- Medication and Pregnancy KB

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bateman - Calcium blockers, 2015	retrospective cohort (claims database)	Exposure was defined based on filled prescriptions.	The study outcome was defined by the presence of one or more diagnostic codes indicating neonatal seizure (code 779.0x in ICD-9) in the infants record from date of birth to day of life 90.	Propensity score in a fixed 1 to 3 ratio using a nearest neighbor algorithm, on maternal age, race/ethnicity; pre-existing hypertension, gestational hypertension, preeclampsia, pre-existing diabetes, gestational diabetes, chronic renal disease, threatened premature labor, illicit drug, alcohol abuse, tobacco, multiple gestation; maternal medications, maternal comorbidity... Term infants only.
Bayliss - Calcium blockers, 2002	retrospective cohort	Clinical data are collected on drug treatment used before and during pregnancy. Data is collected prospectively from the clinics (patient’s hospital records) onto a proforma and entered into a computer database by a research associate (MB).	Clinical data are collected on the pregnancy outcome, including parameters of fetal growth and wellbeing. Data is collected prospectively from the clinics (patient’s hospital records) onto a proforma and entered into a computer database by a research associate (MB).	No adjustment for this group of exposure.
Bortolus - Nifedipine, 2000	randomized controlled trial	Eligible women were randomly assigned treatment group. Group allocation was done by telephone to the Istituto Mario Negri in Bergamo. The randomisation list was generated by computer. Separate randomisation lists were used for each centre and type of hypertension.	A postal questionnaire was sent to the parents which asked about the child‘s general health, height, weight, malformations, respiratory, hearing, and vision problems, and other major disorders. Other questions concerned the child’s gross and fine motor and language development.	No adjustment. Randomisation. Exclusion of women history of chronic diseases such as diabetes or renal disease, documented fetal malformations, antihypertensive treatment if not interrupted before the eighth week of gestation.
Caton - Calcium blockers, 2009	case control	Data were collected via a computer-assisted telephone interview of infant's mothers within 24 months of the expected delivery date. Interviewers asked detailed questions about the diagnosis, timing, and treatment of high blood pressure.	Case infants were identified from the population-based birth defects surveillance systems of the participating centers. Control infants were randomly selected from birth certificates or hospital discharge listings in the same geographic areas as the cases.	ORs were adjusted for study center, maternal age at delivery, prepregnancy body mass index, and gestational diabetes.
Darcie - Isradipine, 2004	prospective cohort	This was a randomized, longitudinal, prospective study comparing 3 groups of patients according to the type of maternal treatment. => Not otherwise specified => Considered as a prospective cohort because no precision indicating that a randomization was carried out.	All newborn were specifically evaluated at birth and then successively in the first 24 hours of birth.	No adjustment. Singleton pregnancy. Exclusion of mothers who had another pathology (such as cardiopathy, hepatopathy, hemopathy, diabetes, or pneumopathy) or had been taking other medications that could interfere with the metabolism of carbohydrates in the newborn.
Fisher - Calcium blockers (Controls unexposed, disease free), 2017	case control	Trained interviewers collected data via telephone interviews between 6 weeks and 24 months after the estimated delivery date. The interview included notably questions on medication use during the three months before pregnancy until delivery.	Case infants were identified from the population-based birth defects surveillance systems of the participating centers. Control infants were randomly selected from birth certificates or hospital discharge listings in the same geographic areas as the cases. (According to Caton 2009)	For 5 and more exposed cases: adjusted for maternal race/ethnicity, body mass index, age, early pregnancy smoking, and study site. Otherwise, not adjusted. Exclusion of mothers who reported preexisting type 1 or type 2 diabetes mellitus, and mothers with a multiple birth. Cases with a known pathogenesis (eg, recognized single gene disorder or chromosomal abnormality) were excluded.
