Benzodiazepines (Psy and mixed indications) updated on 02-10-2025

Small for gestational age (weight)

id	Study   Auto Li, 2026Christensen - Clonazepam (Indications other than epilepsy), 2024Chan - BZDs, 2023Kelty - Alprazolam (Controls unexposed, disease free), 2023Kelty - Alprazolam (Controls unexposed, sick), 2023Meng - BZDs (Controls unexposed, sibling), 2023Meng - BZDs (Controls unexposed, sick), 2023Coste - Clonazepam (Mixed indications), 2020Källén - BZDs, 2013Calderon-Margalit - BZDs, 2009	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S19615 R83654	Li, 2026	Small for gestational age	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Not specified	1.06 [1.00;1.09]	2,753/54,892   30,359/384,391	33,112	54,892		ref
S16811 R70536	Christensen - Clonazepam (Indications other than epilepsy), 2024	Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations))	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: No (among antiseizure medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...)	1.22 [1.02;1.45]	164/1,019   443,851/4,445,621	444,015	1,019		ref
S15397 R63467	Chan - BZDs, 2023	Small for gestational age (birth weight <2 standard deviations [SD] below the mean for gestational age)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	0.61 [0.34;1.07]	12/1,060   9,028/531,164	9,040	1,060		ref
S15488 R63666	Kelty - Alprazolam (Controls unexposed, disease free), 2023	Low birth weight for gestational age	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free excluded	Adjustment: No BZD Coexposure: Not specified	3.27 [1.22;8.79] C excluded (control group)	11/48   8/96	19	48		ref
S15487 R63662	Kelty - Alprazolam (Controls unexposed, sick), 2023	Low birth weight for gestational age	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No BZD Coexposure: Not specified	4.46 [1.54;12.95] C	11/48   6/96	17	48		ref
S17848 R75325	Meng - BZDs (Controls unexposed, sibling), 2023	Small for gestational age (birthweight below the 10th percentile for gestational age by sex)	early pregnancy	population based cohort retrospective	sibling excluded	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	1.15 [1.07;1.23] excluded (control group)	-/-   -/-	-	-		ref
S15409 R63481	Meng - BZDs (Controls unexposed, sick), 2023	Small for gestational age (birthweight below the 10th percentile for gestational age by sex)	early pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	1.15 [1.12;1.18]	6,859/61,220   271,318/2,747,697	278,177	61,220		ref
S15584 R64108	Coste - Clonazepam (Mixed indications), 2020	Small for gestational age (weight)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No BZD Coexposure: No (among antiseizure medications)	1.35 [1.14;1.59] C	159/1,246   167,376/1,710,441	167,535	1,246		ref
S15587 R64165	Källén - BZDs, 2013	Small for gestational age (NOS)	2nd and/or 3rd trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Not specified	1.23 [0.96;1.58]	58/-   -/-	-	-		ref
S15320 R63034	Calderon-Margalit - BZDs, 2009	Small for Gestational Age infant (birth weight 2 standard deviations below the mean for the newborn’s gestational age at birth)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	0.83 [0.24;2.88]	3/85   70/2,493	73	85		ref
					Total	8 studies	1.16 [1.06;1.26]		931,969	119,570
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 15488, 17848

Umbrella review (other published meta-analyses)