Acetaminophen (Paracetamol) updated on 09-20-2024

All congenital malformations (majors, minors, majors and minors, or unspecified)

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
R79826		 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
R79827		 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
S18496
R78615		 Xu, 2024 Congenital disabilities during pregnancy (anytime or not specified) excluded retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: prescription or medical files 0.70 [0.41;1.17]
excluded (exposition period) 		26/501   37/501 63 501
ref
S18630
R79319		 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
R79320		 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
S18595
R78997		 Thulstrup, 1999 Malformations (ICD-8 or ICD-10) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Paracetamol use: prescription or medical files 2.28 [0.97;5.36] 6/55   697/13,327 703 55
ref
S18536
R78726		 Aselton, 1985 Any congenital disorders (malformations) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Paracetamol use: prescription or medical files 0.34 [0.08;1.38] C 2/350   103/6,159 105 350
ref
S18776
R79889		 Nelson, 1971 All 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 0.88 [0.27;2.88] C 4/13   454/1,356 458 13
ref
Total 6 studies 1.09 [0.93;1.29] 64,594 39,950
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]1,0308,59028%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Poletta, 2012Poletta, 2012 1.25[1.17; 1.33]58,5144,51833%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: unclear Rebordosa a, 2008Rebordosa a, 2008 1.01[0.93; 1.08]3,78426,42432%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Thulstrup, 1999Thulstrup, 1999 2.28[0.97; 5.36]703553%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Aselton, 1985Aselton, 1985 0.34[0.08; 1.38]1053501%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Nelson, 1971Nelson, 1971 0.88[0.27; 2.88]458132%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Total (6 studies) I2 = 82% 1.09[0.93; 1.29]64,59439,9500.25.01.0ROB: 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 1.02[0.88; 1.18]5,62235,41949%NABroe (Controls unexposed, sick), 2025 Rebordosa a, 2008 Thulstrup, 1999 Aselton, 1985 4 case control studiescase control studies 1.25[1.17; 1.32]58,9724,5310%NAPoletta, 2012 Nelson, 1971 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.13[0.92; 1.39]63,56431,36083%NAPoletta, 2012 Rebordosa a, 2008 Thulstrup, 1999 Aselton, 1985 Nelson, 1971 5 unexposed, sickunexposed, sick 1.00[0.87; 1.15]1,0308,590 -NABroe (Controls unexposed, sick), 2025 1 Tags Adjustment   - No  - No 0.94[0.49; 1.81]59,0774,88145%NAPoletta, 2012 Aselton, 1985 Nelson, 1971 3   - Yes  - Yes 1.02[0.91; 1.15]5,51735,06943%NABroe (Controls unexposed, sick), 2025 Rebordosa a, 2008 Thulstrup, 1999 3 MatchedMatched 0.88[0.27; 2.88]45813 -NANelson, 1971 1 Paracetamol use   - maternal ITW/questionnaires after p ...  - maternal ITW/questionnaires after pregnancy 1.25[1.17; 1.32]58,9724,5310%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 1.04[0.60; 1.80]2,2969,00849%NABroe (Controls unexposed, sick), 2025 Thulstrup, 1999 Aselton, 1985 Nelson, 1971 4 All studiesAll studies 1.09[0.93; 1.29]64,59439,95082%NABroe (Controls unexposed, sick), 2025 Poletta, 2012 Rebordosa a, 2008 Thulstrup, 1999 Aselton, 1985 Nelson, 1971 60.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.80.8590.000Broe (Controls unexposed, sick), 2025Poletta, 2012Rebordosa a, 2008Thulstrup, 1999Aselton, 1985Nelson, 1971

Asymetry test p-value = 0.6566 (by Egger's regression)

slope=0.1530 (0.0837); intercept=-0.7222 (1.5063); t=0.4795; p=0.6566

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) 1.13[0.97; 1.30]80,87639,95079%NABroe (Controls unexposed, general pop), 2025 Poletta, 2012 Rebordosa a, 2008 Thulstrup, 1999 Aselton, 1985 Nelson, 1971 6 unexposed, sick controlsunexposed, sick controls 1.00[0.87; 1.15]1,0308,590 -NABroe (Controls unexposed, sick), 2025 10.510.01.0