Acetaminophen (Paracetamol) updated on 09-20-2024

Cognitive developmental disorders/delay (3-6 years old)

id	Study   Auto Okubo (Controls unexposed, general population), 2025Okubo (Controls unexposed, sibling), 2025Liew a, 2016	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.
S18555 R78894	Okubo (Controls unexposed, general population), 2025	Intellectual Disability (ID) - ICD-10 codes (F70-F79 - diagnoses only) - Mean follow up 4.4 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Paracetamol use: prescription or medical files	1.03 [0.90;1.16]	-/42,123   -/42,123	-	42,123		ref
S18556 R78901	Okubo (Controls unexposed, sibling), 2025	Intellectual Disability (ID) - ICD-10 codes (diagnoses only) - Mean follow up 4.4 years	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	sibling excluded	Adjustment: Yes Control group: Sibling Paracetamol use: prescription or medical files	0.72 [0.45;1.15] excluded (control group)	-/11,696   -/11,897	-	11,696		ref
S16642 R69843	Liew a, 2016	Full-scale IQ - Wechsler Primary and Preschool Scales of intelligence-revised (WPPSi-r) - 5 years old	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes extrapolated (cont. endpoint) Paracetamol use: maternal ITW/questionnaires during pregnancy	1.16 [0.96;1.40]	-/881   -/610	-	881		ref
					Total	2 studies	1.07 [0.96;1.19]		0	43,004
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 18556

Umbrella review (other published meta-analyses)