continuers).	unexposed, sick Pregnant women who did not receive any antipsychotic during pregnancy, but did before pregnancy (discontinuers).	-9 / 1577	Number of Olanzapine continuers not provided by authors.
Wurtz, 2017	Denmark 1997 - 2012	All singleton live-born children in Denmark from January 1, 1997 to December 31, 2012.	Any prescription of Olanzapine 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.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
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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