Aripiprazole - Medication and Pregnancy KB

Aripiprazole

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Bellet, 2015	France 2004 - 2011	Pregnant women who had contacted a TIS centre, directly or via their health care provider.	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) Patients included in the unexposed group were 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.
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 aripiprazole 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.	523 / 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).
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 aripiprazole 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.	220 / 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 aripiprazole 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.	220 / 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.
Freeman, 2021	USA 2008 - 2020	Pregnant women between the ages of 18 and 45 years with histories of psychiatric disorders.	Live birth of a women who had evaluable data and first trimester exposure to a aripiprazole.	unexposed, sick Live birth of a women unexposed to aripiprazole or other atypical antipsychotics during pregnancy.	163 / 704	Study of the NPRAA: Cohen 2016 (related to all atypical antipsychotics ; 2008 - 2014 ; n=214), Cohen 2018 (related to Quetiapine ; 2008 - 2017; n=155); Freeman 2021 (related to Aripiprazole; 2008 - 2020; n=163).
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 Aripiprazole 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).	60 / 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 (Control unexposed, disease free), 2013	Germany 1997 - 2009	Subjects were enrolled through the consultation process at Teratology Information Service (TIS Berlin)	Women exposed to Aripiprazole 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).	60 / 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 the Aripiprazole 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.	4523 / 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 the Aripiprazole 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.	3861 / 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).
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 Aripiprazole (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.”	419 / 1505	Primary analyses performed individually for each substance (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone).
Paulus, 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	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)
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 Aripiprazole 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).	790 / 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 Aripiprazole 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.	2 / 133
Sorensen, 2015	Denmark 1997 - 2008	Pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319)	Any prescription of Aripiprazole 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.	45 / 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 Aripiprazole 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.	1738 / 3309095	Estimates from both cohorts were combined through meta-analysis by authors. Children with a known chromosomal or genetic abnormality were excluded.
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 Aripiprazole 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 Aripiprazole continuers not provided by authors.

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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