- Medication and Pregnancy KB

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Andersen 2017 (control exposed to MMI/CMZ), 2017	population based cohort retrospective	Information on maternal use of ATDs was obtained from the Swedish Prescribed Drug Register (SPDR) which holds data on all prescriptions drugs in Swedish since 2005.	The Swedish Medical Birth Registry provided child characteristics (gender, gestational age at birth, birth weight, mode of delivery). Diagnoses of birth defects in the children were obtainedfrom the Swedish National Patient Register.	No adjustment for the control group exposed to MMI/CMZ.
Andersen 2017 (control unexposed, disease free), 2017	population based cohort retrospective	Information on maternal use of ATDs was obtained from the Swedish Prescribed Drug Register (SPDR) which holds data on all prescriptions drugs in Swedish since 2005.	The Swedish Medical Birth Registry provided child characteristics (gender, gestational age at birth, birth weight, mode of delivery). Diagnoses of birth defects in the children were obtained from the Swedish National Patient Register.	The adjusted model included birth year of the child, maternal age, parity, type of pregnancy, body mass index, smoking and origin as categorical variables. Additional adjustment for maternal comorbidities (diabete, epilespy) as well as deviations in birth weight, gestational age at birth and mode of delivery did not change figures.
Andersen 2017 (control unexposed, sick), 2017	population based cohort retrospective	Information on maternal use of ATDs was obtained from the Swedish Prescribed Drug Register (SPDR) which holds data on all prescriptions drugs in Swedish since 2005.	The Swedish Medical Birth Registry provided child characteristics (gender, gestational age at birth, birth weight, mode of delivery). Diagnoses of birth defects in the children were obtainedfrom the Swedish National Patient Register.	No adjustment for the control group unexposed, sick.
Andersen 2019 (control exposed to MMI/CMZ), 2019	population based cohort retrospective	The Danish National Prescription Register (DNPR) includes information on redeemed prescriptions of drugs coded according to the Anatomical Therapeutical Classification (ATC) system, and drugs used for the treatment of thyroid disease are included in the ATC group: H03.	Information on birth defects in the child was assessed from in- and outpatient hospital diagnoses in the Danish National Hospital Register (DNHR) (16) coded according to the 10th International Classification of Disease (ICD-10).	Not adjustment for this control group.
Andersen 2019 (control unexposed, disease free), 2019	population based cohort retrospective	The Danish National Prescription Register (DNPR) includes information on redeemed prescriptions of drugs coded according to the Anatomical Therapeutical Classification (ATC) system, and drugs used for the treatment of thyroid disease are included in the ATC group: H03.	Information on birth defects in the child was assessed from in- and outpatient hospital diagnoses in the Danish National Hospital Register (DNHR) (16) coded according to the 10th International Classification of Disease (ICD-10).	Adjusted for maternal age, parity, multiple birth, origin, diabetes, and smoking.
Banhidy, 2011	case control	Mothers were asked to send us the prenatal maternity logbook (obstetricians recorded maternal diseases, and related drug prescriptions in this logbook, in the first prenatal care visit was between the 6th and 12th gestational week) and other medical records particularly discharge summaries.	Diagnosis of Congenital Anomalies was based on the compulsory notification of physicians to the HCAR. Pathologists sent a copy of the autopsy report to the HCAR if defects were identified in stillbirths and infant deaths.	No adjustment for this group of comparison.
Chen (Control exposed to MMI), 2011	retrospective cohort (claims database)	Taiwan National Health Insurance Research Dataset (NHIRD) includes the cost of inpatient treatment and outpatient prescriptions.	The national birth certificate registry of Taiwan include the birth dates of both infants and parents, the gestational age of the baby at birth, birth-weight...	Women of comparison group (five per study-group woman) were matched on age.
Chen (control unexposed, disease free), 2011	retrospective cohort (claims database)	Taiwan National Health Insurance Research Dataset (NHIRD) includes the cost of inpatient treatment and outpatient prescriptions.	The national birth certificate registry of Taiwan include the birth dates of both infants and parents, the gestational age of the baby at birth, birth-weight...	Comparison group matched on maternal age.
