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Acetaminophen (Paracetamol)
Overall results
Study description
Excluded studies
Table
Graphic
auto
during pregnancy (anytime or not specified)
1st trimester
2nd trimester
3rd trimester
2nd and/or 3rd trimester
throughout pregnancy
early pregnancy
days before delivery
late pregnancy
preconception-only
periconceptional
preconceptional for kinetic reason
at least 1st trimester
3 months (or more) before pregnancy or during pregnancy
1st and 2nd trimester
3 months or more before pregnancy or1st trimester
Paternal exp. genotoxic window only (0–3 months preconception)
Paternal exposure: epigenetic window only (3–xxx months preconception)
Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)
Paternal exposure: other window
Whatever the period exposition
individual studies
Outcome
TE
95% CI
n cases
n exposed
k
Pub. bias
Congenital malformations
Gastroschisis
Werler, 1992 Torfs, 1996 Werler, 2002 Rebordosa a, 2008 Feldkamp, 2010 Robledo-Aceves, 2015 Given, 2017
7
1.21
[
0.97
; 1.51]
961
31,313
not evaluable
All congenital malformations (majors, minors, majors and minors, or unspecified)
Nelson, 1971 Aselton, 1985 Thulstrup, 1999 Rebordosa a, 2008 Poletta, 2012 Broe (Controls unexposed, sick), 2025
6
1.09
[
0.93
; 1.29]
64,594
39,950
not evaluable
Composite criterion: malformations of the genital system (cryptorchidism or hypospadias or clitoral hypertrophy or labial fusion, …)
Rebordosa a, 2008 Jensen, 2010 Kristensen, 2011 Snijder, 2012 Lind, 2013 Fisher, 2016 Zafeiri, 2022
7
0.98
[
0.88
; 1.08]
2,838
42,634
not evaluable
Cryptorchidism / Undescended testicle (minor malformation)
Jensen, 2010 Kristensen, 2011 Snijder, 2012 Fisher, 2016 Zafeiri, 2022
5
1.04
[
0.88
; 1.23]
1,114
12,808
not evaluable
Major congenital malformations
Nelson, 1971 Rebordosa a, 2008 Poletta, 2012 Broe (Controls unexposed, sick), 2025
4
1.09
[
0.93
; 1.27]
63,503
39,543
not evaluable
Congenital heart defects
Zierler, 1985 Källén, 2003 Rebordosa a, 2008
3
1.05
[
0.97
; 1.15]
1,491
63,333
not evaluable
Hypospadias
Rebordosa a, 2008 Snijder, 2012 Lind, 2013
3
0.94
[
0.80
; 1.10]
1,724
29,826
not evaluable
Cleft palate
Puho, 2007 Rebordosa a, 2008 Feldkamp, 2010
3
1.23
[
0.90
; 1.70]
1,299
28,669
not evaluable
Congenital constriction bands/amniotic band
Werler, 2003 Feldkamp, 2010
2
1.32
[
0.74
; 2.35]
197
9,013
not evaluable
Neural Tube Defects
Pérez-Molina, 2002 Feldkamp, 2010
2
1.32
[
0.49
; 3.54]
817
2,295
not evaluable
Respiratory system anomalies
Rebordosa a, 2008 Broe (Controls unexposed, sick), 2025
2
1.46
[
0.69
; 3.10]
115
35,014
not evaluable
Atresia or stenosis of other parts of small intestine
Werler, 2002 Rebordosa a, 2008
2
0.96
[
0.61
; 1.49]
150
26,801
not evaluable
Cardiac septal defects
Rebordosa a, 2008 Feldkamp, 2010
2
1.04
[
0.94
; 1.15]
2,525
29,390
not evaluable
Cleft lip with or without cleft palate
Puho, 2007 Feldkamp, 2010
2
1.27
[
0.62
; 2.60]
2,484
2,472
not evaluable
Congenital cataract
Rebordosa a, 2008 Feldkamp, 2010
2
0.85
[
0.60
; 1.20]
156
27,853
not evaluable
Congenital glaucoma
