Tramadol (versus unexposed)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bowie, 2022	population based cohort retrospective	Records of prescribed prenatal opioid analgesics in the Narcotic Monitoring System (NMS) database. Records information on controlled drug prescriptions issued to Ontario residents.	Diagnosis codes from the Canadian version of the International Classification of Diseases, 10th Revision in the Hospital Discharge Abstract Database, the Same Day Surgery Database and the National Ambulatory Care Reporting System Database.	High-dimensional propensity scores (HDPS): gestational parent age, parity, socioeconomic status quintile, Elixhauser comorbidity score, diabetes, obesity, hypertension, pain, other prescribed psychotropic medications (only data on benzodiazepines or barbiturates were available), and year of delivery. And diagnostic codes in the year prior to pregnancy (OHIP database).
Ferrer, 2025	retrospective cohort (claims database)	Data on reimbursed medications prescribed and dispensed to patients, as well as the dates of conception and pregnancy outcome, were obtained from the French health insurance system.	Data on the children were obtained from the children's medical certificates completed recorded by the Mother and Child Protection Centre. Data on hospital admissions and pregnancy terminations were obtained from the Toulouse University Hospital Centre and the French health insurance system.	No adjustment, except for Major congenital anomalies and Spontaneous pregnancy termination: adjusted for maternal age, dispensation of folic acid, teratogenic drugs, NSAIDs (nonsteroidal anti-inflammatory drugs), presence of hypertension, diabetes, and long-term adverse health condition.
Gouraud, 2010	prospective cohort	The first contact to the pharmacovigilance center took place before week 22 after the last menstrual period then contacted by mail or phone after the expected date of delivery.	Contacted by mail or phone after the expected date of delivery regarding any event occurring during pregnancy, the pregnancy outcome and full data on the neonate including birth defects and neonatal pathologic conditions. Hospital discharge summaries were requested for detailed information.	Adjustment none because to much confounding factors with missing data. Matched for age and gestational age at time of first request only for spontaneous abortion.
Källén, 2015	population based cohort retrospective	Interviews made by midwives at the first antenatal care visit of the pregnant woman, in most cases during weeks 10–12.	The Medical Birth Register contained neonatal diagnoses given by the pediatrician which examined the newborn baby. Major malformations were reported to the Birth Defect Register and could also be identified from discharge diagnoses after hospitalizations in the Patient Register.	Adjustment for year of delivery, maternal age and parity, maternal smoking in early pregnancy, and Body mass index before pregnancy.
Sørensen, 2022	population based cohort retrospective	Gathered from the Danish National Prescription Register.	Informations extracted from The Danish National Patient Register. Major congenital malformations were classified according to the European Surveillance of Congenital Anomalies guide 1.4.	Propensity scored matching in a ratio of up to 1:4 including age, socioeconomic status, previous pregnancy history (parity and previous event of interest), smoking, prescription drug use as a proxy for morbidity (eg, antidiabetic drugs, antihypertensives, thyroid drugs, Non-steroidal anti-inflammatory drugs (NSAIDs), opioid etc.) and health care use in the year before the date of conception.

master protocol