Chen (control unexposed, sick), 2011	population based cohort retrospective	Taiwan National Health Insurance Research Dataset (NHIRD) includes the cost of inpatient treatment and outpatient prescriptions.	The national birth certificate registry of Taiwan include the birth dates of both infants and parents, the gestational age of the baby at birth, birth-weight...	Adjusted for maternal education, anaemia, hyperlipidaemia, pregestational diabetes, pregestational hypertension, hyperemesis gravidarum and infant’s gender and birth order.
Clementi, 2010	case control	Not specified. The coverage, structure, methods, and sources of ascertainment, described elsewhere, varied from program to program (12 surveillance programs included).	These data were reviewed for malformation classification by a clinician with expertise in genetics and dysmorphology to separate subjects of isolated major malformations from those of multiple congenital anomalies.	Analyses were stratified by surveillance program. Further adjustment could include covariates such as year of birth, maternal age, and parity.
Davis, 1989	prospective cohort	After treatment was begun, follow-up was scheduled at least twice monthly and medication was adjusted. All information was obtained by chart review. The management of women whose pregnancies were complicated by thyrotoxicosis was directed by one of the author.	Neonatal information was obtained from the discharge summary routinely included in the maternal record and, when possible, the neonatal record.	None
Gianetti (control exposed to MMI), 2015	retrospective cohort	Records were reviewed retrospectively in order to collect data notably on specific antithyroid drug used and its dose.	Clinical and biochemical notes, information on delivery and postpartum records were reviewed retrospectively in order to assess maternal and fetal outcomes.	None
Gianetti (control unexposed, sick), 2015	retrospective cohort	Records were reviewed retrospectively in order to collect data notably on specific antithyroid drug used and its dose.	Clinical and biochemical notes, information on delivery and postpartum records were reviewed retrospectively in order to assess maternal and fetal outcomes.	None
Hawken (control exposed to MMI), 2016	retrospective cohort	Review of the files obtained by hospitals in the region after having contacted hospitals and open-care endocrinologists working in the Poitou-Charentes region.	Review of the files obtained by hospitals in the region after having contacted hospitals and open-care endocrinologists working in the Poitou-Charentes region. We also focused on foetal monitoring (ultrasound and laboratory) and the clinical and biological characteristics of the neonate.	None
Howley, 2017	case control	Mothers reported medications taken during pregnancy, including timing, frequency, and duration of medication use.	Case information, including medical record information, was obtained from birth defects surveillance programs in 10 states. Clinical geneticists reviewed each case to determine eligibility and to classify case infants.	Adjusted odds ratios (aORs) were controlling for maternal age at delivery, race/ethnicity, and state of residence at the time of the infant’s birth. Additional covariates were also included in the models (maternal education, number of previous pregnancies, pre- pregnancy body mass index, use of any treatment for infertility, smoking, and folic acid-containing supplement use).
Korelitz (control exposed to MMI), 2013	retrospective cohort (claims database)	Prescription drug claims were used to determine ATD therapy.	In the administrative claims database, pregnancies and imputed gestational age were identified based on the diagnosis code associated with the pregnancy outcome using an algorithm.	No adjustment for this control group.
Korelitz (control exposed to MMI), 2013	retrospective cohort (claims database)	Prescription drug claims were used to determine ATD therapy.	In the administrative claims database, pregnancies and imputed gestational age were identified based on the diagnosis code associated with the pregnancy outcome using an algorithm.	No adjustment for this control group.
Korelitz (control unexposed, disease free), 2013	retrospective cohort (claims database)	Prescription drug claims were used to determine ATD therapy.	In the administrative claims database, pregnancies and imputed gestational age were identified based on the diagnosis code associated with the pregnancy outcome using an algorithm.	Odds ratios (ORs), CIs, and p-values were obtained from logistic regression models that adjusted for the mother’s age.
