Alprazolam - Medication and Pregnancy KB

Alprazolam

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Källén, 2013	Swedish 1996 - 2011	Nearly all births in Sweden during the study period (1,575,847) are registered in The Swedish Medical Birth Register.	Infants whose mothers used alprazolam in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Infants in population whose mothers used at least one of a central nervous system active drugs (less than 3%) or weren't exposed in early pregnancy.	444 / 1575847	Follow-up period known thanks to author's email reply. For major malformations: upper CI value may be incorrect (1.97 [1.38;2.02]).
Kelty (Controls unexposed, disease free), 2023	Australia 2014 - 2018	All women who had given birth during the study period.	All women who had been dispensed two or more scripts of alprazolam during pregnancy, with a combined minimum of 40 tablets.	unexposed, disease free Women who had no record of alprazolam dispensing at any time.	48 / 96	Women in this group were dispensed a median of four prescriptions during pregnancy (IQR: 2–6), with a median of 200 tablets (IQR: 100–357) dispensed during pregnancy.
Kelty (Controls unexposed, sick), 2023	Australia 2014 - 2018	All women who had given birth during the study period.	All women who had been dispensed two or more scripts of alprazolam during pregnancy, with a combined minimum of 40 tablets.	unexposed, sick All women who had been dispensed alprazolam prior to conception or following birth (but not during pregnancy)	48 / 96	Women in this group were dispensed a median of four prescriptions during pregnancy (IQR: 2–6), with a median of 200 tablets (IQR: 100–357) dispensed during pregnancy.
Lee, 2022	South Korea 2000 - 2019	Pregnant women who participated in in the Mother-Safe Program, a teratogen information service that provides evidence-based information on the safety and risk of exposure during pregnancy.	Pregnant women exposed to alprazolam during pregnancy.	unexposed (general population or NOS) Pregnant women exposed to non-teratogenic drugs including acetaminophen and chlorpheniramine during pregnancy.	96 / 629	The main reasons for taking alprazolam were irritable: bowel syndrome (IBS) (20.8%), depression (16.7%), and common cold (12.5%). Cumulative doses during pregnancy ranged from 1.00 mg/kg to 61.00 mg/kg (median 16.00 mg/kg).
Meng a (Controls unexposed, sibling), 2023	Taiwan 2004 - 2018	All singleton pregnancies of females aged 15–50 years who gave birth during the study period.	Sibling with at least one Alprazolam prescription received by the mother during early pregnancy (the first 20 weeks of pregnancy).	sibling Discordant matched sibling without benzodiazepine or Z-hypnotic prescriptions from 30 days before the date of the estimated last menstrual period to the end of the 20th week of pregnancy.	-9 / -9	Number of exposures not provided (authors provided number of Exposure discordant pairs and number of Case discordant pairs).
Meng a (Controls unexposed, sick), 2023	Taiwan 2004 - 2018	All singleton pregnancies of females aged 15–50 years who gave birth during the study period.	At least one Alprazolam prescription received by a mother during early pregnancy (the first 20 weeks of pregnancy).	unexposed, sick Pregnant women with no benzodiazepine or Z-hypnotic prescriptions from 30 days before the date of the estimated last menstrual period to the end of the 20th week of pregnancy.	14299 / 2771325	Use of results obtained with PS-FSW because more exposures, with a sick control group and sensitivity analyses (sibling control study, and paternal negative control design) that obtained similar results.
Meng b, 2023	Taiwan 2004 - 2018	Women with pregnancies from both the two national health databases.	Women receiving at least 1 prescription of Alprazolam during the risk period only (1-28 days before miscarriage).	unexposed, sick Women receiving at least 1 prescription of Alprazolam during the reference period only (181-208 days before the last menstrual period).	136134 / 134864	Use of Case-Time-Control (CTC) Design OR => nb of exposures/cases/controls not applicable; and the main Reference period, i.e 181 to 208 days before the last menstrual period.
Noh, 2022	South Korea 2011 - 2018	All pregnancies in women aged 20 to 45 years at delivery resulting in live births from 1 January 2011 to 31 December 2018, in South Korea.	Pregnant women who filled at least Alprazolam prescription during the first trimester (first 90 days of pregnancy).	unexposed, sick Pregnant women who were not prescribed any benzodiazepine from 3 months before the last menstrual period to the end of the first trimester (with similar psychiatric conditions after propensity score).	1473 / 3053381	Propensity scored adjusted for indications and led to an unexposed cohort with similar psychiatric conditions => considered as unexposed, sick control groups.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Cifuentes, 2025	Europe (13 countries) 1995 - 2019	Registrants (liveborn, stillborn, or induced terminations) with congenital ocular anomalies (COA).	Registrants with major congenital anomalies (excluding genetic syndromes) other than congenital ocular anomalies (COA) and nervous system anomalies (except spina bifida) as central nervous system development is closely linked to eye development.	4185 / 232718	Use of nongenetic controls (cases of CA other than COA excluding genetic syndromes),
Eros, 2002	Hungary 1980 - 1996	Newborn infants with isolated congenital abnormality (CA) and multiple CA. Exclusions of some mild congenital abnormalities and minor congenital abnormality (methods in Czeizel 1999).	Two or three newborn infants without congenital anomalies matched to every case according to sex, birth week in the year when the case was born, and district of parents’ residence from the National Birth Registry of the Central Statistical Office.	22865 / 38151
Laspro, 2024	USA 2013 - 2023	Newborns with oral clefts (ICD 10 codes Q35 or Q36 or Q37).	Newborns without oral clefts.	12098 / -9	P-values were calculated, while to account for multiple testing (693 hypotheses) Benjamini-Hochberg (BH) corrections were performed with a false discovery rate (Q) of 0.05 => use of Table 4. Bejamini Hochberg Correction when available.
Sheehy, 2019	Canada 1998 - 2015	Pregnancies ending with spontaneous abortion (pregnancy loss between between the beginning of the sixth week of gestation and the 19th completed week of gestation, excluding planned or induced abortions).	Pregnancies ending with live births (5 for each case) randomly selected at the index date and matched with the case pregnancy by gestational age and calendar year.	27149 / 134305
Tinker, 2019	USA 1997 - 2011	Live bom, stillborn, or induced terminations with at least one of the 30 different birth defects (excluding chromosomal or monogenic disorders) diagnosed prenatally, at birth, or during the first year of life.	Liveborn infants without major birth defects identified on the same catchment area and month of birth as the cases.	-9 / 11614	Total number of cases not provided by authors (number of cases provided for each kind of malformations or group of malformations).

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