- Medication and Pregnancy KB

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Abd Rahman, 2020	retrospective cohort	The data collected included drugs used prior to pregnancy and patients were classified based on their hydroxychloroquine use during pregnancy (Not Otherwise Specified).	The data collected included the antenatal complications and pregnancy outcomes (Not Otherwise Specified).	For preeclampsia: multivariate model incorporating potential confounders as covariates: maternal age, concurrent medical illness, immunosuppressive treatment, and lupus nephritis.
Al Arfaj, 2010	retrospective cohort	Treatments were recorded from medical charts.	Pregnancy data, its outcome and therapy were recorded from medical charts.	None.
Andersson (Controls exposed to corticosteroides), 2021	population based cohort retrospective	Information on prescription drug use was obtained through the Registry of Medicinal Product Statistics, which holds information on all redeemed prescriptions from all Danish pharmacies.	Outcomes obtained via the Medical Birth Registry, the Danish National Patient Registry and the Danish Civil Registration System and Statistics Denmark.	Propensity score matching for age at pregnancy, place of birth, marital status, region of residence, income, education level, year of pregnancy, parity, multiple birth pregnancy, smoking during pregnancy, previous pregnancy with the same outcome, prescription drug use in past year and hospital care utilization in past year.
Andersson (Controls unexposed, NOS), 2021	population based cohort retrospective	Information on prescription drug use was obtained through the Registry of Medicinal Product Statistics, which holds information on all redeemed prescriptions from all Danish pharmacies.	Outcomes obtained via the Medical Birth Registry, the Danish National Patient Registry and the Danish Civil Registration System and Statistics Denmark.	Propensity score matching for age at pregnancy, place of birth, marital status, region of residence, income, education level, year of pregnancy, parity, multiple birth pregnancy, smoking during pregnancy, previous pregnancy with the same outcome, prescription drug use in past year and hospital care utilization in past year.
Andreoli, 2022	nested case control	Interviews conducted retrospectively, by means of a maternal self-reported questionnaire.	Children’s follow-up made with a maternal self-reported questionnaire. Children’s diagnoses of Autoimmune diseases (AD) and/or neurodevelopmental disorders (ND) reported by the mothers were checked through a 2nd round of interview, and only cases certified by a medical specialist were considered.	None. No statistical difference in terms of preterm birth, children sex, maternal diagnosis.
Baalbaki, 2020	retrospective cohort	Individual maternal and neonatal medical records were reviewed, and data were abstracted and entered into a constructed database. Duration of medication use was collected.	Individual maternal and neonatal medical records were reviewed. Delivery characteristics were identified. The neonatal diagnosis is considered if the diagnosis was included in the infant’s discharge summary and documented by neonatologists.	Mean body mass index, drug uses, alcohol use, rates of chronic hypertension, and rates of diabetes mellitus were not significantly different between the 2 groups. Patients with multifetal gestations and prenatally diagnosed congenital anomalies were excluded. Multivariate adjustment for Maternal disease-related hospitalization during pregnancy (not indexed outcome).
Bérard, 2021	nested case control	The study medication prescription fillings were identified from the Quebec prescription drug insurance database (prescribed over- the-counter medications were also included), using timing of exposure determined by the dispensed date and duration of treatment.	The Régie de l’assurance maladie du Québec (RAMQ): diagnoses, medical procedures, socio-economic status. The Quebec birth certificates database (ISQ): patient socio-demographics, gestational age, birth weight). The MedEcho: in-hospital diagnoses and procedures, gestational age.	Multivariate adjustment, including maternal age, maternal chronic comorbidities (including diabetes, asthma, thyroid disorders), health care utilization, folic acid use, previous pregnancy (spontaneous or planned abortion, delivery) in the year before, the indications of the studied medications,... Singletons only. Exclusion of pregnancies exposed to known teratogens.
Braga, 2021	nested case control	Before conception, hydroxychloroquine was introduced when possible (Not Otherwise Specified).	Maternal and fetal outcomes were assessed (Not Otherwise Specified).	None.
