Beta-blockers (All routes except ocular) (versus unexposed)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Al Khalaf - Beta-blockers (Controls unexposed, disease free), 2022	retrospective cohort (claims database)	Data on antihypertensive medication were identified from the Clinical Practice Research Datalink (CPRD) provides information about prescription details.	Outcomes were measured based on read or ICD-10 codes of diagnoses available in the Hospital Episodes Statistics (HES) data base.	No match/adjustment for this group of comparison.
Al Khalaf - Beta-blockers (Controls unexposed, sick), 2022	retrospective cohort (claims database)	Data on antihypertensive medication were identified from the Clinical Practice Research Datalink (CPRD) provides information about prescription details.	Outcomes were measured based on read or ICD-10 codes of diagnoses available in the Hospital Episodes Statistics (HES) data base.	No match/adjustment for this group of comparison.
Albertini - Beta-blockers, 2023	retrospective cohort	Maternal clinical history including medications was collected (no other details).	Data regarding pregnancy and labor outcomes were collected, including fetal losses, birth weight, gestational age, type of delivery, and labor complications (no other details).	No adjustment. Twin pregnancies were excluded.
Baard - Beta-blockers, 2020	prospective cohort	Data were manually extracted from both cardiology and obstetric clinical records, after screening for eligibility, and captured in a modified database. Data on type of beta-blockers (BB) used, treatment dosage, treatment duration in weeks and trimester of BB initiation were recorded.	Data were manually extracted from both cardiology and obstetric clinical records, after screening for eligibility, and captured in a modified database. Data parameters recorded included gestational age, gender, mode of delivery, birth weight and Apgar scores for all patients.	No adjustment. No significant differences were noted between the groups for clinical and echocardiographic parameters, body mass index, parity, rate of chronic hypertension, HIV, family history of cardiovascular disease.
Bateman - Beta-blockers, 2016	retrospective cohort (claims database)	Claims database of dispensed prescriptions for outpatient medications.	The outcomes were obtained in the infant records (at least 1 diagnostic code from the ICD-9 indicating the presence of neonatal hypoglycemia or bradycardia). Recordings of the diagnostic codes were identified for 1 month after delivery to allow for potential lags in the posting of claims.	Propensity score for maternal age, maternal ethnicity, maternal heart disease, gestational and preexisting hypertension, gestational and preexisting diabetes, preterm, multiple gestation, alcohol abuse, illicit drug use, tobacco use, chronic renal disease, essential tremor, overall burden of comorbidity, maternal exposure to insulin or oral hypogylcemics in the final month of pregnancy...
Bateman_Nordic - Beta-blockers, 2018	population based cohort retrospective	Exposure was determined through the nationwide prescription drug registries in the Nordic cohort.	In the Nordic cohort, data on congenital malformations was retrieved from the medical birth, patient, and cause-of-death registries (according to ICD-9 or 10 codes).	Controlled for maternal age at delivery, calendar year of birth, parity, diabetes, diabetes treatments in early pregnancy and country of origin using propensity scores. Singletons only. Both cohorts excluded pregnancies in which a woman filled a prescription for a known teratogenic medication.
Bateman_USMAX - Beta-blockers, 2018	retrospective cohort (claims database)	Exposure was determined by review of pharmacy dispensing records in the US MAX cohort.	In USA cohort, data were based on inpatient and outpatient ICD-9 diagnoses and procedure codes in the maternal or infant record.	Controlled for maternal age at delivery, calendar year of birth, parity, diabetes, diabetes treatments in early pregnancy, maternal race/ethnicity, renal disease, overweight or obesity, smoking, alcohol abuse, illicit drug use, multiple gestations, and exposure to potential teratogens, using propensity scores. Singletons only.
Bayliss - Atenolol, 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).	The variables entered into the Multiple Logistic Regression model included drug treatment, ethnic origin, maternal height and weight, diastolic and systolic pressures, smoking, fetal sex, proteinuria and gestational age at delivery.