Fisher - Calcium blockers (Controls unexposed, sick), 2017	case control	Trained interviewers collected data via telephone interviews between 6 weeks and 24 months after the estimated delivery date. The interview included notably questions on medication use during the three months before pregnancy until delivery.	Case infants were identified from the population-based birth defects surveillance systems of the participating centers. Control infants were randomly selected from birth certificates or hospital discharge listings in the same geographic areas as the cases. (According to Caton 2009)	For 5 and more exposed cases: adjusted for maternal race/ethnicity, body mass index, age, early pregnancy smoking, and study site. Otherwise, not adjusted. Exclusion of mothers who reported preexisting type 1 or type 2 diabetes mellitus, and mothers with a multiple birth. Cases with a known pathogenesis (eg, recognized single gene disorder or chromosomal abnormality) were excluded.
Fisher a - Calcium blockers, 2018	case control	Exposure information was collected via maternal self-report during a computer-assisted telephone interview administered between 6 weeks and 24 months after her estimated delivery date. Trained interviewers asked about medication use during the 3 months before pregnancy until delivery.	Data were abstracted from medical record, birth certificates or hospital discharge records.	For case groups with at least 5 exposed cases, estimates are adjusted for maternal age, race/ethnicity, body mass index, parity, pregestational type 1 or type 2 diabetes, and study site.
Fisher b - Calcium inhibitors (Controls unexposed, disease free), 2018	retrospective cohort	Trained interviewers collected data via telephone interview within 24 months of the infant’s birth. The interview included questions on medication use during the 3 months before pregnancy until delivery.	Infant sex and gestational age were obtained from the infant’s birth record.	No adjustment for this group of exposure. Singletons only. Exclusion of mothers who reported preexisting diabetes.
Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018	retrospective cohort	Trained interviewers collected data via telephone interview within 24 months of the infant’s birth. The interview included questions on medication use during the 3 months before pregnancy until delivery.	Infant sex and gestational age were obtained from the infant’s birth record.	No adjustment for this group of comparison. Exclusion of mothers who reported preexisting diabetes.
Fitton - Calcium Blockers, 2021	retrospective cohort (claims database)	The Prescribing Information System which collects information on encashed prescriptions issued by primary care and dispensed from community pharmacies for all Scottish residents.	The Scottish Morbidity Record databases: data on maternal, obstetric, child outcomes and all admissions to acute hospitals; and the Child Health Systems Programme Pre-School, which includes data on special needs and developmental outcomes, routinely collected at 10 days, 6–8 weeks and 27–30 months.	Regressions were adjusted for relevant confounders as identified by directed acyclic graphs (DAG) process. All models were adjusted for: maternal BMI, Scottish Index of Multiple Deprivation (SIMD), smoking, diabetes, previous stillbirths, parity, illicit drug use, recorded diagnosis of preeclampsia during the current pregnancy and maternal age. Only singleton live birth.
Fitton - Calcium blockers (Controls unexposed, disease free), 2020	retrospective cohort (claims database)	The Prescribing Information System which collects information on encashed prescriptions issued by primary care and dispensed from community pharmacies for all Scottish residents.	The Scottish Morbidity Record 02 database, which collects data on maternal, obstetric, and child outcomes.	Adjusted for: Maternal body mass index, maternal diabetes, parity, smoking status, maternal age, preeclampsia, Scottish Index of Multiple Deprivation (SIMD) quintile, drug misuse, alcohol intake, previous stillbirths and interactions. Only singleton live birth.
Fitton - Calcium blockers (Controls unexposed, sick), 2020	retrospective cohort (claims database)	The Prescribing Information System which collects information on encashed prescriptions issued by primary care and dispensed from community pharmacies for all Scottish residents.	The Scottish Morbidity Record 02 database, which collects data on maternal, obstetric, and child outcomes.	No adjustment for this group of comparison. Only singleton live birth.
Ishikawa - Amlodipine (Controls unexposed, disease free), 2023	retrospective cohort (claims database)	A large administrative claims database from JMDC Inc. (Tokyo, Japan), which contained all the inpatient, outpatient, and pharmacy claims received from insurers. These claims include prescribed medications.	A large administrative claims database which contained all the inpatient and outpatient received from insurers (including diagnoses, surgical and medical procedures). The major malformations in claims were validated against patient medical records: the overall predictive positive value was 91.5%	No adjustment for this group of comparison. Exclusion of multiple deliveries and infants who had chromosomal abnormalities.