Buchanan, 1996	retrospective cohort	Medical records (dose of hydroxychloroquine and duration of exposure in pregnancy).	Medical records.	None.
Canti, 2021	prospective cohort	Patients were then monitored with regular visits every month from preconception counseling to delivery and post-partum.	Serial obstetric ultrasound to monitor fetal growth and uterine arteries doppler were also per- formed at each visit and associated findings recorded.	No adjustment, except for Intrauterine growth retardation: multivariate analysis (AZA, aPL). The 2 groups of patients did not differ at baseline in terms of demographic and clinical characteristics (maternal age, hypertension, thyroid disease) and obstetric history (early and late miscarriage, intrauterine deaths, preterm, preeclampsia, pathologic obstetric history).
Chakravarty, 2005	retrospective cohort	Review of the medical records. At each prenatal visit, data were abstracted regarding changes in medications.	Review of the medical records. All data abstraction was done by a single investigator, and questions were handled by consensus of the group.	None.
Chambers (Controls unexposed, disease free), 2022	prospective cohort	Women enrolled in the study completed up to 3 prenatal interviews. Interviewers captured the following detailed information: all prescription and over-the-counter medications, including dosages, dates, and indications. Information on exposures was abstracted also from medical records.	Enrolled women completed 1 postnatal telephone interview. They were asked to release medical records from their physicians. Information on pregnancy and newborn outcomes was abstracted from these records. Participants were offered a specialized physical examination (blinded to mother’s exposures).	Adjusted/exclusion for multiple pregnancy. No statistical difference between the 2 groups for pre‐pregnancy BMI ; previous outcome (birth defect, spontaneous abortion, preterm), ethnicity, IVF with current pregnancy, alcohol and tobacco use during pregnancy.
Chambers (Controls unexposed, sick), 2022	prospective cohort	Women enrolled in the study completed up to 3 prenatal interviews. Interviewers captured the following detailed information: all prescription and over-the-counter medications, including dosages, dates, and indications. Information on exposures was abstracted also from medical records.	Enrolled women completed 1 postnatal telephone interview. They were asked to release medical records from their physicians. Information on pregnancy and newborn outcomes was abstracted from these records. Participants were offered a specialized physical examination (blinded to mother’s exposures).	Adjusted/exclusion for multiple pregnancy. Matched for disease category. No statistical difference between the 2 groups for pre‐pregnancy BMI ; previous outcome (birth defect, spontaneous abortion, preterm), ethnicity, IVF with current pregnancy, alcohol and tobacco use during pregnancy, prednisone and/or systemic oral glucocorticoid, maternal comorbidities (including pregestational hypertension).
Cimaz, 2007	retrospective cohort	Not specified.	Status of vaccination was confirmed by health certificates, which in Italy are automatically registered in a computerized system after each immunization. Whole blood were collected after the usual cycle of vaccination.	None.
Clowse, 2006	prospective cohort	At the first visit, the patient’s lupus and obstetric history and medications taken prior to and during pregnancy were recorded. At each subsequent visit, generally every 4–6 weeks throughout pregnancy, medications were recorded.	Pregnancy outcomes were obtained through obstetric documentation.	None.
Colvin, 2010	retrospective cohort (claims database)	The national Pharmaceutical Benefits Scheme, with around 80% of prescriptions dispensed in Australia.	Health administrative data from the WA Hospital Morbidity Data System, the Midwives’ Notification System, the WA Registry of Births and Deaths and the Birth Defect Registry of WA, enabling pregnancies and pregnancy outcomes to be ascertained.	None.
Cooper (controls exposed to TNF-I), 2014	retrospective cohort (claims database)	The Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases.	Outcomes were identified from vital records and medical records: birth certificate check-boxes, infant claims data, fetal death or death certificates, records of maternal hospitalization. Medical records and autopsy reports were reviewed to confirm all adverse fetal outcomes.	No adjustment for this group of comparison.