Bergman - Beta-blockers, 2018	case control	Medication exposure was obtained from the mother’s medical files (mostly these are only files relating to the pregnancy) and from the child’s, except for the Tuscany registry, which only collects data on medication use via a questionnaire sent to the mother after birth of the malformed child.	EUROCAT registries collect data on all pregnancy outcomes: live births, foetal deaths >= 20 weeks of gestational age (including stillbirths) and terminations of pregnancy for foetal anomalies (TOPFAs) with a major congenital anomaly.	Adjusted for registry, maternal age, use of other anti-hypertensive medications, birth year and pregnancy outcome (live births, stillbirths or terminations of pregnancy). Exclusion of registrations with maternal diabetes and/or insulin use during pregnancy, maternal epilepsy and/or anti-epileptic medication use during pregnancy and registrations with the use of highly teratogenic medication.
Caton - Beta-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. Exclusion of pregnancies with multiple births or preexisting diabetes mellitus. Smoking and use of caffeine, alcohol, cocaine, or crack; vasoactive medications; anticonvulsants; oral contraceptives; and folic acid/multivitamins during the periconception period were also examined.
Cedergren - Beta-blockers, 2002	nested case control	For the register study, the exposure information was extracted from the Medical Birth Register, recorded at the mother’s first visit to the antenatal care center (usually week 10–12 of pregnancy), prior to knowledge of the outcome.	Outcome data were identified from various medical health registers: the Medical Birth Register and the Child Cardiology Register.	Controls matched for the region, the year of birth and maternal age.
Chan - Labetalol, 2010	prospective cohort	Prospectively collected database with participants contacting the Motherisk Program for counseling in case of use of medication during pregnancy.	Medical and psychological examinations (notably neurocognitive assessment) were performed on children by psychometrist and physician, both blinded to the participant’s group membership.	Controls were matched for age at delivery, children's gender and age at testing. Exclusion of mothers exposed to a known teratogen, on account of substance abuse and co-morbid illnesses which may have affected the child’s neurodevelopment (e.g., renal failure, diabetes, severe anemia, and psychiatric illness). No differences of alcohol use and maternal IQ.
Cruickshank - Labetalol, 1990	randomized controlled trial	The study women were randomly allocated using numbered sealed envelopes to receive either oral labetalol or no specific antihypertensive therapy (according Cruickshank et al. 1992).	Antenatally, pregnant women were all seen at least weekly as out-patients (according Cruickshank et al. 1992).	No adjustment. Randomisation. Singleton pregnancies only. Additional exclusion criteria were asthma, diabetes mellitus, psychosis, several psychoneuroses or any cardiac abnormality precluding the use of beta-blockers.
Cruickshank - Labetalol, 1991	randomized controlled trial	Pregnant women were randomly allocated using numbered sealed envelopes to receive either oral labetalol or no antihypertensive drug therapy.	Obstetric management decisions for both groups were based on current practice and independent of group allocation. Delivery was expedited when the clinican felt the risk to the fetus or mother was greater if the pregnancy continued.	No adjustment. Randomisation. Singleton pregnancies only. Additional exclusion criteria were asthma, diabetes mellitus, psychosis, several psychoneuroses or any cardiac abnormality precluding the use of beta-blockers.
Darcie - Atenolol, 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.
Delteil - Beta-blockers, 2024	retrospective cohort (claims database)	Women's drug exposure during pregnancy was estimated on the basis of dispensed prescription drugs recorded by the French Assurance Maladie.	Pregnancy outcomes were obtained from compulsory health certificates at 8 days, 9 months and 2 years for children recorded by the Protection Maternelle et Infantile (PMI) for births, and from data from the Primary Health Insurance Fund and the Toulouse University Hospital.	All analyses adjusted for maternal age and the number of other medications during pregnancy. SGA: also adjusted for diabetes and child sex. Preterm: also adjusted for the presence of a long-term medical condition (ALD). Malfo and intrauterine deaths (IUD): also adjusted for folic acid intake, diabetes, exposure to at least one teratogenic drug (and also ALD for IUD).
Duan - Beta-blockers, 2017	retrospective cohort (claims database)	Pregnant women exposed to β-blockers during pregnancy were identified using pharmacy dispensing records.	Fetal congenital anomalies were identified by searching electronic medical records using ICD-9-CM codes. Fetal birth weights were obtained from California birth certificates.	Multivariate adjustment for maternal age, gestational age at delivery, white race, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), maternal comorbidities (hypertension, hyperlipidemia, diabetes, congenital heart disease, heart failure, coronary artery disease, stroke, arrhythmia, chronic kidney disease). Singleton pregnancies only.
