Risperidone Paliperidone

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
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 risperidone 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.	294 / 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 risperidone 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).	69 / 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 risperidone 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.	69 / 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 risperidone 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.	49 / 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 risperidone 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.	242 / 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 risperidone 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.	242 / 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.
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 Risperidone 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.	2798 / 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 Risperidone 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.	2270 / 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).
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 Risperidone 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.	6 / 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 Risperidone. (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.	2 / 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 Risperidone (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.”	343 / 1449	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 risperidone throughout the pregnancy.	unexposed, disease free Women who not have any mental disorder and were not treated with any antipsychotics in the same department.	16 / 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 Risperidone 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).	507 / 1888130	The study not considered all major malformations but 26 malfo.
Reis (Control exposed to FGA), 2008	Sweded 1995 - 2005	Whole country (1.4% of all deliveries in Sweden are missing in the register).	Women who had reported the use of Risperidone 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).	51 / 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 (Unexposed control, 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 Risperidone 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.	51 / 958729	Atypical antipsychotics are a subgroup of the entire study. OR and adjustement 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 Risperidone or Paliperidone 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.	15 / 133	Women who were exposed to teratogenic medications unrelated to their psychiatric disorder treatment, such as acutane, or who abused substances (eg, alcohol, marijuana, cocaine, heroin, etc) were excluded from the study cohort.
Shechtman (Control exposed to Haloperidol), 2009	Israel 1999 - 2007	Callers who were counseled by these TISes between 1999 and 2007.	Pregnant women who call who the TISes in regard to risperidone exposure during pregnancy.	exposed to other treatment, sick Pregnant women, disease-matched control (DMC) who were counseled in the same time frame about exposure to another antipsychotic drug, haloperidol, with more data on its safe use in pregnancy.	106 / 86
Shechtman (Unexposed control), 2009	Israel 1999 - 2007	Callers who were counseled by these Teratology Information Services between 1999 and 2007.	Pregnant women who call who the Teratology Information Services in regard to risperidone exposure during pregnancy.	unexposed (general population or NOS) Pregnant women who were randomly selected among women counseled in the same time frame for non-teratogenic (NTC) exposures.	106 / 448
Sorensen, 2015	Denmark 1997 - 2008	Pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319).	Any prescription of Risperidone 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.	116 / 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 Risperidone 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.	1404 / 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 Risperidone 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').	112 / 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.
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 Risperidone 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 Risperidone continuers not provided by authors.
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 Risperidone 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.	2 / 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
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 individu- ally matched to the cases (3:1).	44118 / 132317

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