Cooper (controls unexposed, sick), 2014	retrospective cohort (claims database)	The Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases.	Outcomes were identified from vital records and medical records: birth certificate check-boxes, infant claims data, fetal death or death certificates, records of maternal hospitalization. Medical records and autopsy reports were reviewed to confirm all adverse fetal outcomes.	Propensity score including maternal age, race, ethnicity, years of education, parity, chronic health diagnoses (smoking, diabetes, epilepsy, asthma, renal disease, cancer, heart disease, hypertension, HIV, substance use, obesity, headaches), medications for chronic diseases, chronic immune mediated diseases... Singletons only. Exclusion of births with exposure to teratogenic medications.
Costedoat-Chalumeau, 2003	prospective cohort	Pregnancies who received treatment in the author's hospital (not otherwise specified).	Pediatric cardiologists (blinded to maternal treatment) measured the PR and corrected QT (QTc) intervals for all children in whom electrocardiography was performed. Data on the child health were gathered from the mothers (or general practitioners or pediatricians when women were lost to followup).	None.
Diav-Citrin, 2013	prospective cohort	Details of exposure were collected during pregnancy, at the initial contact to the TIS and before pregnancy outcome was known, using a structured questionnaire. After delivery, HCQ and other exposures were ascertained.	After the expected date of delivery, pregnancy outcome was actively sought after. Follow-up was conducted by a telephone interview with the woman to obtain details on the pregnancy outcome, gestational age at delivery, birth weight, congenital anomalies and neonatal complications.	None (only the OR for miscarriages was adjusted, without other details). There were no significant differences between the groups in maternal age or distribution of cigarette smokers.
Do, 2020	retrospective cohort	By medical chart review, exposure was based on mention in physician notes in the medication list or plan at the earliest prenatal visit.	Outcomes were abstracted during medical chart review.	Adjusted for Maternal age and propensity score adjusted (based on race, body mass index, smoking, renal complication, renal history, antiphospholipid syndrome/ antiphospholipid antibody positivity).
Frassi, 2004	prospective cohort	Not specified	Not specified	None
Gernaat (Controls unexposed, disease free), 2022	population based cohort retrospective	The nationwide Prescribed Drug Register (PDR) includes all pharmacy-dispensed prescription medications.	Gestational Diabetes Mellitus (GDM) was identified using ≥ 1ICD-coded visit (ICD-10: O24.4) in the in- or outpatient records of the National Patient Register (NPR) and Medical Birth Register (MBR).	No match, no adjustment for this comparison (hydroxychloroquine versus no hydroxychloroquine). Singleton only. Exclusion of women with pregestational Diabetes Mellitus as they should not receive a diagnosis of Gestational Diabetes Mellitus (GDM).
Gernaat (Controls unexposed, sick), 2022	population based cohort retrospective	The nationwide Prescribed Drug Register (PDR) includes all pharmacy-dispensed prescription medications.	Gestational Diabetes Mellitus (GDM) was identified using ≥ 1ICD-coded visit (ICD-10: O24.4) in the in- or outpatient records of the National Patient Register (NPR) and Medical Birth Register (MBR).	No match, no adjustment for this comparison (hydroxychloroquine versus no hydroxychloroquine). Singleton only. Exclusion of women with pregestational Diabetes Mellitus as they should not receive a diagnosis of Gestational Diabetes Mellitus (GDM).
Haase, 2020	prospective cohort	Not specified.	Not specified.	A multiple logistic regression was performed with adjustment for confounding factors (Not Otherwise Specified). Singleton pregnancies only.
Haase, 2021	prospective cohort	Not specified.	Not specified.	Adjustment for age, Body mass index, hypertension, disease activity in 1st trimester, lupus nephritis, nulliparity, history of preeclampsia and high- risk anti-phospholipid (aPL) profile.
He, 2022	nested case control	The therapeutic data before and after pregnancy in both TAK patients and controls were collected and analyzed (Not Otherwise Specified).	The demographic, laboratory, imaging, and therapeutic data before and after pregnancy in both TAK patients and controls were collected and analyzed (Not Otherwise Specified).	No match/adjustment for analysis of medicines during pregnancy. Patients with a history of uterine surgery and subjects with pregnancies through assisted reproductive technology or multiple pregnancies were excluded.
