Alprazolam

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Cifuentes, 2025	case control	Information on maternal medication exposure was primarily obtained from maternity records. Additional data sources for some registries included: infant medical records, general practitioner records, pregnancy passports, and maternal interviews conducted before or after birth. EFEMERIS: dispensing.	Cases and controls were obtained in registries from EUROCAT, the European network for surveillance of congenital anomalies.	Exclusions of mothers who reported with the use of known major teratogens and infectious diseases during pregnancy that could had have an impact on eye development. Adjusted by 5-years periods, maternal age at delivery and EUROCAT registry.
Eros, 2002	case control	Exposure data collected from 3 sources: a post-paid structured questionnaire sent to the parents immediately after the selection of cases/controls; 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 to every case according to sex, birth week in the year when the case was born, and district of parents’ residence. No adjustment for this group of exposure.
Källén, 2013	population based cohort retrospective	At the midwife interview at the first antenatal care visit, the woman was asked if she had used any drugs since she became pregnant. Or determined by the use of the Swedish Register of Prescribed Drugs (since 2006).	The Swedish Medical Birth Registry contain information based on standardized medical records from the first and further antenatal visit, the delivery and the paediatric examination. Supplemented with data from the Register of Birth Defects and Hospital Discharge Register.	Adjustment was made for year of birth, maternal age (5-year class), parity, smoking in early pregnancy and body mass index.
Kelty (Controls unexposed, disease free), 2023	retrospective cohort	Prescription database.	For the neonate, the Midwives Notification System, Hospital Morbidity Data Collection, and the Western Australia Death Register were used to ascertain information on neonatal health outcomes. Characteristics of labor and delivery were taken from the Midwives Notification System.	Comparison groups were matched 2:1 to the alprazolam during pregnancy group on smoking status during pregnancy, maternal age and having previously been pregnant (yes/no). Singleton pregnancies only. No difference of maternal age, smoking, maternal diabetes, socio-economic indexes for area.
Kelty (Controls unexposed, sick), 2023	retrospective cohort	Prescription database.	For the neonate, the Midwives Notification System, Hospital Morbidity Data Collection, and the Western Australia Death Register were used to ascertain information on neonatal health outcomes. Characteristics of labor and delivery were taken from the Midwives Notification System.	Comparison groups were matched 2:1 to the alprazolam during pregnancy group on smoking status during pregnancy and having previously been pregnant (yes/no). Singleton pregnancies only. No difference of maternal age, smoking, maternal diabetes, socio-economic indexes for area.
Laspro, 2024	nested case control	Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy.	Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records.	None.
Lee, 2022	prospective cohort	Medications taken during pregnancy were asked at the time of counselling. In addition, the daily dose, duration of alprazolam administration, and the reason for taking it were asked in the exposed group.	Not specified.	Adjusted for age, parity, body mass index, alcohol intake, smoking, education, and occupation.
Meng a (Controls unexposed, sibling), 2023	population based cohort retrospective	The National Health Insurance (NHI) database that comprises anonymised health insurance claims for visits, procedures, and prescriptions for more than 99% of the population in Taiwan (about 23 million).	The National Birth Certificate Application (BCA) database that includes notably gestational age at birth, birth date of newborns, singleton or multiple pregnancy, birthweight, and birth outcomes.	Siblings. Singletons only. Adjusted for maternal age, sex of the infant, birth year, psychiatric medical conditions, tobacco use, alcohol use, drug abuse, and obstetric comorbidity index scores.
Meng a (Controls unexposed, sick), 2023	population based cohort retrospective	The National Health Insurance (NHI) database that comprises anonymised health insurance claims for visits, procedures, and prescriptions for more than 99% of the population in Taiwan (about 23 million).	The National Birth Certificate Application (BCA) database that includes notably gestational age at birth, birth date of newborns, singleton or multiple pregnancy, birthweight, and birth outcomes.	Singletons only. Propensity score (PS-FSW) to control for maternal age and nationality, sex of the infant and year of birth, indications for use (eg, anxiety, insomnia, depression, schizophrenia, epilepsy, and bipolar disorder), lifestyle factors (obesity, tobacco, alcohol, ...), chronic maternal comorbidities (hypertension, diabetes, ...), medication use, obstetric comorbidity, health-care use.
Meng b, 2023	other	The National Health Insurance (NHI) database that comprises anonymized prescriptions for more than 99% of the population in Taiwan.	The National Health Insurance (NHI) database that comprises anonymized health insurance claims for visits and procedures for more than 99% of the population and the Birth Certificate Application (BCA) database (all live births and stillbirths > 20 gestational weeks or birth weight > 500g).	Controls matched for the birth year and a disease risk score (based on age, psychiatric medical conditions, lifestyle factors (obesity, tobacco, alcohol, drug misuse), chronic comorbidities (diabetes, hypertension, hyperlipidemia, …), medication use, and health care use). Adjusted for the comedication use (antidepressants, opioid analgesics, anticonvulsant, Z-hypnotics, and other anxiolytics).
Noh, 2022	population based cohort retrospective	The Health Insurance Review and Assessment Service (HIRA) database that comprises notably healthcare utilization (e.g., drug prescription and medical procedure).	Major congenital malformations were identified by diagnostic records, according to the ICD-10 codes defined by the European Surveillance of Congenital Anomalies classification.	Exclusion of exposures to known teratogens during 1st trimester. Adjusted for maternal age, type of insurance, maternal psychiatric conditions (e.g., bipolar disorder, depression/mood disorder, anxiety, and sleep disorder), maternal conditions (e.g., epilepsy, headache, diabetes, hypertension), parity, plurality, concomitant medications (e.g., antidepressants, ...), and healthcare utilization.
Sheehy, 2019	nested case control	The Quebec Public Prescription Drug Insurance Plan database (drug name, start date, dose, and duration).	The data sources included the medical service database the Régie de l’assurance maladie du Québec (diagnoses, medical procedures, ...) and the MedEcho database (in-hospital diagnoses and procedures, including gestational age for planned abortions, spontaneous abortions, and deliveries).	Adjusted for (1) maternal sociodemographic variables (2) maternal chronic conditions (hypertension, diabetes, depression/anxiety, alcohol ...), (3) health care resources utilization, (4) pregnancy-associated variables, (5) concomitant exposure to antidepressants and/or antipsychotics. Matched by gestational age and calendar year. Exclusion of women with epilepsy and exposed to known teratogens.
Tinker, 2019	case control	Detailed information notably about medication use during pregnancy (including over-the-counter (OTC) and prescription medication) was collected from the mothers via computer-assisted telephone interviews conducted between 6 weeks and 24 months after the estimated date of delivery (EDD).	Cases were identified in the The National Birth Defects Prevention Study. The NBDPS clinical data for birth defect cases were abstracted from medical records and classified by clinical experts. Controls were selected from birth certificates or hospital records in the same area.	For associations with at least 5 exposed cases: adjusted for maternal age, race/ethnicity, maternal education, any maternal cigarette smoking or antidepressant medication use in the first trimester (no adjustment if < 5 cases). Exclusion of mothers who reported use of an antiepileptic other than a benzodiazepine in the first trimester.

master protocol