Feldkamp, 2010 Cifuentes, 2025
2
1.61
[
0.81
; 3.22]
413
5,925
not evaluable
Craniosynostosis
Rebordosa a, 2008 Feldkamp, 2010
2
1.01
[
0.84
; 1.21]
576
28,620
not evaluable
Eye defects
Rebordosa a, 2008 Cifuentes, 2025
2
1.24
[
0.81
; 1.88]
4,292
31,048
not evaluable
Nervous system anomalies
Winship, 1984 Rebordosa a, 2008
2
0.85
[
0.61
; 1.19]
915
26,465
not evaluable
Oro-facial clefts
Rebordosa a, 2008 Feldkamp, 2010
2
1.03
[
0.92
; 1.16]
1,862
29,136
not evaluable
Spina bifida
Rebordosa a, 2008 Feldkamp, 2010
2
0.83
[
0.42
; 1.63]
473
28,587
not evaluable
Ventricular septal defect
Rebordosa a, 2008 Feldkamp, 2010
2
0.99
[
0.87
; 1.13]
1,166
28,788
not evaluable
Abdominal wall defects
Rebordosa a, 2008
1
0.76
[
0.24
; 2.37]
19
26,424
not evaluable
Ano-rectal atresia and stenosis
Feldkamp, 2010
1
0.85
[
0.68
; 1.07]
365
2,111
not evaluable
Anophthalmos/micropthalmos
Feldkamp, 2010
1
1.00
[
0.66
; 1.52]
101
2,005
not evaluable
Anotia
Feldkamp, 2010
1
1.01
[
0.76
; 1.34]
244
2,054
not evaluable
Arhinencephaly/holoprosencephaly
Feldkamp, 2010
1
1.69
[
0.91
; 3.13]
47
1,983
not evaluable
Atresia of bile ducts
Feldkamp, 2010
1
0.61
[
0.35
; 1.07]
60
1,977
not evaluable
Atrial septal defect
Feldkamp, 2010
1
1.06
[
0.92
; 1.22]
1,199
2,560
not evaluable
Atrioventricular septal defect
Feldkamp, 2010
1
0.90
[
0.60
; 1.36]
104
2,005
not evaluable
Bilateral renal agenesis including Potter syndrome
Feldkamp, 2010
1
1.01
[
0.58
; 1.75]
58
1,985
not evaluable
Bladder exstrophy and/or epispadia
Feldkamp, 2010
1
1.69
[
0.80
; 3.55]
35
1,978
not evaluable
Choanal atresia
Feldkamp, 2010
1
0.79
[
0.44
; 1.41]
53
1,979
not evaluable
Club foot / Talipes equinovarus
Werler, 2014
1
0.98
[
0.79
; 1.22]
570
1,009
not evaluable
Coarctation of aorta
Feldkamp, 2010
1
0.88
[
0.71
; 1.10]
396
2,144
not evaluable
Diaphragmatic hernia
Feldkamp, 2010
1
1.15
[
0.90
; 1.47]
300
2,109
not evaluable
Digestive system anomalies
Rebordosa a, 2008
1
1.01
[
0.72
; 1.41]
188
26,424
not evaluable
Ebstein's anomaly
Feldkamp, 2010
1
1.22
[
0.70
; 2.12]
57
1,987
not evaluable
Encephalocele
Feldkamp, 2010
1
0.98
[
0.61
; 1.58]
79
1,990
not evaluable
Eye, ear, face and neck malformations
Rebordosa a, 2008
1
1.82
[
1.11
; 2.99]
70
26,424
not evaluable
Genital anomalies
Rebordosa a, 2008
1
1.06
[
0.82
; 1.37]
313
26,424
not evaluable
Hip dislocation and/or dysplasia
Rebordosa a, 2008
1
0.97
[
0.81
; 1.16]
645
26,424
not evaluable
Hirschsprung's disease
Rebordosa a, 2008
1
1.00
[
0.53
; 1.88]
48
26,424
not evaluable
Hydrocephaly
Feldkamp, 2010
1
0.92
[
0.67
; 1.26]
181
2,040
not evaluable
Hypoplastic left heart (HLH/HLHS)
Feldkamp, 2010
1
0.95
[
0.71
; 1.28]
206
2,057
not evaluable
Limb defects
Rebordosa a, 2008
1
1.02
[
0.91
; 1.15]
1,495
26,424
not evaluable
Microcephaly / Small head circumference for gestational age
Kerr, 2019
1
0.94
[
0.49
; 1.81]
57
4,625
not evaluable
Minor congenital malformations
Nelson, 1971
1
0.71
[
0.15
; 3.32]
283
11
not evaluable
Oesophageal atresia with or without tracheo-oesophageal fistula
Feldkamp, 2010
1
0.96
[
0.73
; 1.26]
265
2,080
not evaluable
Omphalocele
Feldkamp, 2010