Howley - BDS study, 2021	case control	Women were asked about medications taken. Data were maternal self-reported up to 6 months after delivery via in-person interviews.	Review of discharge records or registry data at participating hospitals or birth defect registries.	None.
Howley - NBDPS study, 2021	case control	Women were asked about medications taken. Data were maternal self-reported up to 24 months after delivery via computer-assisted telephone interviews.	Cases were ascertained through birth defects surveillance programs in 10 states (Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah). Clinical geneticists reviewed cases to determine eligibility for the overall study and to classify cases.	None.
Howren, 2020	retrospective cohort (claims database)	PharmaNet captures complete information on all drug prescriptions dispensed including drug identification number, dispensation date, dispensation quantity, dosage, and duration.	Data from the Medical Services Plan database (MSP), the hospital admissions in the Discharge Abstract Database (DAD) and the BC Perinatal Database Registry (BCPDR) which contains data from obstetrical and neonatal medical records on ~99% of births in BC.	Multivariate model. Potential confounders considered: maternal and pregnancy characteristics (BMI, age, prior. adverse pregnancy outcome...), maternal comorbidities (anxiety, depression, diabetes), other medication use before pregnancy and during pregnancy, and healthcare utilisation (considered markers of disease severity and health status).
Huybrechts (Controls unexposed, NOS), 2021	retrospective cohort (claims database)	Database of prescriptions filled on an outpatient basis.	The presence of malformations was defined using validated algorithms based on inpatient or outpatient diagnoses and procedures, which have been shown to identify the outcomeswith high specificity;	No adjustment for this group of comparison. Exclusion of pregnancies exposed to known teratogens.
Huybrechts (Controls unexposed, sick), 2021	retrospective cohort (claims database)	Database of prescriptions filled on an outpatient basis.	The presence of malformations was defined using validated algorithms based on inpatient or outpatient diagnoses and procedures, which have been shown to identify the outcomeswith high specificity;	Proxies and potential confounders included maternal age, race and ethnicity, autoimmune rheumatic disorders other maternal conditions (eg, diabetes, hypertension, psychiatric conditions, renal disease, neurologic conditions, ...), concomitant medication use (NSAIDs, DMARDs, systemic steroids, ..) and general markers of the burden of illness. Exclusion of pregnancies exposed to known teratogens.
Kiatkongchuchai, 2020	nested case control	Current medication used were collected (Not Otherwise Specified).	Not specified.	None.
Kroese, 2017	retrospective cohort	Data were retrieved from patient medical files, from an intern systemic lupus erythematosus (SLE) registry, and from an in-house obstetric registry.	Data were retrieved from patient medical files, from an intern systemic lupus erythematosus (SLE) registry, and from an in-house obstetric registry.	All analyses were adjusted for antiphospholipid anti- body (aPL) status except for early spontaneous abortion, for which aPL occurrence was too infrequent for analysis.
Langen, 2014	retrospective cohort	Data were collected from review of medical records and included medication use.	Data were collected from review of medical records and included pregnancy outcomes.	None.
Leroux, 2015	retrospective cohort	Reviewing of medical records for identification of medication exposures administered before, during the pregnancy, and postpartum.	Reviewing of medical records to collect maternal, fetal and neonatal outcomes and the mode of delivery.	None. No statistical difference of maternal age, Body mass index, Parity, ...
Levy, 2001	randomized controlled trial	Patients were randomized to receive Hydroxychloroquine (HCQ) or placebo during pregnancy. HCQ or identical placebo capsules were dispensed and replaced at subsequent visits until 12 weeks after delivery.	Each baby was carefully examined in the neonatal period by a skilled pediatrician or specialist blinded to use of HCQ during pregnancy.	No adjustment. Randomisation.