Duan - Beta-blockers, 2018	retrospective cohort (claims database)	Pregnant women exposed to beta‐blockers during their pregnancy were identified using pharmacy dispensing records.	This study utilized computerized electronic health system databases which includes inpatient and outpatient diagnoses, patient vital statistics,... Fetal birth weights were obtained from California birth certificates.	For SGA: multivariable logistic regression models were constructed to adjust for maternal age, gestational age, maternal race and ethnicity, body mass index, and maternal comorbidities (including hypertension, hyperlipidemia, diabetes, heart failure, stroke, arrhythmia, and renal insufficiency). Only singleton pregnancies.
Ersboll - Beta-blockers (Controls unexposed, disease free), 2014	retrospective cohort	Electronic summary charts for all women attending the Centre for Pregnant Women with Heart Disease (CPWHD) during the study period were screened. Data on any medical treatment taken at the time of conception and/or during pregnancy were collected from obstetrical and cardiological charts.	Obstetric complications, mode of delivery and pregnancy outcomes (gestational age at birth, birthweight, Apgar scores, malformations, blood glucose levels) were collected from obstetrical, cardiological, and neonatal hospital charts, and then manually entered into a custom-made database.	The groups were matched on the following seven birthweight-determining factors: maternal BMI; maternal smoking habits; parity; gestational age at delivery; fetal gender; gestational diabetes mellitus (GDM); and hypertensive disorders of pregnancy, including pre-eclampsia and the haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Only singleton pregnancies.
Ersboll - Beta-blockers (Controls unexposed, sick), 2014	retrospective cohort	Electronic summary charts for all women attending the Centre for Pregnant Women with Heart Disease (CPWHD) during the study period were screened. Data on any medical treatment taken at the time of conception and/or during pregnancy were collected from obstetrical and cardiological charts.	Obstetric complications, mode of delivery and pregnancy outcomes (gestational age at birth, birthweight, Apgar scores, malformations, blood glucose levels) were collected from obstetrical, cardiological, and neonatal hospital charts, and then manually entered into a custom-made database.	Small for gestational age adjusted for Body mass index. Only singleton pregnancies. The 2 groups are comparable in terms of: maternal age, smoking habits; type of heart disease according to groups in WHO, cardiac functional class; left ventricular ejection fraction assessed as either normal or low (<45%); parity. No illicit drug or alcohol abuse was registered.
Fidler - Oxprenolol, 1983	prospective cohort	The patients were allocated at random to receive either methyldopa or oxprenolol.	All out patients were seen every two weeks until 36 weeks' gestation and thereafter every week until delivery.	Matched for parity and gestational age at delivery. Exclusion of patients that were taking other hypertensive medication, had diabetes, expecting twins, had renal disease, and had congenital adrenal hyperplasia. No difference in smoking.
Fisher - Beta-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 - Beta-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 - Beta-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, BMI, parity, pregestational type 1 or type 2 diabetes, and study site.
Fisher b - Beta-blockers (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.	Adjusted for: maternal race/ethnicity; maternal age at delivery; maternal prepregnancy body mass index (BMI); folic acid-containing supplement use during the first trimester; maternal cigarette smoking after the first trimester; and study site. Singletons only. Exclusion of mothers who reported preexisting diabetes.
Fisher b - Beta-blockers (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 - Beta-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 - Beta-blockers (Controls unexposed, disease free), 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 - Beta-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.
Fitton - Beta-blockers (Controls unexposed, sick), 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.	No adjustment for this group of comparison. Only singleton live birth.
Gandjbakhch - Beta-blockers, 2018	retrospective cohort	Medications characteristics were obtained from medical records.	Data on pregnancy and events in children were collected retrospectively by written questionnaire completed by subjects.	None.
