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

Preterm (< 37 weeks)

id	Study   Auto Li, 2026Chan - BZDs, 2023Delteil - BZDs (Controls unexposed, NOS), 2023Delteil - BZDs (Controls unexposed, sick), 2023Meng - BZDs (Controls unexposed, sibling), 2023Meng - BZDs (Controls unexposed, sick), 2023Lee - Alprazolam, 2022Zanisi - BZDs, 2022Coste - Clonazepam (Mixed indications), 2020Freeman - BZDs, 2018Ogawa - BZDs, 2018Yonkers - BZDs, 2017Kilic - Clonazepam (Mixed indications), 2014Källén - BZDs, 2013Hironaka - BZDs (Control exposed to Atypical antipsy), 2011Hironaka - BZDs (Control unexposed, disease free), 2011Hironaka - BZDs (Control unexposed, sick), 2011Calderon-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 R83653	Li, 2026	Preterm birth	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Not specified	1.20 [1.18;1.23]	7,271/54,892   74,129/384,391	81,400	54,892		ref
S15397 R63466	Chan - BZDs, 2023	Preterm birth (<37 gestational weeks)	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)	1.19 [1.00;1.42]	142/1,060   44,207/531,164	44,349	1,060		ref
S17870 R75496	Delteil - BZDs (Controls unexposed, NOS), 2023	Preterm birth (<37 GW)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	1.52 [1.32;1.74] C excluded (control group)	235/2,517   5,217/82,163	5,452	2,517		ref
S15610 R75488	Delteil - BZDs (Controls unexposed, sick), 2023	Preterm birth (<37 GW)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: No BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	1.28 [0.99;1.65] C	235/2,517   88/1,180	323	2,517		ref
S17848 R75324	Meng - BZDs (Controls unexposed, sibling), 2023	Preterm birth (<37 weeks’ gestation)	early pregnancy	population based cohort retrospective	sibling excluded	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	0.93 [0.86;0.99] excluded (control group)	-/-   -/-	-	-		ref
S15409 R63480	Meng - BZDs (Controls unexposed, sick), 2023	Preterm birth (<37 weeks’ gestation)	early pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	1.17 [1.14;1.20]	6,021/61,218   235,053/2,776,683	241,074	61,218		ref
S15405 R63474	Lee - Alprazolam, 2022	Preterm birth (< 37 weeks)	1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Not specified	2.27 [0.92;5.60]	7/82   22/579	29	82		ref
S15446 R63532	Zanisi - BZDs, 2022	Premature birth	during pregnancy (anytime or not specified)	cohort	unexposed (general population or NOS)	Adjustment: No BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications)	2.24 [0.85;5.90]	-/-   -/-	-	-		ref
S15584 R64105	Coste - Clonazepam (Mixed indications), 2020	Gestational age at birth (< 37 WA)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No BZD Coexposure: No (among antiseizure medications)	1.43 [1.16;1.77] C	93/1,246   91,255/1,710,441	91,348	1,246		ref
S15319 R63027	Freeman - BZDs, 2018	Premature (< 37 weeks)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications) Indication BZD: Psychiatric diseases (depression, anxiety, ...)	1.31 [0.55;2.32]	17/144   87/650	104	144		ref
S15533 R63799	Ogawa - BZDs, 2018	Preterm birth (less than 37 completed weeks)	2nd and/or 3rd trimester	nested case control	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Yes (with psychiatric (ATD and/or psychotropics) medications)	2.03 [1.11;3.69]	-/-   746/-	-	-		ref
S15314 R63007	Yonkers - BZDs, 2017	Preterm Birth (before 36 completed weeks of gestation (36 weeks and 6 days))	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...)	1.98 [0.97;4.04]	12/67   -/-	-	67		ref
S15315 R63013	Kilic - Clonazepam (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: No (among antiseizure medications)	1.60 [1.00;2.40]	23/262   33,974/676,834	33,997	262		ref
S15587 R64163	Källén - BZDs, 2013	Preterm birth (<37 weeks)	2nd and/or 3rd trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: Not specified	1.62 [1.37;1.91]	157/-   -/-	-	-		ref
S17712 R74712	Hironaka - BZDs (Control exposed to Atypical antipsy), 2011	Preterm birth (NOS)	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...)	1.89 [0.03;112.07] C excluded (control group)	0/5   0/9	0	5		ref
S17710 R74700	Hironaka - BZDs (Control unexposed, disease free), 2011	Preterm birth (NOS)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free excluded	Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...)	12.24 [0.51;293.29] C excluded (control group)	0/5   2/278	2	5		ref
S17711 R74706	Hironaka - BZDs (Control unexposed, sick), 2011	Preterm birth (NOS)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No BZD Coexposure: Not specified Indication BZD: Psychiatric diseases (depression, anxiety, ...)	0.56 [0.01;37.57] C	0/5   0/3	0	5		ref
S15320 R63032	Calderon-Margalit - BZDs, 2009	Preterm delivery (before 37 weeks of gestation)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: No (among psychiatric (ATD and/or psychotropics) medications)	5.56 [2.71;11.40]	20/43   234/2,493	254	43		ref
					Total	14 studies	1.30 [1.22;1.40]		492,878	121,536
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 17712, 17710, 17870, 17848

Umbrella review (other published meta-analyses)