Antithyroid drugs

Study Type of data Exposure measurement Outcome assessment Adjustment
Andersen, 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). No adjustment for this group of exposure.
Andersen 2014 (MMI only), 2014 population based cohort retrospective Danish National Prescription Register. Thyroid hormones (ATC H03A) and ATD (ATC H03B) are sold solely as prescription drugs in Denmark. Information on gestational age, birth weight, and gender of the child were identified in the Medical Birth Registry. Diagnosis of birth defects was obtained from the Danish National Hospital Register. Adjusted model included birth year of the child, gender of the child, singleton/multiple pregnancy, maternal age, parity, cohabitation, maternal income, maternal origin and maternal residence.
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. No adjustment for this group of exposure.
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 obtained from the Swedish National Patient Register. No adjustment for the control group.
Azizi (MMI only), 2002 retrospective cohort Women with thyrotoxicosis who had regular follow-up in the endocrine office were recalled. Physical examination was performed, weight and height were recorded. The intelligence quotient (IQ) was evaluated by the same psychologist by Wechsler preschool and primary scale of Intelligence (WPPSI). Controls were sex and age matched.
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. Two controls matched according to sex, birth week, and district of parents’ residence. Among potential confounding factors, maternal age, birth order, marital and employment status as indicators of socio-economic status, other maternal diseases and related drug treatments, in addition folic acid/multivitamin supplements were evaluated for the primary analysis. (No adjustment for treatment effect)
Barbero (MMI only), 2008 case control A structured questionnaire was applied to all the mothers of eligible patients containing exposure during pregnancy, notably to acute and chronic maternal diseases, and medicines (detailed on the period/dose of MMI intake was also obtained (MMI is the only antithyroid drug available in Argentina)). Cases of choanal atresia were selected among patients of 3 hospitals in Argentina. Controls matched according to maternal age.
Besancon, 2014 prospective cohort Pregnant women were included prospectively and managed (with administration of ATD if needed) by the investigator. At delivery, neonates were examined by a pediatric endocrinologist who recorded predefined criteria, specifically for the study. Echocardiography and thyroid ultrasonography (US) were performed by the same ultrasonographer. None
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. Adjusted for maternal education, anaemia, hyperlipidaemia, pregestational diabetes, pregestational hypertension, hyperemesis gravidarum and infant’s gender and birth order.
Chen (control unexposed, sick), 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... None
Clementi, 2010 case control Not specified. The coverage, structure, methods, and sources of ascertainment, de- scribed 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. No adjustment for the group PTU or MMI.
Davis (PTU only), 1989 prospective cohort 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
Di Gianantonio (MMI only), 2001 prospective cohort Prospective data were collected at the time of the inquiry and included questions on commercial preparation used, its dosage, indication for use, and the time during the pregnancy when it was taken. All women or their doctors, or both, were contacted by the TIS staff by mail or telephone. The information obtained included outcome of pregnancy (termination, abortion, or delivery); birth weight, ... ; perinatal complications, and the presence and type of any major congenital malformation. None
Gianetti, 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
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).
Khoury (MMI only), 1989 case control Mothers of cases and controls were interviewed using a computer-assisted telephone questionnaire, notably whether or not they took medications for their illness, the names of specific medications, duration of treatment and intake of such medications during the index pregnancy. Cases came from the Metropolitan Atlanta Congenital Defects Programme (MACDP). Babies with malformations are ascertained via multiple methods by Centres for Disease Control trained staff, including review of hospital records, vital records, cytogenetic laboratories and specialised clinics. Odds ratios are controlled for race (matched controls), hospital of birth (matched controls), quarter of birth (matched controls), maternal age, education, and alcohol intake.
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. No adjustment for this group of exposure.
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 unexposed, disease free), 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. Multivariable logistic regression models examining the association of maternal thyroid status and birth outcome. Models are adjusted for age and race/ethnicity, with additional adjustment for infant prema- turity (birth at < 37 weeks gestation) in the model examining neonatal intensive care unit admission as the outcome.
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
McCarroll (Buckinghamshire control group) (MMI only), 1976 retrospective cohort Carbimazole was administered in every case during the first two trimesters of pregnancy then reduced in the last trimester. Psychological testing of the children were carried out for the following four factors: (1) physical health, (2) hospitalization, (3) behavioural health, and (4) inteligence quotient (IQ) by Wechsler scale. None
McCarroll (Northern Ireland control group) (MMI only), 1976 retrospective cohort Carbimazole was administered in every case during the first two trimesters of pregnancy then reduced in the last trimester. Psychological testing of the children were carried out for the following four factors: (1) physical health, (2) hospitalization, (3) behavioural health, and (4) inteligence quotient (IQ) by Wechsler scale. None
Mitsuda, 1992 retrospective cohort Review of records of patients treated in the hospital where antithyroid drugs were given during pregnancy to maintain the serum thyroid hormone level at the upper limit of normal. Review of records of patients managed in the hospital, where neonates were assessed for weight and neonatal thyroid function (assessed at birth and on fifth day after birth). None
Momotani, 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
Momotani, 1977 retrospective cohort Retrospective study of hospital records. Retrospective study of hospital records. None
Momotani (MMI only), 1984 retrospective cohort Treatment administered by physicians in the clinics. At their first visit after delivery, a doctor interviewed the mothers about the congenital malformations diagnosed by the obstetricians. Afterwards the doctor conducted examinations of the malformed infants. Not specified
Phoojaroenchanachai, 2001 retrospective cohort Extraction and analyse of the medical and obstetric records of pregnant women with present and past history of hyperthyroidism diagnosed and managed at Siriraj Hospital. Extraction and analyse of the medical and obstetric records of pregnant women with present and past history of hyperthyroidism diagnosed and managed at Siriraj Hospital. None
Rosenfeld (PTU only), 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
Schurmann, 2016 population based cohort retrospective The Danish National Patient Register (DNPR) contains data on all prescribed medication redeemed from Danish pharmacies. The Danish Medical Birth Registry or the National Patient Register (DNPR). Adjusted for year of Last menstrual period, maternal age, parity and education.
Seo, 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 this group of exposure.
Stice, 1984 retrospective cohort Records of patients treated by the authors. Records of patients treated by the authors. None
Wing, 1994 retrospective 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, 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, 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 this group of exposure.
Zhang (PTU only), 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

See the method used to produce these results