Ishikawa - Amlodipine (Controls unexposed, sick), 2023	retrospective cohort (claims database)	A large administrative claims database from JMDC Inc. (Tokyo, Japan), which contained all the inpatient, outpatient, and pharmacy claims received from insurers. These claims include prescribed medications.	A large administrative claims database which contained all the inpatient and outpatient received from insurers (including diagnoses, surgical and medical procedures). The major malformations in claims were validated against patient medical records: the overall predictive positive value was 91.5%	No adjustment for this group of comparison. Exclusion of multiple deliveries and infants who had chromosomal abnormalities.
Lennestal - Calcium inhibitors, 2009	population based cohort retrospective	Maternal use of drugs during pregnancy based on the midwife interview at the first antenatal visit (90% of women attend before week 12) and therefore mainly refers to first trimester exposure.	The Swedish Medical Birth Register, the Congenital Malformation Register, and the Hospital Discharge Register.	Adjusted for year of birth, maternal age, parity, smoking, and body mass index (BMI). Women with a diagnosis of diabetes were removed from the analysis. For neonatal outcomes: analysis also performed for 'Only term infants'.
Magee - Calcium blockers, 1996	prospective cohort	Standardized data collection forms were used to collect information by telephone or clinic interview, including drug exposure of interest (i.e., caIcium channel blocker dose, timing, toxicity, and indication for therapy) and concurrent drug or physical exposures.	After the expected date of delivery, follow-up was conducted by either telephone interview or mailed questionnaire to the patient (depending on the center) to obtain details of labor and delivery, neonatal complications, and posnatal growth and development.	Controls were matched to cases according to maternal age (2 years period) and smoking. No significant differences were found between the 2 groups for maternal age, ethnicity, marital status, obstetric history, or smoking.
Mito - Amlodipine, 2019	retrospective cohort	Data extracted from mothers’ electronic health records.	Clinical information, such as birth date, underlying disease, past medical history, previous pregnancy complications, family history, as well as information on the course of the index pregnancy and the newborn, were obtained from electronic medical records.	No adjustment. Singleton only. A subgroup analysis after excluding women with diabetes mellitus remained similar. No statistical difference for Body mass index, Diabetes mellitus, smoking and alcohol consumption during pregnancy.
Nakhai-Pour - Calcium blockers, 2010	nested case control	The Régie de l’Assurance Maladie du Québec (RAMQ) provides prospectively collected data on filled prescriptions.	The three administrative databases provided data on physician-based diagnosis (according to ICD-9), physician and emergency department visits and admissions, procedures and hospitalizations, health care providers, birth weight and gestational age for live births and stillbirths.	No adjustment for this group of exposure. Singleton only. Exclusion of pregnant women who were exposed to known teratogens.
Parazzini - Nifedipine, 1998	randomized controlled trial	Eligible women were randomly assigned treatment group. Group allocation was done by telephone to the Istituto Mario Negri in Bergamo. The randomisation list was generated by computer. Separate randomisation lists were used for each centre and type of hypertension.	Two ultrasound examinations (before 20 weeks of gestation and between 28 and 34 weeks) were performed to check fetal growth. The clinical data were collected prospectively during pregnancy and were sent to the coordinating centre, together with the outcome of pregnancy and the infant’s condition.	No adjustment. Randomisation. Exclusion of women history of chronic diseases such as diabetes or renal disease, documented fetal malformations, antihypertensive treatment if not interrupted before the eighth week of gestation.
Sorensen - Calcium blockers, 2001	case control	Drug intake was recorded if stated in the self- administered questionnaires (immediately after notification) and/or reported by the perinatal care physician in the personal prenatal care logbook.	Notification of malformed offspring is compulsory for physicians and there are three main sources: 1) obstetricians, 2) pediatricians (who work in the neonatal units, obstetric clinics) and 3) consultants at six prenatal diagnostic centers where severe fetal defects are diagnosed.	Controls matched to every index case according to sex, date of birth (week), and district of the parents’ residence. Adjusted for confounding factors (maternal age, maternal disease, birth order, and intake of other drugs) in conditional logistic regression analyses.
