Esomeprazole

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Broe (Controls unexposed, general pop), 2025	population based cohort retrospective	Exposure was determined using the Prescription register that contains individual-level prescription data from all Danish outpatient pharmacies.	Malformations were identified using infant records from three Danish health registries: The Birth register, the Patient register, and the Cause of Death Register during the first year of life.	Singleton only. Multivariable model including calendar year, maternal age at delivery, body mass index (BMI), smoking status, parity, and concurrent exposure to known teratogenic drugs during the first trimester.
Broe (Controls unexposed, sick), 2025	population based cohort retrospective	Exposure was determined using the Prescription register that contains individual-level prescription data from all Danish outpatient pharmacies.	Malformations were identified using infant records from three Danish health registries: The Birth register, the Patient register, and the Cause of Death Register during the first year of life.	Singleton only. Multivariable model including calendar year, maternal age at delivery, body mass index (BMI), smoking status, parity, and concurrent exposure to known teratogenic drugs during the first trimester.
Choi a, 2023	retrospective cohort (claims database)	Prescription database.	The presence of congenital malformations was identified via infants’ records and major malformations and their subtypes were defined based on the European Surveillance of Congenital Anomalies (EUROCAT) classification system (minor defects were excluded according to the EUROCAT exclusion list).	Propensity score: maternal age, income level, parity, multiple gestations, indications for PPIs (GERD, duodenitis...), maternal conditions (eg, anxiety, diabetes, and epilepsy), medication use (eg, opioid, NSAIDs), obstetric comorbidity index, and measures of health care use. Exclusion of exposures with known or potential teratogens. Sensitivity analyses: indications, singleton only, BMI, smoking.
Choi b, 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.
Pasternak, 2010	population based cohort retrospective	The Prescription Drug Register provided information on all esomeprazole prescriptions filled by women in the cohort between 4 weeks before conception and delivery.	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.

master protocol