Diazepam - Medication and Pregnancy KB

Diazepam

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Ban (Other indications) (Controls unexposed, disease free), 2014	United Kingdom 1990 - 2010	All singleton live births for women aged 15–45 years included in the Health Improvement Network (THIN) (covering 5% of the total UK population).	Children born to women with prescription of diazepam (without concurrent prescriptions of antidepressants) in women’s primary care electronic health records from four weeks before the estimated onset of the last menstrual period up to 12 weeks.	unexposed, disease free Children born to women without depression or anxiety.	1159 / 351785	This study assessed 2 different benzodiazepines. In order to avoid redundancy of controls, only 1 was reported in the meta-analysis of class, i.e the substance with the most exposures (i.e Diazepam).
Ban (Other indications) (Controls unexposed, sick), 2014	United Kingdom 1990 - 2010	All singleton live births for women aged 15–45 years included in the Health Improvement Network (THIN) (covering 5% of the total UK population).	Children born to women with prescription of diazepam (without concurrent prescriptions of antidepressants) in women’s primary care electronic health records from four weeks before the estimated onset of the last menstrual period up to 12 weeks.	unexposed, sick Children born to women with depression or anxiety but with no first trimester psychotropic medication.	1159 / 19193	Unexposed sick: Depression or anxiety (including generalised anxiety disorder, panic attacks, insomnia and other anxiety related disorder) in the year before pregnancy or during pregnancy. Only Diazepam was reported in the class MA (control redundancy).
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 Diazepam 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.	865 / 1575847	Follow-up period known thanks to author's email reply.
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 Diazepam 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 Diazepam 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.	13726 / 2771077	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 Diazepam during the risk period only (1-28 days before miscarriage).	unexposed, sick Women receiving at least 1 prescription of Diazepam 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 Diazepam 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).	17923 / 3053381	Propensity scored adjusted for indications and led to an unexposed cohort with similar psychiatric conditions => considered as unexposed, sick control groups.
Shiono, 1984	USA Not specified.	Not specified.	Pregnant women that had used diazepam during the first trimester of pregnancy.	unexposed (general population or NOS) Pregnant women that had not used diazepam during the first trimester of pregnancy.	854 / 32395

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Aarskog, 1975	Norway 1967 - 1975	Infants with oral clefts only (without additional major birth defects).	Infants without malformations.	-9 / 362
Bracken, 1981	USA 1974 - 1976	All newborns and stillborns with major congenital malformations, delivered at 5 major Connecticut hospitals and at 2 pediatric clinics or delivered elsewhere and referred to the 5 hospitals before 1 year of age.	Sampling of all apparently healthy live births in the 5 major Connecticut hospitals, randomly selected (subsequent ones from the delivery room log book).	1370 / 2968	This study assessed 2 different benzodiazepines. In order to avoid redundancy of controls, only 1 was reported in the meta-analysis of class, i.e the substance with the most exposed cases (i.e Diazepam).
Czeizel, 1987	Hungary 1970 - 1976	Infants born with facial clefting born during the study period.	Infants born witout facial clefting born during the study period.	1201 / 1201	Use of Retrospective case control study. This study assessed 3 different benzodiazepines. In order to avoid redundancy of controls, only 1 was reported in the meta-analysis of class, i.e the substance with the most exposed cases (i.e Diazepam).
Czeizel, 2003	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 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	Overlapping: same data used by Kjaer 2007. The main analysis (both maternal self-reported and medically recorded) was reported here (even if the only medically recorded (logbooks and discharge summaries) was also evaluated separately).
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.
Rosenberg, 1983	USA 1976 - 1982	Children with oral clefts (cleft lip with or without cleft palate; cleft palate alone).	Children with all other malformations.	611 / 2498	Cases of cleft lip with or without cleft palate: n= 445; and cases of cleft palate alone: n=166.
Rothman, 1979	USA 1973 - 1975	All infants with congenital heart disease born to Massachusetts women.	Births selected randomly from the roster of all Massachusetts births.	390 / 1254	This study assessed 2 different benzodiazepines. In order to avoid redundancy of controls, only 1 was reported in the meta-analysis of class, i.e the substance with the most exposed cases (i.e Diazepam). Use of 90% confidence interval provided.
Safra, 1975	USA Not specified.	All interviewed mothers who had infants with the birth-defect rubric being examined (in particular cleft lip with or without cleft palate).	All interviewed mothers except those who had infants with the birth-defect rubric being examined.	49 / 229
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
Tikkanen, 1991	Finland 1982 - 1983	All infants born in Finland with a ventricular septal defect (VSD),diagnosed between the 20th week of gestation and one year of age, and verified by paediatric cardiologists.	Non-malformed infants randomly selected from all deliveries.	150 / 756
Tikkanen, 1992	Finland 1982 - 1983	Infants (live and stillbirths) with cardiovascular malformations, diagnosed by echocardiography, cardiac catheterization, surgery, or autopsy.	Non-malformed infants randomly selected from all deliveries.	406 / 756
Tikkanen, 1992	Finland 1982 - 1983	All infants born in Finland with a conus arteriosus syndrome (CAS), diagnosed between the 20th week of gestation and one year of age, and verified by paediatric cardiologists.	Non-malformed infants randomly selected from all deliveries.	90 / 756
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. For analyses of hypospadias, only male control infants were included => OR not provided and insufficient data to be calculated.

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