Korelitz (control unexposed, sick), 2013	retrospective cohort (claims database)	Prescription drug claims were used to determine ATD therapy.	In the administrative claims database, pregnancies and imputed gestational age were identified based on the diagnosis code associated with the pregnancy outcome using an algorithm.	No adjustment for this control group
Lo (control exposed to MMI), 2015	retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC) is a large integrated health care delivery system. Pharmacologic exposures were obtained from health plan electronic databases.	Kaiser Permanente Northern California (KPNC) allowed to track gestational age and weight at birth, neonatal intensive care unit (NICU) admissions, neonatal diagnoses, and outcomes. Chart review was conducted by a neonatologist (MK) to adjudicate congenital anomalies in all infants exposed to ATDs.	None for comparison with MMI
Lo (control unexposed, sick), 2015	retrospective cohort (claims database)	Kaiser Permanente Northern California (KPNC) is a large integrated health care delivery system. Pharmacologic exposures were obtained from health plan electronic databases.	Kaiser Permanente Northern California (KPNC) allowed to track gestational age and weight at birth, neonatal intensive care unit (NICU) admissions, neonatal diagnoses, and outcomes. Chart review was conducted by a neonatologist (MK) to adjudicate congenital anomalies in all infants exposed to ATDs.	None for comparison with Thyrotoxicosis but no gestational ATD group control.
Momotani (control exposed to MMI), 1997	prospective cohort	Administration of MMI or PTU by investigators.	Blood samples were obtained from the women and from the umbilical cords of their respective infants at the time of delivery. Informed consent for blood drawing was obtained from every mother who was studied.	None
Rosenfeld, 2009	prospective cohort	Details of exposure were collected during pregnancy using a structured questionnaire. Standardized data collection forms were used notably to record the following information by telephone: exposure details (dose, duration and timing of pregnancy), and concurrent exposures.	A structured questionnaire was dispensed by phone to obtain pregnancy outcome, gestational age at delivery, birth weight, major or minor birth defects and fetal or neonatal thyroid status. Verification was performed with medical documents, contact of the child’s physician...	None
Seo (control exposed to MMI), 2018	retrospective cohort (claims database)	National Health Insurance (NHI) database	All inpatient admissions and outpatient visits with a primary or additional diagnosis of congenital malformations	No adjustment for the comparison with PTU alone.
Seo (control unexposed, NOS), 2018	retrospective cohort (claims database)	National Health Insurance (NHI) database	All inpatient admissions and outpatient visits with a primary or additional diagnosis of congenital malformations	Adjustement for maternal age, birth year, multiple pregnancies, and infant sex.
Wing (control exposed to MMI), 1994	cohort	The patients were followed up prospectively during pregnancy with treatment administration.	Retrospectively, the maternal and fetal outcomes were reviewed from clinic, labor, delivery, and postpartum records.	No statistical adjustment was made for multiple end points.
Wing (control unexposed, sick), 1994	cohort	The patients were followed up prospectively during pregnancy with treatment administration.	Retrospectively, the maternal and fetal outcomes were reviewed from clinic, labor, delivery, and postpartum records.	No statistical adjustment was made for multiple end points.
Yoshihara (control exposed to MMI), 2012	retrospective cohort	Review of the medical records.	During the mothers’ 1st visit after delivery, a physician interviewed them about GA at delivery, birth weight, and the presence and type of major or minor birth defects in their infant. In case of malformation, the doctor corresponded with the gynecologist to obtain details on anomalies.	No adjustment for comparison with MMI group as control.
Yoshihara (control unexposed, sick), 2012	retrospective cohort	Review of the medical records.	During the mothers’ 1st visit after delivery, a physician interviewed them about GA at delivery, birth weight, and the presence and type of major or minor birth defects in their infant. In case of malformation, the doctor corresponded with the gynecologist to obtain details on anomalies.	Maternal age and mother’s thyroid status in the first trimester of pregnancy were also included in the models to adjust for confounding.
Yoshihara (Controls exposed to MMI), 2021	retrospective cohort	Not specified (Pregnant patients being treated at the institution were informed during their pregnancy that they would be asked about the outcome of their pregnancy after delivery).	At the first visit after delivery and 1 year after delivery, a physician interviewed mothers, with a structured questionnaire about the outcome of pregnancy, gestational age at delivery, birth weight, and the presence and type of major or minor birth defects.	None
Yoshihara (Controls unexposed, sick), 2021	retrospective cohort	Not specified (Pregnant patients being treated at the institution were informed during their pregnancy that they would be asked about the outcome of their pregnancy after delivery).	At the first visit after delivery and 1 year after delivery, a physician interviewed mothers, with a structured questionnaire about the outcome of pregnancy, gestational age at delivery, birth weight, and the presence and type of major or minor birth defects.	None
Zhang, 2016	retrospective cohort	Medical records	Medical records. Antenatal care was also conducted monthly to record the pregnancy status and the health conditions of fetuses.	None

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