Acetaminophen (Paracetamol) updated on 09-20-2024

Preterm (< 37 weeks)

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.
S18581
R78964		 Andreasen, 2025 Preterm (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Paracetamol use: maternal ITW/questionnaires during pregnancy 1.13 [0.66;1.92] C 43/1,106   21/608 64 1,106
ref
S18496
R78609		 Xu, 2024 Preterm birth (<37 gestation weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: prescription or medical files 1.07 [0.68;1.68] 47/501   42/501 89 501
ref
S18594
R78994		 De Castro, 2022 Preterm birth (birth before 37 completed weeks of gestation) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.02 [0.47;2.01] 11/106   70/654 81 106
ref
S18577
R78942		 Killion, 2022 Preterm birth - Cumulative acetaminophen use at 32 weeks 5th quintile during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.20 [0.81;1.78] 42/269   49/473 91 269
ref
S16647
R69890		 Sznajder, 2022 Preterm (< 37 gestational weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Paracetamol use: maternal ITW/questionnaires during pregnancy 1.00 [0.65;1.53] C 38/1,011   53/1,411 91 1,011
ref
S18513
R78655		 Zafeiri, 2022 Premature delivery (< 37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.56 [1.48;1.65] 2,510/24,099   6,264/107,143 8,774 24,099
ref
S18542
R78802		 Arneja, 2020 Preterm birth throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.29 [0.58;2.88] 20/135   96/294 116 135
ref
S18546
R78826		 Rebordosa, 2009 All preterm (<37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.01 [0.93;1.10] 967/-   1,225/- 2,192 -
ref
S18610
R79203		 Czeizel, 2005 Preterm birth was (<37 completed weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires after pregnancy 0.40 [0.20;0.80] 6/173   3,490/37,978 3,496 173
ref
S18595
R78999		 Thulstrup, 1999 Preterm delivery (< 37 weeks) 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Paracetamol use: prescription or medical files 0.59 [0.22;1.61] 4/111   793/13,327 797 111
ref
Total 10 studies 1.05 [0.82;1.33] 15,791 27,511
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 Andreasen, 2025Andreasen, 2025 1.13[0.66; 1.92]641,1069%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Xu, 2024Xu, 2024 1.07[0.68; 1.68]8950111%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: criticalROB mesure: moderateROB reporting: moderate De Castro, 2022De Castro, 2022 1.02[0.47; 2.01]811067%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Killion, 2022Killion, 2022 1.20[0.81; 1.78]9126912%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Sznajder, 2022Sznajder, 2022 1.00[0.65; 1.53]911,01111%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Zafeiri, 2022Zafeiri, 2022 1.56[1.48; 1.65]8,77424,09917%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Arneja, 2020Arneja, 2020 1.29[0.58; 2.88]1161356%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Rebordosa, 2009Rebordosa, 2009 1.01[0.93; 1.10]2,192-17%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Czeizel, 2005Czeizel, 2005 0.40[0.20; 0.80]3,4961737%ROB confusion: unclearROB selection: unclearROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: critical Thulstrup, 1999Thulstrup, 1999 0.59[0.22; 1.61]7971114%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (10 studies) I2 = 90% 1.05[0.82; 1.33]15,79127,5110.25.01.0ROB: 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 1.05[0.82; 1.33]15,79127,51190%NAAndreasen, 2025 Xu, 2024 De Castro, 2022 Killion, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 10 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.02[0.79; 1.33]15,70027,24291%NAAndreasen, 2025 Xu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 9 unexposed, sickunexposed, sick 1.20[0.81; 1.78]91269 -NAKillion, 2022 1 Tags Adjustment   - No  - No 1.05[0.75; 1.46]1552,1170%NAAndreasen, 2025 Sznajder, 2022 2   - Yes  - Yes 1.04[0.79; 1.37]15,63625,39492%NAXu, 2024 De Castro, 2022 Killion, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 8 Paracetamol use   - maternal ITW/questionnaires after p ...  - maternal ITW/questionnaires after pregnancy 0.40[0.20; 0.80]3,496173 -NACzeizel, 2005 1   - maternal ITW/questionnaires during ...  - maternal ITW/questionnaires during pregnancy 1.18[0.91; 1.53]11,40926,72692%NAAndreasen, 2025 De Castro, 2022 Killion, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 7   - prescription or medical files  - prescription or medical files 0.94[0.59; 1.52]88661212%NAXu, 2024 Thulstrup, 1999 2 All studiesAll studies 1.05[0.82; 1.33]15,79127,51190%NAAndreasen, 2025 Xu, 2024 De Castro, 2022 Killion, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 100.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.21.20.6090.000Andreasen, 2025Xu, 2024De Castro, 2022Killion, 2022Sznajder, 2022Zafeiri, 2022Arneja, 2020Rebordosa, 2009Czeizel, 2005Thulstrup, 1999

Asymetry test p-value = 0.1742 (by Egger's regression)

slope=0.3799 (0.0868); intercept=-1.8070 (1.2115); t=1.4915; p=0.1742

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) 1.02[0.79; 1.33]15,70027,24291%NAAndreasen, 2025 Xu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 9 unexposed, sick controlsunexposed, sick controls 1.20[0.81; 1.78]91269 -NAKillion, 2022 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Castro (Preterm birth (delivery <37 weeks of ...Castro (Preterm birth (delivery <37 weeks of gestational age)) 0.72[0.20; 2.59]99%-Wwhatever (meta-analysis)T33rd trimesterstudies TTT5 Castro (Preterm birth (delivery <37 weeks of ...Castro (Preterm birth (delivery <37 weeks of gestational age)) 0.97[0.59; 1.58]96%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT6 Castro (Preterm birth (delivery <37 weeks of ...Castro (Preterm birth (delivery <37 weeks of gestational age) (high quality studies)) 0.94[0.54; 1.65]97%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 metaPregmetaPreg 1.05[0.82; 1.33]90%27,511----Andreasen, 2025 Xu, 2024 De Castro, 2022 Killion, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 100.510.01.0