Hoeltzenbein c - Bisoprolol, 2018	prospective cohort	At the initial contact (during pregnancy) maternal characteristics and detailed exposure assessment are asked for after informed consent. The outcome of pregnancy was not known at the time of enrollment.	About 8 weeks after the estimated date of birth, information on course and outcome of pregnancy is collected via structured telephone interview or mailed questionnaires. For neonates, information on the third German pediatric examination at age of 4– 5 weeks is included.	Adjusted fo maternal age, body mass index, pregestational diabetes, alcohol consumption, smoking status, and numbers of previous deliveries, previous spontaneous abortions and previous children with birth defects. Pregnancies exposed to known teratogens such as vitamin-K antagonists, valproate, methotrexate or mycophenolate were excluded from the exposed and the control groups.
Ishibashi - Beta-blockers, 2017	retrospective cohort	All data were collected with checking their maternity record book.	All data were collected with checking their maternity record book. The infants’ data (premature birth and low birth weight) was collected from the patients’ maternity records.	None.
Kayser - Metoprolol/bisoprolol, 2020	prospective cohort	Using a structured questionnaire at the first contact, all relevant data with respect to medication (including duration, time, dosage) are documented. In the majority of cases, neither pregnancy outcome nor prenatal abnormalities are known when the institute is contacted.	Follow-up data are obtained with a second questionnaire administered to the mother. If necessary, hospital discharge letters and additional medical reports are requested. The diagnosis of bradycardia and postnatal respiratory disorder was retrieved from medical reports.	The propensity score was estimated using boosted regression trees based on maternal age, body mass index, alcohol consumption, smoking habits and number of previous deliveries as covariates . Exclusion of pregnancies with maternal concomitant medications considered as potent teratogens or fetotoxins (angiotensin system, ...), women with acute malignancies, preeclamp- sia or HELLP-syndrome.
Kubota - Beta-blockers, 2023	retrospective cohort	This was a retrospective analysis of data collected for routine clinical care. The patients were identified based on their prescription histories, and their hospital records were examined.	The patients were identified based on their prescription histories, and their hospital records were examined.	None.
Kumar - Beta-blockers, 2020	retrospective cohort	Data were collected retrospectively from the electronic medical record notably for medications including beta blocker use during current pregnancy.	Data were collected retrospectively from the electronic medical record notably for the point of care (POC) glucose level and collection time. POC levels were measured according to the standardized protocol for postnatal glucose monitoring at the institution.	Variables included in the multivariate logistic regression: glycated hemoglobin (HbA1c) level, maternal race, mode of delivery, use of general anesthesia at delivery, neonatal sex, type of feeding (breast milk vs formula), time of feeding, and timing of blood glucose check. No difference of small for gestational age.
Lennestal - Beta-blockers, 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'.
Lieberman - Propranolol, 1978	retrospective cohort	Not specified.	Not specified.	None.
Lydakis - Atenolol, 1999	retrospective cohort	A retrospective cohort study from a computerized database of a clinic => medical records.	A retrospective cohort study from a computerized database of a clinic => medical records.	No adjustment. Exclusion of pregnancies in women with diabetes, renal diseases, secondary forms of hypertension. There were no statistically significant differences between the groups in terms of age, initial Body Mass Index, smoking habits, proportion of multigravidae, and history of previous miscarriages.
Mazkereth - Beta-blockers, 2019	retrospective cohort	Medical files of infants.	Medical files of infants.	Matched controls (not otherwise specified). Exclusion of infants born to mothers who used psychiatric medications (such as opiates, benzodiazepines, tricyclic antidepressants), alcohol or drugs during pregnancy, because it may affect postnatal clinical signs.
Medveczky - Pindolol, 2004	case control	Exposure data collected from 3 sources: a post-paid structured questionnaire sent to the parents requesting drugs taken during pregnancy, according to gestational months; maternal prenatal care logbook (in which obstetricians must record all prescribed drugs); nurses visited non-responding families.	The Hungarian Congenital Abnormality Registry (HCAR), in which notification by physicians of cases with Congenital anomalies is mandatory (including infant deaths and usual stillborn fetuses). Controls were selected from the National Birth Registry of the Central Statistical Office.	Controls matched according to sex, birth week, and district of parents' residence. Multivariable unconditional logistic regression model for maternal age, birth order, and employment status.
