- Medication and Pregnancy KB

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bérard, 2012	nested case control	From the Régie de l’assurance maladie du Québec (RAMQ), for each pregnant woman, it was obtained data on all filled prescriptions in the year preceding and during pregnancy including date of filling, name, dosage, form, quantity, and duration.	MED-ECHO provided data on all maternal and baby acute care hospitalizations in the year prior, during pregnancy, and in the year after pregnancy. The ISQ provided also baby characteristics (gender, birth weight, gestational age at delivery).	Controls matched on index date and gestational age. Considered potential confounding variables: (1) maternal sociodemographic characteristics on the first day of gestation (maternal age, welfare status, area of resi- dence [rural/urban]); (2) pregnancy-related variables (gestational age at index date); and (3) maternal chronic conditions
De Jonge - Sumatriptan, 2013	case control	A population-based prescription database, the IADB was used to obtain the mother’s pharmacy records. Actual use of the prescribed medication is verified in a telephone interview and only the actually used medication is registered.	Information on congenital malformations is obtained from the medical files, including pathology reports, and coded afterwards.	None
Harris (Control exposed before pregnancy), 2018	prospective cohort	Follow-up is conducted via questionnaires in pregnancy weeks 17, 22, and 30. Medication use in pregnancy was reported in Q1 (6 months pre- pregnancy and gestational weeks 0-13 ), Q3 (week 13-29 ), and Q4 (week 30-end of pregnancy) for specific indications.	Administration by the mother of a short version of the Child Behaviour Checklist (CBCL), the communication domain of the Ages and Stages Questionnaire (ASQ) and a short version of the Emotionality Activity and Shyness Temperament Questionnaire (EAS).	Adjusted estimates are weighted according to propensity score-based methods with inverse probability of treatment weights (IPTW)
Harris (Control mainly exposed to other treatments, sick), 2018	prospective cohort	Follow-up is conducted via questionnaires in pregnancy weeks 17, 22, and 30. Medication use in pregnancy was reported in Q1 (6 months pre- pregnancy and gestational weeks 0-13 ), Q3 (week 13-29 ), and Q4 (week 30-end of pregnancy) for specific indications.	Administration by the mother of a short version of the Child Behaviour Checklist (CBCL), the communication domain of the Ages and Stages Questionnaire (ASQ) and a short version of the Emotionality Activity and Shyness Temperament Questionnaire (EAS).	Adjusted estimates are weighted according to propensity score-based methods with inverse probability of treatment weights (IPTW)
Källén (control exposed to ergots), 2011	population based cohort propective	Pregnant women who attend antenatal clinics in Sweden (which the vast majority do) are interviewed by a midwife and asked about drugs used since the pregnancy started. This interview is usually made before the end of the first trimester (usually between weeks 10 and 12 of pregnancy).	The outcomes were ascertained from multiple sources: the paediatric form of the Medical Birth Register, the Register of Birth Defects and the Patient Register.	No adjustment for this control group.
Källén (control unexposed, disease free), 2011	population based cohort propective	Pregnant women who attend antenatal clinics in Sweden (which the vast majority do) are interviewed by a midwife and asked about drugs used since the pregnancy started. This interview is usually made before the end of the first trimester (usually between weeks 10 and 12 of pregnancy).	The outcomes were ascertained from multiple sources: the paediatric form of the Medical Birth Register, the Register of Birth Defects and the Patient Register.	Adjustment for confounders of interest: year of delivery, maternal age, parity, maternal smoking and BMI.
Kallen - Sumatriptan, 2001	population based cohort retrospective	The register is based on information obtained by interview at the first antenatal visit (usually around 10 to 12 weeks gestation). Information on drug use is, thus, based on an interview at the first antenatal visit with a midwife.	Outcomes were registered in the Medical Birth Registry, based on data collected at delivery and at the pediatric examination of the newborn, using standardized forms.	None
Nezvalová-Henriksen (Control unexposed, disease free), 2013	population based cohort retrospective	The Norwegian Prescription Database (NorPD) was the source of information on the individual triptan prescriptions. The timing of triptan redemption, in gestational weeks, was determined by the number of weeks from the onset of pregnancy to the date the prescription was redeemed.	The medical birth registry of Norway where data are collected via obligatory standardised forms by trained health personnel during medical check-ups during pregnancy and during the delivery and the subsequent hospital stay.	The confounding factors included, among others, maternal age, pregnancy complications, prescribed poten- tially teratogenic drugs during pregnancy, other co-medication during pregnancy, and for some outcomes delivery complications
Nezvalová-Henriksen (Control unexposed, sick), 2013	population based cohort retrospective	The Norwegian Prescription Database (NorPD) was the source of information on the individual triptan prescriptions. The timing of triptan redemption, in gestational weeks, was determined by the number of weeks from the onset of pregnancy to the date the prescription was redeemed.	The medical birth registry of Norway where data are collected via obligatory standardised forms by trained health personnel during medical check-ups during pregnancy and during the delivery and the subsequent hospital stay.	No adjustment for this control group.
O'Quinn - Sumatriptan, 1999	prospective cohort	The study was designed to include four office visits. Telephone interviews and automated prescription refilling occurred in between visits. Patients were asked to injected sumatriptan with an auto-injector. Diary cards were also used to record sumatriptan injections, concomitant drug use...	All pregnancies were followed to outcome in the perinatal period. Investigators were required to report the name of the patient’s obstetrician in order that follow-up could be accomplished.	None
Olesen - Sumatriptan (Control unexposed, disease free), 2000	retrospective cohort (claims database)	The North Jutland County’s prescription data base	The Danish Medical Birth Registry includes data on all births since 1973, including each child’s birth- day, gestational age, birth weight, and malformations. Abortions are not recorded in the registry. The data stem from official reports filled in by the midwives at- tending deliveries.	Odds ratios were adjusted for the mother’s smoking during pregnancy (yes or no), parity (number of primiparous women), maternal age, and marital status (the number of women who lived with the child’s father).