Su - Calcium blockers (Controls unexposed, disease free), 2013	population based cohort retrospective	Data on anti-hypertensive drugs use come from the National Health Insurance Research Dataset (NHIRD), which consisted of all claims data during pregnancy.	The birth certificate registry, obtained from the Department of Health in Taiwan, that contains birthdates, as well as details on gestational weeks at birth and birth weight.	No adjustment for this group of comparison. Singletons only.
Su - Calcium blockers (Controls unexposed, sick), 2013	population based cohort retrospective	Data on anti-hypertensive drugs use come from the National Health Insurance Research Dataset (NHIRD), which consisted of all claims data during pregnancy.	The birth certificate registry, obtained from the Department of Health in Taiwan, that contains birthdates, as well as details on gestational weeks at birth and birth weight.	Adjusted for the mother’s parity, maternal age, education level, diabetes, anemia, coronary heart disease, and hyperlipidemia. Singletons only.
Van Gelder - Calcium blockers, 2015	case control	Within 6 months after delivery, trained research nurses interviewed the mothers of case and control infants by telephone, in English or Spanish, about details of medication use in the 2 months before pregnancy until the end of pregnancy.	Cases and controls identified through birth defects registries (Massachusetts and parts of New York State) or from participating hospitals in the areas surrounding Boston (MA), Philadelphia (PA), San Diego (CA), and Toronto (Canada).	No adjustment. Exclusion of multiple births. Sensitivity analysis excluding infants who had a first-degree relative with the birth defects of interest.
Van Zutphen - Calcium blockers, 2014	case control	Antihypertensive medication use were collected by trained interviewers who conducted maternal telephone interviews within 24 months of delivery.	Data were abstracted from medical record, birth certificates or hospital discharge records. To confirm cases, clinical geneticists reviewed data, including consultations (urology, endocrinology, and genetic), reports (operative, pathology, and autopsy), and radiographic results.	Adjusted for site, maternal age, race and ethnicity, parity, fertility treatment, prepregnancy diabetes, gestational diabetes, and multiple birth.
Vasilakis-Scaramozza - Calcium blockers, 2013	retrospective cohort	Data were extracted from standardized clinical records for every patient within a general medical practice. These records describe notably prescribed drugs from each clinical visit.	Data were extracted from standardized clinical records for every patient within a general medical practice, including notably medical diagnoses, using ICD 9. Previous studies determined that all congenital anomalies noted in the clinical records were recorded in the computerized medical record.	Each exposed woman was matched on age, year of pregnancy outcome, and general practice with two unexposed women. Potential confounders evaluated: prepregnancy body mass index (BMI), maternal age, smoking status, history of diabetes, insulin use, exposure to a known teratogen during the first trimester, history of infertility (including use of infertility drugs), and premature delivery.
Weber-Schoendorfer - Calcium blockers, 2008	prospective cohort	A similarly structured questionnaire was used by all the centres to record the following data at the first contact during (early) pregnancy before the pregnancy outcome was known, including details of drug exposure (timing in pregnancy, dose, and duration).	Follow-up was conducted by mailed questionnaire or by a telephone interview with the woman and/or her physician and/or the pediatrician of the infant. Pregnancy outcome, gestational age at birth, birth weight, birth defects and postnatal disorders were obtained.	Outcome parameters were adjusted for maternal age, concomitant medication, alcohol and cigarette consumption, previous miscarriage and birth defects in previous offspring.
Wide-Swensson - Isradipine, 1995	randomized controlled trial	The patients were randomized by numbers. The randomization was done in blocks of 6 patients. Information as to which treatment each woman was given was stored in a sealed envelope, which was not opened until the study was completed.	Not specified. Fetal heart rate was recorded by antenatal cardiotocography performed in a quiet room before the antihypertensive treatment was commenced and at every visit.	No adjustment. Randomisation. The women were not to have any drug abuse or ingestion (within 3 months) of medications known to be toxic to major organ systems.
Zarante - Nifedipine, 2009	case control	Information collected in 10 Colombian hospitals (NOS).	Information collected in 10 Colombian hospitals (NOS).	No match/adjustment for this group of exposure. No significant differences between both groups in terms of maternal age, birth weight and gestational age.

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