Nakhai-Pour - Beta-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.
Orbach - Atenolol, 2013	retrospective cohort (claims database)	The medication data of Clalit members are stored in the Clalit data warehouse. This database contains information about dispensing date, the ATC code of the drug (including the commercial and generic names), dose schedule of drugs administration, and dose dispensed in defined daily dose.	Two computerized databases: the database of the Obstetrics and Gynecology Department which includes information on maternal medical conditions during pregnancy and delivery; and the Demog-ICD9 which includes medical diagnoses during hospitalization, drawn directly from the medical records.	The models were controlled for maternal age, ethnicity, smoking, diabetes mellitus, twin pregnancies, lack of prenatal care and parity.
Petersen - Beta-blockers, 2012	population based cohort retrospective	Information on redeemed prescriptions was retrieved from the National Prescription Register, which holds information on date of redemption, quantity, strength and form. Exposure to b-blockers by identifying redeemed prescriptions with ATC code C07.	The Danish National Hospital Register contains information on diagnoses of somatic admissions and outpatients at all Danish hospitals, inaccordance with the ICD-10 system.	Adjusted for maternal age, year of conception, annual household income, parity and educational level (model 1). Model 2: additional confounding variables: smoking status, comedication (yes/no) with statins, antiobesity drugs, insulin and insulin analogues, and diagnoses of pre-eclampsia/eclampsia. Post hoc propensity score-matched regression analysis was carried out.
Puho - Metoprolol, 2007	case control	Mothers were asked to send their prenatal maternity logbook and other medical records and they were mailed a questionnaire. Regional nurses were asked to visit and question the non-respondent.	Notification by physicians to the Hungarian Congenital Abnormality Registry. Pathologists sent a copy of each autopsy report to the registry for stillborn fetuses or infant deaths and defect diagnosed in prenatal diagnostic centers with or without termination of pregnancy were included.	Adjusted for maternal age and employment status, parity and acute maternal diseases in the 2nd and/or 3rd months of pregnancy. Controls were matched according to sex, week of birth in the year when the case was born, and district of parent’s residence.
Puho - Oxprenolol, 2007	case control	Mothers were asked to send their prenatal maternity logbook and other medical records and they were mailed a questionnaire. Regional nurses were asked to visit and question the non-respondent.	Notification by physicians to the Hungarian Congenital Abnormality Registry. Pathologists sent a copy of each autopsy report to the registry for stillborn fetuses or infant deaths and defect diagnosed in prenatal diagnostic centers with or without termination of pregnancy were included.	Adjusted for maternal age and employment status, parity and acute maternal diseases in the 2nd and/or 3rd months of pregnancy. Controls were matched according to sex, week of birth in the year when the case was born, and district of parent’s residence.
Queisser-Luft - Beta-blockers, 1996	nested case control	Two sources of information: the health report of the gynecologist, and anamnestic data recorded by the delivery-hospital staff approximately 6 weeks prior to birth.	All examinations were performed in the first week of life of livebirths by four pediatricians trained in clinical genetics. For stillbirths and abortions, pathological findings were used.	No adjustment.
Ray - Beta-blockers, 2001	prospective cohort	Mother data were abstracted from their hospital charts by two authors three months after the patient's date of confinement.	Mother and infant data were abstracted from their hospital charts by two authors three months after the patient's date of confinement (3 month delay to allow for the recording of complete information on early infant outcomes). Data were recorded using a standard data collection form.	Singleton only. Adjusted for maternal age, parity, pre-pregnancy weight, history of delivery before 34 weeks, history of hypertension in a previous pregnancy, cigarette smoking, pre-pregnancy diabetes mellitus or renal dysfunction, use of prednisone, betamethasone for fetal lung maturity (not included in the analyses of SGA and preterm delivery), and gestational age at first high blood pressure.
