Lorazepam - Medication and Pregnancy KB

Lorazepam

Exposed non-exposed, cohort studies

Study	Country Study period Study design	Data source	Exposure definition	Non-exposure definition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks	Risk of bias
Calderon-Margalit 2009	USA 1996 - nr prospective cohort	The ongoing Omega Study, a prospective cohort study of pregnant mothers who attended prenatal care clinics affiliated with Swedish Medical Center (Seattle, Washington) and Tacoma General Hospital (Tacoma, Washington).	Pregnant women who used Lorazepam during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnant women who did not use psychotropic medications during pregnancy.	during pregnancy (anytime or not specified)	73 / 2493	Of the women who were taking psychotropic medications, 235 (78%) took only one medication, 51 (17%) used two medications, and 14 (5%) used three or more medications.
Calderon-Margalit 2009	USA 1996 - nr prospective cohort		Participants were interviewed during a prenatal visit prior to 20 weeks of gestation by trained research personnel using a structured questionnaire. Data on medications used during pregnancy were retrieved from both questionnaires and medical records.		during pregnancy (anytime or not specified)	73 / 2493
Meng a (Controls unexposed, sibling) 2023	Taiwan 2004 - 2018 population based cohort retrospective	A nationwide, population-based cohort study in Taiwan using three data sources: Taiwan’s National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database.	Sibling with at least one Lorazepam 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.	early 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, sibling) 2023	Taiwan 2004 - 2018 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).		early pregnancy	-9 / -9
Meng a (Controls unexposed, sick) 2023	Taiwan 2004 - 2018 population based cohort retrospective	A nationwide, population-based cohort study in Taiwan using three data sources: Taiwan’s National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database.	At least one Lorazepam 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.	early pregnancy	11182 / 2770460	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 a (Controls unexposed, sick) 2023	Taiwan 2004 - 2018 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).		early pregnancy	11182 / 2770460
Meng b 2023	Taiwan 2004 - 2018 other	The Taiwan’s National Birth Certificate Application database and the National Health Insurance database.	Women receiving at least 1 prescription of Lorazepam during the risk period only (1-28 days before miscarriage).	unexposed, sick Women receiving at least 1 prescription of Lorazepam during the reference period only (181-208 days before the last menstrual period).	during pregnancy (anytime or not specified)	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.
Meng b 2023	Taiwan 2004 - 2018 other		The National Health Insurance (NHI) database that comprises anonymized prescriptions for more than 99% of the population in Taiwan.		during pregnancy (anytime or not specified)	136134 / 134864
Noh 2022	South Korea 2011 - 2018 population based cohort retrospective	A nationwide retrospective cohort study using healthcare data retrieved from the Health Insurance Review and Assessment Service (HIRA) database.	Pregnant women who filled at least Lorazepam 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).	1st trimester	2468 / 3053381	Propensity scored adjusted for indications and led to an unexposed cohort with similar psychiatric conditions => considered as unexposed, sick control groups.
Noh 2022			The Health Insurance Review and Assessment Service (HIRA) database that comprises notably healthcare utilization (e.g., drug prescription and medical procedure).		1st trimester	2468 / 3053381

Case-control studies

Study	Country Study period Study design	Data source	Case	Control	Exposition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks	Risk of bias
Bonnot 2003	France 1976 - 1997 case control	European Institut of Genomutations (IEG), Lyon, France.	Infants with the studied congenital malformation.	Infants with a malformations other than this one studied.	The medical records are checked to obtain data on treatment intake and other exposures or risks.	1st trimester	-9 / -9	Total number of infants with a congenital malformation is 13703, but the number of cases changes according to the studied malformations. Raw data not sufficient to calculate OR (data for 'control' groups not available).
Bonnot 2003	France 1976 - 1997 case control	European Institut of Genomutations (IEG), Lyon, France.	After having defined a population, often on geographical criteria, these networks set up birth observatories in order to exhaustively identify neonatal malformations in their reference population.			1st trimester	-9 / -9
Laspro 2024	USA 2013 - 2023 nested case control	EPIC Cosmos, a database incorporating health information of 180 million patients, throughout the United States from approximately 180 US institutions utilizing EPIC medical records.	Newborns with oral clefts (ICD 10 codes Q35 or Q36 or Q37).	Newborns without oral clefts.	Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy.	during pregnancy (anytime or not specified)	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.
Laspro 2024	USA 2013 - 2023 nested case control		Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records.			during pregnancy (anytime or not specified)	12098 / -9
Sheehy 2019	Canada 1998 - 2015 nested case control	A nested case-control study within the Quebec Pregnancy Cohort, Montreal, Quebec, Canada.	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.	The Quebec Public Prescription Drug Insurance Plan database (drug name, start date, dose, and duration).	early pregnancy	27149 / 134305
Sheehy 2019	Canada 1998 - 2015 nested case control		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).			early pregnancy	27149 / 134305
Tinker 2019	USA 1997 - 2011 case control	The National Birth Defects Prevention Study (NBDPS), a large population-based multicenter case–control study of major birth defects.	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.	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).	1st trimester	-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.
Tinker 2019	USA 1997 - 2011 case control		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.			1st trimester	-9 / 11614

Risk of bias: : NA; : low; : moderate; : serious; : critical; : unclear;

master protocol