Omeprazole

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bànhidy, 2011	case control	Mothers were mailed a questionnaire (after the selection of cases and controls) requested information on medicinal products taken during pregnancy and to send their prenatal maternity logbook which related drug prescriptions. Regional nurses were asked to visit and question the non-respondent.	Mothers were asked to send their prenatal maternity logbook and other medical records concerning their diseases during the pregnancy and their child’s CA. A questionnaire was also mailed requesting the same informations. Regional nurses were asked to question the non-respondent.	In general, two controls were matched to every case according to sex, birth week, and district of parents’ residence. Potential confounders were maternal age (<25 years, 25–29 years, and 30 years or more), birth order (ﬁrst delivery or one or more previous deliveries), employment status, PUD-related drugs (yes/no), and use of folic acid supplement (yes/no).
Choi, 2023	retrospective cohort (claims database)	Prescription database.	The National Health Insurance Service (NHIS) database.	Propensity score: maternal age, medical aid, income level, parity, multiple gestations, indications for PPIs (GERD, duodenitis...), maternal conditions (eg, anxiety, diabetes, and epilepsy), other medication prescription, obstetric comorbidity index, and measures of health care use. Sensitivity analyses: indications, singleton only, body mass index, smoking, sibling design, first-time pregnancy.
Diav-Citrin, 2005	prospective cohort	Details of exposure were collected during pregnancy before pregnancy outcome was known, using a structured questionnaire.	After the expected date of delivery, follow-up was conducted with the woman, her physician or midwife by a telephone interview and/or mailed questionnaire to obtain details on the pregnancy outcome.	None.
Källén, 2001	population based cohort retrospective	The pregnant women are interviewed by a midwife during the first visit to the antenatal clinic. During the continued antenatal care, further drug use is recorded at the attendance of the woman to the antenatal care centers.	Outcome of the deliveries were studied in the Medical Birth Registry and compared with data from all births in the register.	Year of birth, maternal age, parity, and maternal smoking habits.
Källén, 2003	population based cohort retrospective	At the ﬁrst antenatal visit (usually week 10–12), a midwife interviewed the woman on the use of drugs during the pregnancy before the antenatal care visit. Throughout the subsequent antenatal care, additional prescriptions for drugs are recorded and also computerized.	Infants with cardiovascular defects were identiﬁed from three sources: The Swedish Medical Birth Registry, the Swedish Registry of Congenital Malformations and the Swedish Child Cardiology Registry. Pregnancy outcome information was obtained from the delivery and pediatric records.	Stratiﬁcation for year of birth and possible confounders: maternal age, parity, smoking habits in early pregnancy, and years of involuntary childlessness.
Källèn (Controls exposed to other treatment, sick), 1998	population based cohort retrospective	At the first visit to the antenatal clinic (usually during weeks 10-12), the pregnant woman is interviewed by a midwife on drugs taken after the time the woman became pregnant and before the antenatal visit.	Malformations which has been reported to the Medical Birth Registry completed by the data of the Registry of Congenital Malformation and the Child Cardiology Register.	Stratification was made for year of birth (1997 births were compared with 1996 population as no final population data for 1997 were available), maternal age, parity and smoking habits in early pregnancy.
Kerr, 2018	case control	Within 6 months of delivery, nurse interviewers contacted mothers to complete a computer-assisted telephone interview to collect a detailed history of the pregnancy including illnesses and medications.	Cases and controls were ascertained at participating hospitals or birth defect registries in the same areas.	Study center, time period, maternal race/ethnicity, age and education (aORs were calculated when there were five or more exposed cases).
Lalkin (Controls exposed to other treatment, sick), 1998	prospective cohort	Standardized data collection forms were used to obtain information by telephone or clinic interview. The controls were selected from the Motherisk database.	Each woman was recontacted regarding pregnancy outcome.	Each woman exposed was subsequently matched to 2 controls. All cases were match for maternal age, smoking pattern and alcohol consumption.
Lalkin (Controls unexposed NOS), 1998	prospective cohort	Standardized data collection forms were used to obtain information by telephone or clinic interview. Controls were selected from the Motherisk database.	Each woman was recontacted regarding pregnancy outcome.	Each woman exposed was subsequently matched. All cases were match for maternal age, smoking pattern and alcohol consumption.
Lind, 2013	case control	The National Birth Defects Prevention Study uses computer-assisted telephone interviews to collect information from women 6 weeks to 24 months after their estimated date of delivery.	Cases are identified through population-based birth defects surveillance from each states. A clinical geneticist classifies eligible cases of hypospadias as isolated.	Adjusted for maternal age, race/ethnicity, education, pre-pregnancy BMI, previous live births, sub-fertility, study site, and year of due date.
Matok, 2012	retrospective cohort (claims database)	Electronic database of medications dispensed by ‘‘Clalit’’ pharmacies.	Two electronic databases of SMC (Soroka Medical Center) comprising one with clinical information from the Department of Obstetrics and Gynecology, and one with demographic and hospitalization data, and an SMC registry of medical pregnancy terminations with information collected manually.	Maternal age, parity, self-reported smoking status during pregnancy, maternal diabetes mellitus, year of birth, and population group (i.e., Jewish or Bedouin Muslim). Peripartum fever (deﬁned as a temperature of 38°C or higher) and pregnancy duration in days were added to the covariates for pregnancy outcomes other than congenital malformations.
Moretti, 2001	prospective cohort	Not specified.	Ascertaining pregnancy outcome with direct interview with the mother.	Not specified.
Pasternak, 2010	population based cohort retrospective	The Prescription Drug Register provided information on all omeprazole prescriptions filled by women in the cohort between 4 weeks before conception and delivery. (Omeprazole and Lansoprazole became OTC in 2006 and 2007 respectively).	Cases of birth defects were identified with the use of the National Patient Register and a random sample had a medical records review. Major birth defects were defined according to the EUROCAT classification.	No potential confounder stood out as an important one, therefore, as an alternative all potential confounders and their effect were sum up into one variable: the propensity score.
Ruigomez (Controls exposed to other treatment, sick), 1999	retrospective cohort	Italy: Computer files registered in the output registration database. UK: Prescriptions issued by the general practitioner are directly generated by the computer system.	UK and Italy: medical records (and hospital discharge letters in UK and birth certificate in Italy).	Adjustment was made for the mothers's age and prematurity.
Ruigomez (Controls unexposed NOS), 1999	retrospective cohort	Italy: Computer files registered in the output registration database. UK: Prescriptions issued by the general practitioner are directly generated by the computer system.	UK and Italy: medical records (and hospital discharge letters in UK and birth certificate in Italy).	Adjustment was made for the mothers's age and prematurity.
Van Gelder, 2022	prospective cohort	Data on medication exposures were obtained from the three prenatal Web-based questionnaires (at baseline and in gestational weeks 17 and 34) and the first postpartum questionnaire. Proton Pump Inhibitor exposure was defined as report of medication belonging to ATC group A02BC.	Participating women were asked to complete Web-based questionnaires at multiple time points postpartum, notably to gather data on pregnancy complications and infant health. Participants were asked consent for obtaining records from prenatal care providers.	Adjustment for a minimally sufficient set of confounders identified using directed acyclic graphs: maternal age, parity, pre-pregnancy Body Mass Index (BMI), maternal asthma, maternal depression, and smoking, alcohol consumption, and any use of calcium-containing supplements during pregnancy. In a sensitivity analysis, women with chronic hypertension (N=85) were excluded from the analyses.

master protocol