Rosenfeld - Pindolol, 1986	randomized controlled trial	Patients were randomly allocated to one of two groups, who were treated with either hydralazine alone, or with hydralazine combined with pindolol.	Placental and fetal growth rate were monitored by serial plasma estriol estimations and ultrasonography of the fetal biparietal diameter. Cardiotocography was performed at weekly intervals from the 34th wk of gestation or in case of complications. The status of the neonate at birth was assessed.	No adjustment. Randomisation. Patients were excluded from the study if they suffered from obstructive lung disease, insulin-dependent diabetes or any other condition constituting a contraindication for therapy with hydralazine or pindolol.
Sibai - Labetalol, 1990	randomized controlled trial	Eligible patients were randomly allocated to one of the 3 groups based on a computer-generated list of random numbers. The random allocation allowed patients who were already taking antihypertensive medication to be changed to a new type of management.	Maternal and perinatal outcomes reported.	No adjustment. Randomisation. Patients with associated medical complications (other than chronic hypertension) were excluded.
Su - Beta-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 - Beta-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.
Syvanen - Beta-blockers, 2021	nested case control	Information on maternal prescription medicine use was obtained from the Register on Reimbursed Drug Purchases and the Register on Medical Special Reimbursements (Social Insurance Institution of Finland).	Cases and controls were identified from the National Register of Congenital Malformations, the Medical Birth Register and the Register on Induced Abortions.	Matched for residency and time of conception. Multivariable analysis adjusted for maternal age, primiparity, and pregestational diabetes. Other potential maternal risk factors analyzed: body mass index, smoking, long-term diseases (asthma, psychotic mental conditions, depression, epilepsy, and inflammatory bowel diseases), history of miscarriages, utilization of assisted reproductive technology.
Tanaka - Beta-blockers, 2016	retrospective cohort	Patient data were collected from their medical records and included medication(s) used (β-blockers and other ones).	Patient data were collected from their medical records.	Fetal growth restriction adjusted for maternal age, parity, maternal body mass index, primiparity, smoking, drinking, hypertension, thyroid disease, gestational diabetes mellitus, and NYHA class. Singleton only. Smoking and alcohol consumption during pregnancy not observed in any of the patients. No significant differences in gestational DM and pregnancy-induced hypertension between the 3 groups.
Thewissen - Labetalol (Controls unexposed, disease free), 2017	prospective cohort	Obstetrical data were collected from the hospital record. Prenatal maternal exposure and maximum dose and route of labetalol were noted.	Neonatal data were collected prospectively (no more details).	Matched for sex, gestational age and birthweight. Exclusion criteria were neonates with known or strongly suspected congenital abnormalities.
Thewissen - Labetalol (Controls unexposed, sick), 2017	prospective cohort	Obstetrical data were collected from the hospital record. Prenatal maternal exposure and maximum dose and route of labetalol were noted.	Neonatal data were collected prospectively (no more details).	Matched for sex, gestational age and birthweight. Exclusion criteria were neonates with known or strongly suspected congenital abnormalities.
Vaclavik - Beta-blockers, 2024	population based cohort retrospective	The National Registry of Reimbursable Health Services (NRHZS).	Nationwide data on all births and abortions in the Czech Republic were obtained from the National Registry of Reproductive Health (NRRZ).	None.
Van Zutphen - Beta-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 - Beta-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.
Xiang - Labetalol, 2020	randomized controlled trial	A simple random table was used for randomization after selection. In a 1:1:1 ratio patient was divided randomly into three groups.	Regular prenatal and postnatal visits continue, and the obstetric outcomes of the participants are registered.	No adjustment. Randomisation. Women with multiple embryos, prior proteinuria, and other conditions such as diabetes and asthma) as well as fetal defects during pregnancy were removed from the research. In terms of age, delivery numbers and body mass index, and systolic and diastolic blood pressure at the registration date, there were no major variations in demographic variables.
Yassen - Acebutolol, 1992	prospective cohort	Not specified.	Fetal heart recorded with a cardiotocograph Hewlett-Pachard. Neonates were monitored for weight, feeding, continous cardio-repiratory monitoring, blood pressure (every 6h) and biochemical monitoring (glycemia, creatine, ...) and renal function (diuresis, glomerular and tubular functions, ...).	Control group matched on gestational age, neonatal weight, length and head circumference. Exclusion of neonates whose mother had renal disease, neonates with congenital malformations, ventilated, or with other treatments than could have an impact on renal function.

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