Clozapine

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Huybrechts (Controls unexposed, NOS), 2023	population based cohort retrospective	Exposure to atypical and typical antipsychotics was defined based on filling 1 or more prescriptions of the respective drug class during the first trimester, the period for organogenesis. => Prescription databases.	Nordic Countries: outcomes are defined based on data from the Medical Birth, Malformation and/or Patient Registers from the date of birth to one year after birth. USA: claims in infant record between birth and birth more 90 days and/or in the maternal record, using both in- and out-patient data.	Propensity score approach to control for potential confounders: demographic factors (maternal age..), treatment indications/mental disorders, maternal/obstetrical conditions (hypertension, diabetes, ...), lifestyle behaviors (tobacco, alcohol, ...), other medications, and health care utilization metrics. Exclusion of pregnancies exposed to a known teratogenic medication. Singleton births only.
Huybrechts (Controls unexposed, sick), 2023	population based cohort retrospective	Exposure to atypical and typical antipsychotics was defined based on filling 1 or more prescriptions of the respective drug class during the first trimester, the period for organogenesis. => Prescription databases.	Nordic Countries: outcomes are defined based on data from the Medical Birth, Malformation and/or Patient Registers from the date of birth to one year after birth. USA: claims in infant record between birth and birth more 90 days and/or in the maternal record, using both in- and out-patient data.	Propensity score approach to control for potential confounders: demographic factors (maternal age..), treatment indications/mental disorders, maternal/obstetrical conditions (hypertension, diabetes, ...), lifestyle behaviors (tobacco, alcohol, ...), other medications, and health care utilization metrics. Exclusion of pregnancies exposed to a known teratogenic medication. Singleton births only.
Kulkarni, 2024	prospective cohort	Pregnant women were interviewed and monitored by the research team. With consent, information was also sought from treating clinicians and medical records.	Pregnant women were interviewed and monitored by the research team. With consent, information was also sought from treating clinicians and medical records.	No adjustment. The confounding variables were analyzed using univariate models with just 1 explanatory variable at a time.
McKenna, 2005	prospective cohort	Exposure declared by women during exposure and data were achieved by sending each general practitioner a detailed questionnaire with questions regarding drug history.	This was achieved by sending each general practitioner a detailed questionnaire with questions regarding pregnancy outcome. Once the questionnaire was completed, permission was requested to receive a report from the physician primarily caring for the infant.	No adjustment/match for this exposed group.
Peng, 2013	prospective cohort	A detailed questionnaire completed by all enrolled pregnant women prior to delivery. Once the questionnaire was completed, permission was requested to receive a report from the physician and obstetrician.	The Bayley-III was administered by a psychologist who specialized in this scale and assessed neurodevelopment of children for the hospital. The psychologist was not a part of research team and was blinded during all neurobehavioral development assessments	No adjustment/match for this exposed group.
Reis (Control exposed to FGA), 2008	population based cohort retrospective	Maternal drug use in early pregnancy is recorded from interviews performed by the midwife at the first antenatal care visit, usually before the end of the first trimester.	3 national health registers: the Medical Birth Register, the Swedish Register of Congenital Malformations, and the Hospital Discharge Register	No adjustment for this exposed group.
Reis (Unexposed control, NOS), 2008	population based cohort retrospective	Maternal drug use in early pregnancy is recorded from interviews performed by the midwife at the first antenatal care visit, usually before the end of the first trimester	3 national health registers: the Medical Birth Register, the Swedish Register of Congenital Malformations, and the Hospital Discharge Register	No adjustment for this exposed group.

master protocol