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

ASD (Autism spectrum disorder): Diagnosis/Risk

id	Study   Auto Chan - BZDs, 2023Bjørk - Clonazepam (Mixed indications), 2022Chen - BZDs (Controls unexposed, NOS), 2022Chen - BZDs (Controls unexposed, sibling), 2022Chen - BZDs (Controls unexposed, sick), 2022Coste - Clonazepam (Mixed indications), 2020	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 trimester	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.
S15397 R64487	Chan - BZDs, 2023	Autism spectrum disorder (ASD) - ICD-9-CM: 299 - Median follow-up time of 8.76 years	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)	1.42 [1.06;1.90]	-/-   -/-	-	-		ref
S15459 R63565	Bjørk - Clonazepam (Mixed indications), 2022	Diagnosis autism spectrum disorder (ASD): childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) - Median follow up clonazepam 9.5 (5.5-13.9) years old	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: No (among antiseizure medications)	1.43 [0.96;2.12]	25/1,182   38,437/4,463,879	38,462	1,182		ref
S15460 R64488	Chen - BZDs (Controls unexposed, NOS), 2022	Autism spectrum disorder ASD (ICD-9 code 299; ICD-10 code F84) - At mean 8.5 (3.2) years.	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes BZD Coexposure: Not specified	0.96 [0.89;1.03] excluded (control group)	754/70,451   13,276/1,440,435	14,030	70,451		ref
S15638 R64544	Chen - BZDs (Controls unexposed, sibling), 2022	Autism spectrum disorder ASD (ICD-9 code 299; ICD-10 code F84) - At mean 8.5 (3.2) years.	1st trimester	retrospective cohort (claims database)	sibling excluded	Adjustment: Yes BZD Coexposure: Not specified	0.92 [0.75;1.14] excluded (control group)	-/26,652   -/29,233	-	26,652		ref
S17008 R71239	Chen - BZDs (Controls unexposed, sick), 2022	Autism spectrum disorder ASD (ICD-9 code 299; ICD-10 code F84) - At mean 8.5 (3.2) years.	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes BZD Coexposure: Not specified	0.72 [0.60;0.87]	-/8,492   -/30,832	-	8,492		ref
S15584 R64119	Coste - Clonazepam (Mixed indications), 2020	Diagnosis Pervasive developmental disorders (F84) - Mean age follow-up 4.4 years old	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes BZD Coexposure: No (among antiseizure medications)	1.10 [0.50;2.10]	8/1,246   4,280/1,710,441	4,288	1,246		ref
					Total	4 studies	1.11 [0.72;1.72]		42,750	10,920
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 15460, 15638

Umbrella review (other published meta-analyses)