1
0.93
[
0.67
; 1.29]
169
2,031
not evaluable
Pulmonary valve stenosis
Feldkamp, 2010
1
1.11
[
0.91
; 1.36]
508
2,223
not evaluable
Tetralogy of Fallot
Feldkamp, 2010
1
1.05
[
0.84
; 1.31]
395
2,147
not evaluable
Total anomalous pulm venous return
Feldkamp, 2010
1
1.15
[
0.76
; 1.75]
103
2,008
not evaluable
Transposition of the great vessels
Feldkamp, 2010
1
1.10
[
0.87
; 1.39]
342
2,127
not evaluable
Tricuspid atresia and stenosis
Feldkamp, 2010
1
0.89
[
0.51
; 1.55]
59
1,983
not evaluable
Urinary malformations
Rebordosa a, 2008
1
0.90
[
0.69
; 1.18]
300
26,424
not evaluable
Growth parameters and prematurity
Preterm (< 37 weeks)
Thulstrup, 1999 Czeizel, 2005 Rebordosa, 2009 Arneja, 2020 Killion, 2022 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Xu, 2024 Andreasen, 2025
10
1.05
[
0.82
; 1.33]
15,791
27,511
low
Low birth weight (< 2500g)
Thulstrup, 1999 Czeizel, 2005 Rebordosa, 2009 Arneja, 2020 De Castro, 2022 Sznajder, 2022 Zafeiri, 2022 Xu, 2024
8
1.10
[
0.83
; 1.45]
12,145
26,123
serious
Small for gestational age (weight)
Rebordosa, 2009 Arneja, 2020 Killion, 2022 De Castro, 2022 Sznajder, 2022
5
0.96
[
0.91
; 1.01]
6,193
1,518
not evaluable
Macrosomia (> 4000g)
Zafeiri, 2022 Xu, 2024
2
1.24
[
0.71
; 2.16]
16,021
24,597
not evaluable
Very preterm (28 to 32 weeks)
Rebordosa, 2009
1
0.96
[
0.82
; 1.13]
261
-
not evaluable
Maternal consequences
Preeclampsia
Rebordosa, 2010 Killion, 2022
2
1.27
[
0.86
; 1.87]
1,203
19,630
not evaluable
Caesarean
Sznajder, 2022
1
1.29
[
1.09
; 1.54]
712
1,011
not evaluable
Neonatal disorders
Low Apgar score (< 7) (at 5 min)
Sznajder, 2022 Zafeiri, 2022 Xu, 2024
3
1.55
[
0.92
; 2.62]
3,081
25,536
not evaluable
Low Apgar score (< 7) (at 1 min)
Zafeiri, 2022 Xu, 2024
2
1.90
[
0.73
; 4.95]
17,839
24,531
not evaluable
Neonatal medical care
Sznajder, 2022 Zafeiri, 2022
2
1.45
[
1.38
; 1.52]
15,089
21,309
not evaluable
Cerebral palsy
Petersen, 2018
1
1.34
[
1.05
; 1.72]
292
90,830
not evaluable
Jaundice / Icterus
Sznajder, 2022
1
1.18
[
0.97
; 1.43]
540
1,011
not evaluable
Low Apgar score (< 7) (at 10 min)
Xu, 2024
1
3.18
[
1.58
; 6.41]
60
501
not evaluable
Neonatal death (< 28 days of life)
Zafeiri, 2022
1
1.56
[
1.24
; 1.96]
490
23,704
not evaluable
Neonatal intracranial hemorrhage
Rumack, 1981
1
1.29
[
0.48
; 3.49]
41
20
not evaluable
Long term consequences
Childhood asthma
Rebordosa b, 2008 Persky, 2008 Andersen, 2012 Magnus (Controls unexposed, NOS), 2016 Shaheen (Controls unexposed, general pop), 2019 Malaeb, 2021 Liew, 2021
7
1.34
[
1.18
; 1.52]
27,130
15,601
not evaluable
Childhood wheezing
Persky, 2008 Rebordosa b, 2008 Garcia-Marcos, 2009 Perzanowski, 2010 Goksor, 2011 Liew, 2021
6
1.24
[
1.09
; 1.42]
1,782
8,539
not evaluable
Infant allergies
Koniman, 2007 Jedrychowski, 2011 Li, 2021
3
1.18
[
0.88
; 1.58]
2,546
5,331
not evaluable
Leukemia
Ross, 2003 Ognjanovic, 2011
2
1.04
[
0.72
; 1.50]
504
426
not evaluable
Child/Infant weight abnormalities (>= 1 year)
Liew_Girls, 2019 Liew_Boys, 2019
2
1.06
[
0.98
; 1.16]
2,187
13,681
not evaluable
Child/infant diabetes Type 1
Tapia, 2018
1
1.22
[
0.97
