Bupropion (All indications except smoking cessation)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Anderson, 2020	case control	Information on exposure to antidepressants and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants, conducted 6 weeks to 24 months after the EDD.	Case infants were ascertained through population-based birth-defects surveillance systems in 10 U.S. states. Controls were selected randomly from the same geographic areas. Clinical data were abstracted from medical records and classified by clinician geneticists and other clinicians.	Adjusted for maternal race/ ethnicity, prepregnancy body mass index, education, and early pregnancy smoking and alcohol use.
Chun-Fai-Chan (Controls exposed to other antidepressants), 2005	prospective cohort	The physicians or women are contacted and asked to prospectively complete exposure history, that included: medical indication, dose used, frequency of administration, gestational age at exposure.	Women or physicians were asked to complete a follow-up to ascertain pregnancy outcome. After the telephone administration of a follow- up questionnaire, the researcher sent a letter to the patient’s physician asking for verification of the information obtained from the questionnaire.	Control group matched on the age of the participant, alcohol consumption, smoking and gestational age at the time of call.
Chun-Fai-Chan (Controls unexposed, NOS), 2005	prospective cohort	The physicians or women are contacted and asked to prospectively complete exposure history, that included: medical indication, dose used, frequency of administration, gestational age at exposure.	Women or physicians were asked to complete a follow-up to ascertain pregnancy outcome. After the telephone administration of a follow- up questionnaire, the researcher sent a letter to the patient’s physician asking for verification of the information obtained from the questionnaire.	Control group matched on the age of the participant, alcohol consumption, smoking and gestational age at the time of call.
Cole, 2007	retrospective cohort (claims database)	Use of the claims for prescription dispensings along with membership data.	Searches of the medical claims data for the corresponding ICD-9 diagnosis codes. All malformations confirmed through medical record abstraction. Trained nurses, blinded to the study hypothesis and maternal exposure status, conducted the medical record abstractions.	For major malfo and cardiac malfo: adjusted for maternal age category, geographic region of the health plan, infant sex, diagnoses eclampsia within 1 year before delivery, dispensings of lithium, phenytoin, fluconazole within 1 year before delivery through the end of the first trimester, and number of physician visits within 10–12 months before delivery.
Einarson, 2009	prospective cohort	During the initial telephone contact, details of exposure and concurrent exposures are recorded on a standardized questionnaire.	At the follow-up interview, gestational findings, fetal outcomes, and neonatal health are documented on a structured form by telephone interview with each mother. The details are then corroborated with the report of the physician caring for the baby.	No adjustment/no matching for this group of exposure (the 2 whole groups were matched for maternal age, smoking, and alcohol use).
Figueroa, 2010	retrospective cohort (claims database)	The MarketScan data contain information including prescription claims and the date of the service.	Outpatient and inpatient claims with a primary or secondary diagnosis of ADHD and prescription claims for stimulants, determined by national drug coding, were identified.	Controlled for demographic and perinatal factors (including maternal age group, gender of the child, urban or rural metropolitan statistical area, year of birth, and age at last claim and at end of eligibility), parental mental health diagnoses, the use of other psychotropics during pregnancy, and maternal mental health visits by year of the child’s life.
Huybrechts (Controls unexposed, NOS), 2014	retrospective cohort (claims database)	The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions.	The Medicaid Analytic eXtract data set that contains data on all physician services and hospitalizations and the accompanying diagnoses and procedures. Congenital cardiac malformations were identified on the basis of International Classification of Diseases (ICD-9) codes.	None.
Huybrechts (Controls unexposed, sick), 2014	cohort	The Medicaid Analytic eXtract data set that contains data on all filled outpatient medication prescriptions.	The Medicaid Analytic eXtract data set that contains data on all physician services and hospitalizations and the accompanying diagnoses and procedures. Congenital cardiac malformations were identified on the basis of International Classification of Diseases (ICD-9) codes.	Adjusted for the high-dimensional propensity score: including year of delivery, age, race, multiple gestation, antidepressant indications, proxies for depression severity, other chronic maternal illness, other psychotropic medication use, antidiabetic, antihypertensive and residual confounding for proxies of unmeasured confounders.
Jackson, 2024	retrospective cohort (claims database)	Medication exposure was determined by its presence or absence in the medication reconciliation document completed during hospital admission.	Clinical data were obtained from the inpatient electronic medical record system. Outcome was determined by the presence of an ICD-10 diagnosis code for postpartum hemorrhage (PPH) and a procedure code for blood transfusion.	Adjustment on induction of labor, multiple gestation, >4 previous vaginal births, prior cesarean or uterine incision, large uterine fibroids, fetal demise, polyhydramnios, placental abruption, placenta accreta, placenta previa, known coagulopathy, anemia (hematocrit <30%), and thrombocytopenia, advanced maternal age, obesity, public health insurance, and race and ethnicity group.
Kjaersgaard, 2013	population based cohort retrospective	Information on all redeemed prescriptions was obtained from the Denmark Registry of Medicinal Product Statistics.	Clinically recognized abortions were identified in the Danish National Hospital Registry, that contains data on in- and outpatient contacts in Denmark coded according to a Danish version of the 10th revision of the International Classification of Diseases (ICD-10).	No adjustment for this group of exposure.
Laspro, 2024	nested case control	Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy.	Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records.	None.
Louik, 2014	case control	Mothers are invited to participate in a telephone interview after delivery, conducted by trained nurses who are unaware of the study hypotheses. It collects detailed data on all medications (prescription, over-the-counter, ...) used anytime from 2 months prior to conception through the pregnancy.	Research staff identify malformed subjects by reviewing hospital admission and discharge lists or from statewide birth-defect registries and mothers of non-malformed infants were identified at study hospitals and from a population-based random sample of newborns in Massachusetts.	Controls matched to cases on age within 2 months. Adjusted for study center, family history of birth defect and/or last menstrual period (LMP).