Olesen - Sumatriptan (Control unexposed, sick), 2000	retrospective cohort (claims database)	The North Jutland County’s prescription data base	The Danish Medical Birth Registry includes data on all births since 1973, including each child’s birth- day, gestational age, birth weight, and malformations. Abortions are not recorded in the registry. The data stem from official reports filled in by the midwives at- tending deliveries.	Odds ratios were adjusted for the mother’s smoking during pregnancy (yes or no), parity (number of primiparous women), maternal age, and marital status (the number of women who lived with the child’s father).
Shuhaiber - Sumatriptan (Control exposed to other treatments), 1998	prospective cohort	Pregnant women contacted a teratogen information service (TIS) during pregnancy to request counseling after sumatriptan use.	All patients were contacted by telephone within 2 years of the expected date of confinement and asked details about the outcome of pregnancy, birth weight, birth defects, and complications. One center (Motherisk) also requested written documentation from the child’s physician.	None
Shuhaiber - Sumatriptan (Control unexposed, disease free), 1998	prospective cohort	Pregnant women contacted a teratogen information service (TIS) during pregnancy to request counseling after sumatriptan use.	All patients were contacted by telephone within 2 years of the expected date of confinement and asked details about the outcome of pregnancy, birth weight, birth defects, and complications. One center (Motherisk) also requested written documentation from the child’s physician.	None
Spielmann (Control mainly exposed other treatments, sick), 2017	prospective cohort	All data are recorded using structured questionnaires via phone interview and/or as a written form.	Structured questionnaire administered via phone interview and/or as a written form, notably on gestational age at birth, weight, length, head circumference, Apgar score, umbilical artery pH, birth defects, postnatal disorders, pregnancy loss. Medical reports requested in cases of birth defects.	The propensity score (PS) was estimated using boosted regression trees on the basis of the following covariates: Maternal age, body mass index, smoking habits, alcohol consumption, number of previous abortions and previous pari- ties, as well as number of previous children with birth defects
Spielmann (Control unexposed, disease free), 2017	prospective cohort	All data are recorded using structured questionnaires via phone interview and/or as a written form.	Structured questionnaire administered via phone interview and/or as a written form, notably on gestational age at birth, weight, length, head circumference, Apgar score, umbilical artery pH, birth defects, postnatal disorders, pregnancy loss. Medical reports requested in cases of birth defects.	The propensity score (PS) was estimated using boosted regression trees on the basis of the following covariates: Maternal age, body mass index, smoking habits, alcohol consumption, number of previous abortions and previous pari- ties, as well as number of previous children with birth defects
Werler, 2009	case control	Mothers of case- and control-infants are interviewed by telephone within 24 months after their estimated date of delivery, notably about pregnancy exposures.	In each of the 10 states, birth defect registries identify infants with selected major structural malformations and a random sample of live born infants without major defects as a control group. Diagnoses abstracted from medical records were reviewed by a clinical geneticist.	Controls were matched to cases by mother’s year of age at delivery and state. adjusted for maternal age at delivery and state of residence by stratification and for race/ethnicity, BMI, education, alcohol use, oral contraceptive use, folic acid supplementation.
Wood 2016a (Control exposed only before pregnancy), 2016	prospective cohort	Medication information was gathered from two prenatal (Q1, Q3) and one postpartum questionnaire (Q4); this information was reported before the outcome was known.	Administration by the mother of a short version of the Child Behaviour Checklist (CBCL), a validated, parent-reported measure of child behavior widely used in both clinical and research practice.	Multivariate adjustment: Maternal age, pre-pregnancy BMI, education, marital status, parity, smoking, alcohol use, other medications (psychotropic medications, including antidepressants, benzodiazepines, and antiepileptics) and maternal symptoms of depression and anxiety.
Wood 2016a (Control mainly exposed to other treatments, sick), 2016	prospective cohort	Medication information was gathered from two prenatal (Q1, Q3) and one postpartum questionnaire (Q4); this information was reported before the outcome was known.	Administration by the mother of a short version of the Child Behaviour Checklist (CBCL), a validated, parent-reported measure of child behavior widely used in both clinical and research practice.	Multivariate adjustment: Maternal age, pre-pregnancy BMI, education, marital status, parity, smoking, alcohol use, other medications (psychotropic medications, including antidepressants, benzodiazepines, and antiepileptics) and maternal symptoms of depression and anxiety.
Wood 2016a (Control unexposed, disease free), 2016	prospective cohort	Medication information was gathered from two prenatal (Q1, Q3) and one postpartum questionnaire (Q4); this information was reported before the outcome was known.	Administration by the mother of a short version of the Child Behaviour Checklist (CBCL), a validated, parent-reported measure of child behavior widely used in both clinical and research practice.	Multivariate adjustment: Maternal age, pre-pregnancy BMI, education, marital status, parity, smoking, alcohol use, other medications (psychotropic medications, including antidepressants, benzodiazepines, and antiepileptics) and maternal symptoms of depression and anxiety.
Wood 2016b, 2016	prospective cohort	Medication information was gathered prospectively from two prenatal (Q1, Q3) and one postpartum questionnaire (Q4).	Administration by the mother of a short version of the Emotionality, Activity, and Shyness Temperament Questionnaire (EAS) and of the abbreviated Ages and Stages Questionnaire (ASQ).	At least: age, pre-pregnancy BMI, marital status, education, smoking or alcohol use during pregnancy, depression, use of triptans prior to pregnancy, and concomitant medication use during pregnancy.

master protocol