; 1.53]
162
-
not evaluable
Child/infant digestive auto-immune diseases (Crohn, Coeliac disease , …)
Marild, 2017
1
1.11
[
0.94
; 1.31]
617
39,117
not evaluable
Intrauterine deaths
Early intrauterine deaths (< 22 weeks) / Spontaneous abortions
Li, 2003 Rebordosa, 2009 Li (Controls unexposed, NOS), 2018
3
1.03
[
0.92
; 1.15]
2,727
563
not evaluable
Late intrauterine deaths (> 22 weeks) / Stillbirths
Pastore, 1999 Rebordosa, 2009 Zafeiri, 2022 Xu, 2024
4
1.21
[
0.84
; 1.73]
1,684
24,699
not evaluable
Neuro-developmental disorders
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk
Liew, 2014 Ystrom or Gustavson (Ystrom - Population-Based), 2017 Tovo-Rodrigues, 2018 Chen, 2019 Sznajder, 2022 Ahlqvist (Population-Based), 2024 Okubo (Controls unexposed, general population), 2025 Pleau, 2025
8
1.16
[
1.09
; 1.24]
162,443
323,950
serious
ADHD (Attention deficit hyperactivity disorder): Diagnosis
Liew, 2014 Ystrom or Gustavson (Ystrom - Population-Based), 2017 Chen, 2019 Ahlqvist (Population-Based), 2024 Okubo (Controls unexposed, general population), 2025 Pleau, 2025
6
1.16
[
1.07
; 1.25]
161,166
321,989
serious
ASD (Autism spectrum disorder): Diagnosis
Liew b, 2016 Ahlqvist (Population-Based), 2024 Okubo (Controls unexposed, general population), 2025
3
1.07
[
1.02
; 1.13]
69,611
264,219
not evaluable
ASD (Autism spectrum disorder): Diagnosis/Risk
Liew b, 2016 Ahlqvist (Population-Based), 2024 Okubo (Controls unexposed, general population), 2025
3
1.07
[
1.02
; 1.13]
69,611
264,219
not evaluable
Language disorders/delay
Liew a, 2016 Bertoldi_Pelotas, 2020 Tovo-Rodrigues, 2020 Tronnes, 2020 Woodbury a, 2024
5
1.00
[
0.99
; 1.01]
1,430
5,316
not evaluable
ADHD (Attention deficit hyperactivity disorder): Risk
Tovo-Rodrigues, 2018 Inoue, 2021 Sznajder, 2022
3
1.15
[
1.06
; 1.24]
3,069
23,631
not evaluable
Cognitive developmental disorders/delay (3-6 years old)
Liew a, 2016 Okubo (Controls unexposed, general population), 2025
2
1.07
[
0.96
; 1.19]
-
43,004
not evaluable
Psychomotor developmental disorders/delay
Vlenterie, 2016 Tovo-Rodrigues, 2020 Bertoldi_Pelotas, 2020
3
1.04
[
0.82
; 1.31]
321
4,100
not evaluable
Cognitive developmental disorders/delay (< 3 years old)
Tovo-Rodrigues, 2020 Bertoldi_Pelotas, 2020
2
0.93
[
0.83
; 1.03]
-
2,470
not evaluable
Cognitive developmental disorders/delay (> 6 years old)
Ahlqvist (Population-Based), 2024
1
1.05
[
1.00
; 1.10]
24,554
185,909
not evaluable
Neuro-developmental disorders (as a whole)
Okubo (Controls unexposed, general population), 2025
1
1.08
[
1.01
; 1.16]
-
42,123
not evaluable
Severe cognitive developmental delay (Mental retardation) (3-6 years old)
Okubo (Controls unexposed, general population), 2025
1
1.03
[
0.91
; 1.17]
-
42,123
not evaluable
Severe cognitive developmental delay (Mental retardation) (> 6 years old)
Ahlqvist (Population-Based), 2024
1
1.05
[
1.00
; 1.10]
24,554
185,909
not evaluable
ASD (Autism spectrum disorder): Risk
Alemany_DNBC, 2021
1
1.28
[
1.10
; 1.49]
729
34,584
not evaluable
Childhood autism (F84.0)
Liew b, 2016
1
1.10
[
0.89
; 1.36]
345
36,187
not evaluable
0.0
10.0
1.0