Marks (Controls exposed to Sertraline), 2021	retrospective cohort	Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis.	Diagnoses were extracted from the electronic database discharge summaries, delivery records, and/or International Classification of Diseases (ICD) codes. Clinical diagnosis were extracted from the delivery discharge summary written by the clinician caring for the infant.	All results reported as aOR (95% CI) controlling for maternal race, age, insurance, and gestational age at delivery.
Marks (Controls unexposed, sick), 2021	retrospective cohort	Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis.	Diagnoses were extracted from the electronic database discharge summaries, delivery records, and/or International Classification of Diseases (ICD) codes. Clinical diagnosis were extracted from the delivery discharge summary written by the clinician caring for the infant.	All results reported as aOR (95% CI) controlling for maternal race, age, insurance, and gestational age at delivery.
Newport, 2016	nested case control	Prospective documentation of medication exposure recording the daily dose of all agents on a week-by-week basis across gestation.	Outcome ascertainment was determined via structured abstraction of the obstetrical record by an experienced obstetrical nurse.	No adjustment for this exposure.
Ozturk, 2016	prospective cohort	At the first contact, initiated via gynecologists, a detailed patient history form was used to notably record all drug exposures (dose, duration and timing in pregnancy).	Each newborn baby was checked at birth for signs of problems or complications.	None
Palmsten (control exposed to SSRIs), 2013	retrospective cohort (claims database)	Outpatient pharmacy-dispensing data.	Medicaid enrollment information was linked to inpatient and outpatient procedures and diagnoses. Outcome validity was assessed by reviewing delivery hospital medical records for a sample of 183 women. Preeclampsia defined with ICD-9 code for preeclampsia or eclampsia (642.4x–642.7x).	No adjustment for this group of comparison.
Palmsten (Controls unexposed, sick), 2013	retrospective cohort (claims database)	Outpatient pharmacy-dispensing data.	Medicaid enrollment information was linked to inpatient and outpatient procedures and diagnoses. Outcome validity was assessed by reviewing delivery hospital medical records for a sample of 183 women. Preeclampsia defined with ICD-9 code for preeclampsia or eclampsia (642.4x–642.7x).	Adjusted for delivery year, preeclampsia risk factors (age, race/ethnicity, primiparity, diabetes, multifetal gestation, pain-related diagnosis...), depression severity proxies, other antidepressant indications, other medications, and healthcare utilization.
Palmsten b, 2013	retrospective cohort (claims database)	Data of prescription.	Women with an ICD-9 code for 666.x during the admission to hospital for delivery, or within three days after the delivery date, were classified as having postpartum hemorrhage. Atonic postpartum hemorrhage only (666.1x) and inpatient postpartum hemorrhage only, also considered.	Adjusted for delivery year, age, race, multiple pregnancy, diabetes, coagulopathy, number of outpatient and inpatient mood/anxiety disorder diagnoses, other mental health disorder, pain indication, sleep disorder, anticonvulsant, benzodiazepine, aspirin, heparin, low molecular weight heparin and warfarin dispensing, and number of outpatient visits and days in hospital during baseline.
Suarez (Controls unexposed, discontinuers), 2022	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications.	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on diagnoses, and procedures received dur- ing all health care encounters, including all inpatient, out- patient, or emergency department visits.	Illness. Adjusted for age, race/ethnicity (MAX only), delivery year, antidepressant indications, proxies for severity of mental conditions, smoking, alcohol/substance abuse, other medications, overweight/obesity, pregestational diabetes, pregestational hypertension, county-level socioeconomic indicators (MAX only), prenatal vitamin use, multiple gestation pregnancy, parity (MAX only), ...
Suarez (Controls unexposed, general pop), 2022	retrospective cohort (claims database)	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on dispensed outpatient prescription medications.	The Medicaid Analytic eXtract (MAX) and the MarketScan Commercial Claims Database (MarketScan), that include information on diagnoses, and procedures received dur- ing all health care encounters, including all inpatient, out- patient, or emergency department visits.	Adjusted for age, race/ethnicity (MAX only), delivery year, antidepressant indications, proxies for severity of mental conditions, smoking, alcohol/substance abuse, other medications, overweight/obesity, pregestational diabetes, pregestational hypertension, county-level socioeconomic indicators (MAX only), prenatal vitamin use, multiple gestation pregnancy, parity (MAX only), ...
Thyagarajan, 2012	retrospective cohort (claims database)	Use of the claims for prescription dispensings along with membership data.	Searches of the medical claims data for the corresponding ICD-9 diagnosis codes. All malformations confirmed through medical record abstraction. Trained nurses, blinded to the study hypothesis and maternal exposure status, conducted the medical record abstractions.	No adjustment for this outcome.
Yaris, 2005	prospective cohort	Data surveyed by the interviews.	Examinations were made by obstetric ultrasound for the mothers and birth weight and height, gestational age, APGAR scores, congenital malformation and developmental problems for the babies. Periodic checks of all the babies in the neonatal period, were made the first year, and following years.	None for this group of exposure.
Yeh, 2021	retrospective cohort (claims database)	The Taiwan National Health Insurance Research Database (THIRD) provides prescriptions information about insured individuals.	The THIRD provides diagnosis information about insured individuals. Psychiatric disorders were diagnosed based on clinical judgement and interviews by psychiatrists. In this study, the diagnosis of ADHD and ASD required at least twice outpatient visits within each year for these ICD-9 codes.	Adjusted for demographic characteristics (the level of urbanization, monthly income, and other demographics).

master protocol