Acetaminophen_Exposure/effect relationship (metaPreg)

ADHD (Attention deficit hyperactivity disorder): Diagnosis

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S16484
R68878		 Ahlqvist_High exposure, 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) Acetaminophen: high exposure 1.17 [1.08;1.27] -/-   -/- - -
ref
S16474
R68742		 Ahlqvist_Low exposure, 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) Acetaminophen: low exposure 1.14 [1.06;1.23] -/-   -/- - -
ref
S16483
R68876		 Ahlqvist_Medium exposure, 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) Acetaminophen: medium exposure 1.25 [1.18;1.33] -/-   -/- - -
ref
S16488
R68886		 Ystrom_High dose, 2017 Attention-deficit/hyperactivity (ADHD - diagnosis of hyperkinetic disorder (F90.0, F90.1, F90.8, or F90.9)) - At 3-15 years old. > 28 days during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Acetaminophen: high exposure 2.20 [1.50;3.24] -/-   -/- - -
ref
S16477
R68759		 Ystrom_Low dose, 2017 Attention-deficit/hyperactivity (ADHD - diagnosis of hyperkinetic disorder (F90.0, F90.1, F90.8, or F90.9)) - At 3-15 years old. 1–7 days during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Acetaminophen: low exposure 0.90 [0.81;1.00] -/-   -/- - -
ref
S16487
R68884		 Ystrom_Medium dose, 2017 Attention-deficit/hyperactivity (ADHD - diagnosis of hyperkinetic disorder (F90.0, F90.1, F90.8, or F90.9)) - At 3-15 years old. 8–28 days during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Acetaminophen: medium exposure 1.24 [1.06;1.44] -/-   -/- - -
ref
S16486
R68882		 Liew_High exposure, 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) - > 6 weeks during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Acetaminophen: high exposure 1.73 [1.44;2.06] 148/-   283/28,135 431 -
ref
S16480
R68786		 Liew_Low exposure, 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) - 1 week during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Acetaminophen: low exposure 1.30 [1.05;1.61] 128/-   283/28,135 411 -
ref
S16485
R68880		 Liew_Medium exposure, 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) - 2-5 weeks during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Acetaminophen: medium exposure 1.19 [0.95;1.48] 115/-   283/28,135 398 -
ref
Total 9 studies 1.25 [1.12;1.39] 1,240 0
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

StudyTE95% CIn casesn exposedweightROBABCDEF Ahlqvist_High exposure, 2024Ahlqvist_High exposure, 2024 1.17[1.08; 1.27]--14%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ahlqvist_Low exposure, 2024Ahlqvist_Low exposure, 2024 1.14[1.06; 1.23]--14%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ahlqvist_Medium exposure, 2024Ahlqvist_Medium exposure, 2024 1.25[1.18; 1.33]--14%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ystrom_High dose, 2017Ystrom_High dose, 2017 2.20[1.50; 3.24]--5%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ystrom_Low dose, 2017Ystrom_Low dose, 2017 0.90[0.81; 1.00]--13%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ystrom_Medium dose, 2017Ystrom_Medium dose, 2017 1.24[1.06; 1.44]--11%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Liew_High exposure, 2014Liew_High exposure, 2014 1.73[1.44; 2.06]431-10%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Liew_Low exposure, 2014Liew_Low exposure, 2014 1.30[1.05; 1.61]411-9%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Liew_Medium exposure, 2014Liew_Medium exposure, 2014 1.19[0.95; 1.48]398-9%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (9 studies) I2 = 86% 1.25[1.12; 1.39]1,240-0.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.25[1.12; 1.39]1,240-86%NAAhlqvist_High exposure, 2024 Ahlqvist_Low exposure, 2024 Ahlqvist_Medium exposure, 2024 Ystrom_High dose, 2017 Ystrom_Low dose, 2017 Ystrom_Medium dose, 2017 Liew_High exposure, 2014 Liew_Low exposure, 2014 Liew_Medium exposure, 2014 9 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.25[1.12; 1.39]1,240-86%NAAhlqvist_High exposure, 2024 Ahlqvist_Low exposure, 2024 Ahlqvist_Medium exposure, 2024 Ystrom_High dose, 2017 Ystrom_Low dose, 2017 Ystrom_Medium dose, 2017 Liew_High exposure, 2014 Liew_Low exposure, 2014 Liew_Medium exposure, 2014 9 Tags Acetaminophen   - high exposure  - high exposure 1.59[1.11; 2.28]431-91%NAAhlqvist_High exposure, 2024 Ystrom_High dose, 2017 Liew_High exposure, 2014 3   - low exposure  - low exposure 1.09[0.89; 1.32]411-88%NAAhlqvist_Low exposure, 2024 Ystrom_Low dose, 2017 Liew_Low exposure, 2014 3   - medium exposure  - medium exposure 1.25[1.18; 1.31]398-0%NAAhlqvist_Medium exposure, 2024 Ystrom_Medium dose, 2017 Liew_Medium exposure, 2014 3 All studiesAll studies 1.25[1.12; 1.39]1,240-86%NAAhlqvist_High exposure, 2024 Ahlqvist_Low exposure, 2024 Ahlqvist_Medium exposure, 2024 Ystrom_High dose, 2017 Ystrom_Low dose, 2017 Ystrom_Medium dose, 2017 Liew_High exposure, 2014 Liew_Low exposure, 2014 Liew_Medium exposure, 2014 90.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-0.90.90.2360.000Ahlqvist_High exposure, 2024Ahlqvist_Low exposure, 2024Ahlqvist_Medium exposure, 2024Ystrom_High dose, 2017Ystrom_Low dose, 2017Ystrom_Medium dose, 2017Liew_High exposure, 2014Liew_Low exposure, 2014Liew_Medium exposure, 2014

Asymetry test p-value = 0.3510 (by Egger's regression)

slope=0.0820 (0.1014); intercept=1.9009 (1.9025); t=0.9991; p=0.3510

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.25[1.12; 1.39]1,240-86%NAAhlqvist_High exposure, 2024 Ahlqvist_Low exposure, 2024 Ahlqvist_Medium exposure, 2024 Ystrom_High dose, 2017 Ystrom_Low dose, 2017 Ystrom_Medium dose, 2017 Liew_High exposure, 2014 Liew_Low exposure, 2014 Liew_Medium exposure, 2014 90.510.01.0