Acetaminophen (Paracetamol) updated on 09-20-2024

ADHD (Attention deficit hyperactivity disorder): Diagnosis

id	Study   Auto Okubo (Controls unexposed, general population), 2025Okubo (Controls unexposed, sibling), 2025Pleau, 2025Ahlqvist (Population-Based), 2024Ahlqvist (Sibling), 2024Chen, 2019Ystrom or Gustavson (Gustavson 2021 - Sibling), 2017Ystrom or Gustavson (Ystrom - Population-Based), 2017Liew, 2014	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 R78889	Okubo (Controls unexposed, general population), 2025	Attention-deficit hyperactivity disorder (ADHD) - ICD-10 codes (F90 - diagnoses only or ADHD's medications) - 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	1.22 [1.06;1.41]	-/42,123   -/42,123	-	42,123		ref
S18556 R78896	Okubo (Controls unexposed, sibling), 2025	Attention-deficit hyperactivity disorder (ADHD) - ICD-10 codes (diagnoses only or ADHD's medications) - 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	0.86 [0.52;1.44] excluded (control group)	-/11,696   -/11,897	-	11,696		ref
S18664 R79317	Pleau, 2025	Attention-deficit/hyperactivity disorder (ADHD) - (1) at least two dates with a diagnostic code of ADHD ; (2) at least two dates with a filled prescription for an ADHD medication or (3) at least one diagnosis of ADHD and one filled prescription for an ADHD medication - At least 2 years	2nd and/or 3rd trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Paracetamol use: prescription or medical files	1.09 [0.94;1.27]	208/1,827   12,788/176,993	12,996	1,827		ref
S16629 R69722	Ahlqvist (Population-Based), 2024	Attention-deficit/hyperactivity disorder (ADHD) - ICD-10 (F90) or ICD-9 (314) - Median (IQR) follow-up of 13.4 (7.6-19.8) years	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy	1.07 [1.05;1.10]	12,834/185,909   133,552/2,294,888	146,386	185,909		ref
S16630 R69728	Ahlqvist (Sibling), 2024	Attention-deficit/hyperactivity disorder (ADHD) - ICD-10 (F90) or ICD-9 (314) - Median (IQR) follow-up of 13.4 (7.6-19.8) years	during pregnancy (anytime or not specified)	population based cohort retrospective	sibling excluded	Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy	0.98 [0.94;1.02] excluded (control group)	8,526/-   87,679/-	96,205	-		ref
S16639 R69757	Chen, 2019	Diagnoses of ADHD (ICD-9-CM code: 314) by board-certified psychiatrists on the basis of diagnostic interviews and clinical judgement - Age 0 - 15 years old (mean diagnosis 3.71)	during pregnancy (anytime or not specified)	nested case control	unexposed (general population or NOS)	Adjustment: Yes Paracetamol use: prescription or medical files	1.20 [1.01;1.42]	676/3,236   274/1,514	950	3,236		ref
S16655 R69967	Ystrom or Gustavson (Gustavson 2021 - Sibling), 2017	Attention deficit hyperactivity disorder - ICD-10 code F90 - Between 0 and 18 years old (Exposed >28 days)	during pregnancy (anytime or not specified)	prospective cohort	sibling excluded	Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy	2.02 [1.17;3.25] excluded (control group)	-/469   -/12,080	-	469		ref
S16651 R69922	Ystrom or Gustavson (Ystrom - Population-Based), 2017	Attention-deficit/hyperactivity (ADHD - diagnosis of hyperkinetic disorder (F90.0, F90.1, F90.8, or F90.9)) - At 3-15 years old.	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy	1.12 [1.02;1.24]	-/52,707   -/60,266	-	52,707		ref
S16641 R69813	Liew, 2014	Hyperkinetic disorder diagnosis (ICD-10: F90.0-F90.9) - Mean age of children at the end of follow-up: 10.7 years (range, 8.2-13.4 years)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy	1.37 [1.19;1.59]	551/36,187   283/28,135	834	36,187		ref
					Total	6 studies	1.16 [1.07;1.25]		161,166	321,989
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 16655, 16630, 18556

Umbrella review (other published meta-analyses)