Liu, 2021	retrospective cohort	The hospital’s electronic medical discharge reports were used. Medication exposures were collected.	The hospital’s electronic medical discharge reports were used. Preeclampsia and other pregnancy outcomes were analyzed.	Propensity score matching (PSM) on the factors that were significantly different between those two group (maternal age, glucocorticoid use, the use of immunosuppressor). No difference between the 2 groups for history of fetal loss, gestational diabete mellitus, twin pregnancy, parity...
Louthrenoo, 2021	retrospective cohort	Review of the medical records.	Review of the medical records.	None.
Mollerach, 2019	retrospective cohort	Review of electronic medical records of patients.	Review of outpatient medical records, hospitalizations, and all cardiac ultrasounds performed during pregnancy follow-up.	None.
Moroni, 2016	prospective cohort	Data about history and therapy of Systemic Lupus Erythematosus (SLE), lupus nephritis were recorded from medical records. Women were seen at least once a month up to the 24th week of gestation and every two weeks from the 24th week up to delivery.	Newborn weight and Apgar index to summarize the health of newborns were regularly collected.	None.
Placais, 2019	case control	Not specified.	Not specified.	Multivariate analysis (age, treatments, Sjögren syndrome, Placental intervillitis).
Poh, 2020	retrospective cohort	Not specified.	Maternal and fetal outcomes were reviewed/evaluated (Not Otherwise Specified).	None.
Reynolds, 2022	retrospective cohort	Retrospective data were collected using a previously piloted questionnaire, completed by women and by collection of maternal data via interview and reviewing the medical records. Pregnancy data collected included drug exposure at conception, during pregnancy, and during breastfeeding.	Retrospective data were collected using a previously piloted questionnaire. First part: completed by women and reviewing the medical records. A second part of the questionnaire was completed by the mother to collect data on outcomes in each child up to the age of 17 (malfo, infections...).	No adjustment.
Seo, 2019	retrospective cohort	Retrospective study (probably medical records, not clearly specified).	Retrospective study (probably medical records, not clearly specified).	Preeclampsia: multiple logistic analysis adjusting for body mass index (BMI), lupus nephritis, serum uric acid, and estimated glomerular filtration rate. Singleton only. No difference of maternal age, history of spontaneous abortion, multiparous.
Tang, 2022	retrospective cohort	Review of medical records from the IgA nephropathy registration database at Peking University First Hospital. Utilization of Hydroxycloroquine during pregnancy was identified using prescription records of Hydroxycloroquine dispensing any time during pregnancy.	Review of medical records from the IgA nephropathy registration database at Peking University First Hospital.	No adjustment. Singleton only. There was no significant difference in age at pregnancy between the two groups.
Tincani, 2005	prospective cohort	Not specified	Not specified	None
Viktil (Controls exposed to other treatments), 2012	population based cohort propective	Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).	The Medical Birth Registry of Norway (MBRN), a population based register that contains information about all births, including late abortion, from 12 weeks of gestation onwards.	None for this group of exposure. Singletons only.
Viktil (Controls unexposed, NOS), 2012	population based cohort propective	Prescriptions were recorded from 3 months prior to conception until labour from the Norwegian Prescription Database (NorPD).	The Medical Birth Registry of Norway (MBRN), a population based register that contains information about all births, including late abortion, from 12 weeks of gestation onwards.	None for this group of exposure. Singletons only.
Vroom (controls exposed to sulfasalazine), 2009	retrospective cohort (claims database)	Prescription database, the General Practice Research Database (GPRD).	Pregnancy outcomes were determined from the General Practice Research Database (GPRD).	Adjusted for alcohol use and smoking habits and maternal age.
Vroom (controls unexposed, disease free), 2009	retrospective cohort (claims database)	Prescription database, the General Practice Research Database (GPRD).	Pregnancy outcomes were determined from the General Practice Research Database (GPRD).	Adjusted for alcohol use and smoking habits and maternal age.
Zhang, 2022	nested case control	Using the hospital electronic database, the medical records of patients were comprehensively reviewed to collect the type of current medications.	Using the hospital electronic database, the medical records of patients were comprehensively reviewed to collect clinical information (pregnancy and neonatal outcomes).	Adjusting for age. Singletons only.

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