Acetaminophen (Paracetamol) updated on 09-20-2024

Major congenital malformations

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.
S18507
R78640		 Broe (Controls unexposed, general pop), 2025 Major congenital malformations (exclusion of chromosomal abnormalities (ICD-10 codes Q90– Q99)) 1st trimester population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Paracetamol use: prescription or medical files 1.12 [1.01;1.26]
excluded (control group) 		384/8,590   16,928/471,855 17,312 8,590
ref
S18508
R78641		 Broe (Controls unexposed, sick), 2025 Major congenital malformations (exclusion of chromosomal abnormalities (ICD-10 codes Q90– Q99)) 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes Paracetamol use: prescription or medical files 1.00 [0.87;1.15] 384/8,590   646/14,817 1,030 8,590
ref
S18630
R79168		 Poletta, 2012 Single or multiple birth defects (excluding minor anomalies and syndromes) 1st trimester case control unexposed (general population or NOS) Adjustment: No Paracetamol use: maternal ITW/questionnaires after pregnancy 1.25 [1.17;1.33] C 1,788/4,518   56,726/164,810 58,514 4,518
ref
S18505
R78735		 Rebordosa a, 2008 Major congenital abnormalities 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.01 [0.93;1.08] 1,132/26,424   2,652/61,718 3,784 26,424
ref
S18776
R79890		 Nelson, 1971 Major abnormalities 1st trimester case control unexposed (general population or NOS) Adjustment: No Matched Paracetamol use: maternal ITW/questionnaires after pregnancy Paracetamol use: prescription or medical files 1.16 [0.25;5.41] C 2/11   173/1,075 175 11
ref
Total 4 studies 1.09 [0.93;1.27] 63,503 39,543
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 Broe (Controls unexposed, sick), 2025Broe, 2025 1 1.00[0.87; 1.15]1,0308,59029%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Poletta, 2012Poletta, 2012 1.25[1.17; 1.33]58,5144,51836%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: unclear Rebordosa a, 2008Rebordosa a, 2008 1.01[0.93; 1.08]3,78426,42435%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Nelson, 1971Nelson, 1971 1.16[0.25; 5.41]175111%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Total (4 studies) I2 = 86% 1.09[0.93; 1.27]63,50339,5430.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.01[0.94; 1.08]4,81435,0140%NABroe (Controls unexposed, sick), 2025 Rebordosa a, 2008 2 case control studiescase control studies 1.25[1.17; 1.33]58,6894,5290%NAPoletta, 2012 Nelson, 1971 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.12[0.92; 1.37]62,47330,95389%NAPoletta, 2012 Rebordosa a, 2008 Nelson, 1971 3 unexposed, sickunexposed, sick 1.00[0.87; 1.15]1,0308,590 -NABroe (Controls unexposed, sick), 2025 1 Tags Adjustment   - No  - No 1.25[1.17; 1.33]58,6894,5290%NAPoletta, 2012 Nelson, 1971 2   - Yes  - Yes 1.01[0.94; 1.08]4,81435,0140%NABroe (Controls unexposed, sick), 2025 Rebordosa a, 2008 2 MatchedMatched 1.16[0.25; 5.41]17511 -NANelson, 1971 1 Paracetamol use   - maternal ITW/questionnaires after p ...  - maternal ITW/questionnaires after pregnancy 1.25[1.17; 1.33]58,6894,5290%NAPoletta, 2012 Nelson, 1971 2   - maternal ITW/questionnaires during ...  - maternal ITW/questionnaires during pregnancy 1.01[0.94; 1.09]3,78426,424 -NARebordosa a, 2008 1   - prescription or medical files  - prescription or medical files 1.00[0.87; 1.15]1,2058,6010%NABroe (Controls unexposed, sick), 2025 Nelson, 1971 2 All studiesAll studies 1.09[0.93; 1.27]63,50339,54386%NABroe (Controls unexposed, sick), 2025 Poletta, 2012 Rebordosa a, 2008 Nelson, 1971 40.55.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.81.90.9430.000Broe (Controls unexposed, sick), 2025Poletta, 2012Rebordosa a, 2008Nelson, 1971

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18507

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.12[0.98; 1.29]79,78539,54384%NABroe (Controls unexposed, general pop), 2025 Poletta, 2012 Rebordosa a, 2008 Nelson, 1971 4 unexposed, sick controlsunexposed, sick controls 1.00[0.87; 1.15]1,0308,590 -NABroe (Controls unexposed, sick), 2025 10.510.01.0