Acetaminophen (Paracetamol) updated on 09-20-2024

Low birth weight (< 2500g)

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.
S18496
R78613		 Xu, 2024 Low birth weight (<2500 g) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: prescription or medical files 0.92 [0.54;1.55] 31/501   33/501 64 501
ref
S18594
R78995		 De Castro, 2022 Low birth weight (birth weight of less than 2500 g) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 0.21 [0.01;0.99] 1/106   33/654 34 106
ref
S16647
R69891		 Sznajder, 2022 Low birth weigh (< 2500 grams) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Paracetamol use: maternal ITW/questionnaires during pregnancy 0.94 [0.57;1.54] C 27/1,011   40/1,411 67 1,011
ref
S18513
R78658		 Zafeiri, 2022 Low Birth Weight (≤2499 g) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.60 [1.51;1.69] 2,213/24,096   5,910/107,109 8,123 24,096
ref
S18542
R79220		 Arneja, 2020 Low birthweight (birthweight of less than 2500 g) throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.18 [0.47;2.95] 19/125   88/272 107 125
ref
S18546
R78824		 Rebordosa, 2009 Low birth weight (<2500g) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires during pregnancy 1.11 [0.94;1.31] 622/-   749/- 1,371 -
ref
S18610
R79204		 Czeizel, 2005 Low birthweight (< 2500g) during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: Yes Paracetamol use: maternal ITW/questionnaires after pregnancy 0.70 [0.30;1.40] 7/173   2,161/37,978 2,168 173
ref
S18595
R78998		 Thulstrup, 1999 Low birth weight (<2500 g) 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Paracetamol use: prescription or medical files 1.05 [0.25;4.31] 2/111   209/13,327 211 111
ref
Total 8 studies 1.10 [0.83;1.45] 12,145 26,123
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 Xu, 2024Xu, 2024 0.92[0.54; 1.55]6450114%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: criticalROB mesure: moderateROB reporting: moderate De Castro, 2022De Castro, 2022 0.21[0.01; 0.99]341061%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Sznajder, 2022Sznajder, 2022 0.94[0.57; 1.54]671,01115%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Zafeiri, 2022Zafeiri, 2022 1.60[1.51; 1.69]8,12324,09627%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Arneja, 2020Arneja, 2020 1.18[0.47; 2.95]1071257%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Rebordosa, 2009Rebordosa, 2009 1.11[0.94; 1.31]1,371-25%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Czeizel, 2005Czeizel, 2005 0.70[0.30; 1.40]2,1681739%ROB confusion: unclearROB selection: unclearROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: critical Thulstrup, 1999Thulstrup, 1999 1.05[0.25; 4.31]2111113%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 78% 1.10[0.83; 1.45]12,14526,1230.25.01.0ROB: 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 1.10[0.83; 1.45]12,14526,12378%NAXu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.10[0.83; 1.45]12,14526,12378%NAXu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 8 Tags Adjustment   - No  - No 0.94[0.57; 1.54]671,011 -NASznajder, 2022 1   - Yes  - Yes 1.13[0.84; 1.52]12,07825,11278%NAXu, 2024 De Castro, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 7 Paracetamol use   - maternal ITW/questionnaires after p ...  - maternal ITW/questionnaires after pregnancy 0.70[0.32; 1.51]2,168173 -NACzeizel, 2005 1   - maternal ITW/questionnaires during ...  - maternal ITW/questionnaires during pregnancy 1.20[0.88; 1.64]9,70225,33883%NADe Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 5   - prescription or medical files  - prescription or medical files 0.93[0.57; 1.53]2756120%NAXu, 2024 Thulstrup, 1999 2 All studiesAll studies 1.10[0.83; 1.45]12,14526,12378%NAXu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 80.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.82.81.4070.000Xu, 2024De Castro, 2022Sznajder, 2022Zafeiri, 2022Arneja, 2020Rebordosa, 2009Czeizel, 2005Thulstrup, 1999

Asymetry test p-value = 0.0194 (by Egger's regression)

slope=0.4998 (0.0460); intercept=-1.9215 (0.6067); t=3.1671; p=0.0194

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) 1.10[0.83; 1.45]12,14526,12378%NAXu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 80.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Castro (Low birth weight (birthweight <2500 g))Castro (Low birth weight (birthweight <2500 g)) Out of scale0.46[0.13; 1.67]95%-Wwhatever (meta-analysis)T33rd trimesterstudies TTT3 Castro (Low birth weight (birthweight <2500 g))Castro (Low birth weight (birthweight <2500 g)) 0.65[0.59; 0.72]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 Castro (Low birth weight (birthweight <2500 g ...Castro (Low birth weight (birthweight <2500 g) (high quality studies)) 0.65[0.59; 0.72]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 1.10[0.83; 1.45]78%26,123----Xu, 2024 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Arneja, 2020 Rebordosa, 2009 Czeizel, 2005 Thulstrup, 1999 80.510.01.0