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Summary
Overall results
Study description
Excluded
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
paused exposure during pregnancy
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
ERROR sometimes
Whatever the period exposition
all type of study
cohort only
case-control only
all studies whatever ROB
low or moderate ROB only
critical ROB only
individual studies
Outcome
TE
95% CI
n cases
n exposed
k
Pub. bias
All congenital malformations (majors, minors, majors and minors, or unspecified)
Einarson (Unexposed control), 2004 Andersen, 2013 Danielsson, 2014 Ozdemirci, 2014 Fejzo (Unexposed control, disease free), 2016 Huybrechts (Unexposed control), 2018 Bérard, 2019 Huybrechts, 2019
8
1.04
[
0.96
; 1.12]
167,592
116,161
not evaluable
Cleft lip with or without cleft palate
Anderka, 2012 Pasternak, 2013 Fejzo (Unexposed control, disease free), 2016 Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018 Parker, BDS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
7
1.03
[
0.88
; 1.21]
4,585
92,238
not evaluable
Congenital heart defects
Andersen, 2013 Danielsson, 2014 Fejzo (Unexposed control, disease free), 2016 Huybrechts (Unexposed control), 2018 Zambelli-Weiner (Unexposed control, sick), 2019 Huybrechts, 2019
6
1.13
[
0.96
; 1.33]
59,616
116,155
not evaluable
Major congenital malformations
Einarson (Unexposed control), 2004 Andersen, 2013 Colvin, 2013 Danielsson, 2014 Huybrechts (Unexposed control), 2018 Bérard, 2019 Huybrechts, 2019
7
1.02
[
0.99
; 1.05]
150,947
115,320
not evaluable
Ventricular septal defect
Pasternak, 2013 Fejzo (Unexposed control, disease free), 2016 Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018 Parker, BDS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019 Lemon, 2019
7
1.13
[
0.99
; 1.27]
19,110
96,086
not evaluable
Cleft palate
Anderka, 2012 Pasternak, 2013 Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018 Parker, BDS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
6
1.26
[
0.87
; 1.82]
3,363
91,261
not evaluable
Atrial septal defect
Pasternak, 2013 Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018 Parker, BDS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
5
1.05
[
0.79
; 1.39]
5,715
91,265
not evaluable
Hypospadias
Anderka, 2012 Pasternak, 2013 Lind (Controls unexposed, NOS), 2013 Parker, NBDPS study, 2018 Parker, BDS study, 2018
5
0.90
[
0.70
; 1.15]
3,323
1,874
not evaluable
Oro-facial clefts
Pasternak, 2013 Huybrechts (Unexposed control), 2018 Zambelli-Weiner (Unexposed control, sick), 2019 Huybrechts, 2019
4
1.20
[
1.02
; 1.40]
3,506
113,549
not evaluable
Atrioventricular septal defect
Pasternak, 2013 Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
4
1.38
[
0.65
; 2.93]
6,190
90,765
not evaluable
Club foot / Talipes equinovarus
Pasternak, 2013 Werler, 2014 Fejzo (Unexposed control, disease free), 2016 Parker, BDS study, 2018
4
1.09
[
0.83
; 1.44]
1,061
2,714
not evaluable
Limb defects
Pasternak, 2013 Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018 Parker, BDS study, 2018
4
1.02
[
0.92
; 1.11]
8,425
90,330
not evaluable
Ano-rectal atresia and stenosis
Pasternak, 2013 Parker, NBDPS study, 2018 Parker, BDS study, 2018
3
0.79
[
0.49
; 1.27]
671
1,881
not evaluable
Atresia or stenosis of other parts of small intestine
Pasternak, 2013 Parker, NBDPS study, 2018 Parker, BDS study, 2018
3
0.97
[
0.61
; 1.53]
394
1,880
not evaluable
Coarctation of aorta
Pasternak, 2013 Parker, NBDPS study, 2018 Parker, BDS study, 2018
3
0.95
[
0.69
; 1.29]
844
1,903
not evaluable
Craniosynostosis
Pasternak, 2013 Parker, NBDPS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
3
1.13
[
0.95
; 1.35]
12,765
2,512
not evaluable
Diaphragmatic hernia
Pasternak, 2013 Parker, NBDPS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
3
1.70
[
1.17
; 2.48]
875
2,394
not evaluable
Gastroschisis
Pasternak, 2013 Parker, NBDPS study, 2018 Parker, BDS study, 2018
3
0.89
[
0.61
; 1.29]
959
1,894
not evaluable
Hypoplastic left heart
Parker, NBDPS study, 2018 Parker, BDS study, 2018 Zambelli-Weiner (Unexposed control, NOS), 2019
3
1.49
[
1.03
; 2.17]
838
1,539
not evaluable
Pulmonary valve stenosis
Pasternak, 2013 Parker, NBDPS study, 2018 Parker, BDS study, 2018
3
1.08
[
0.79
; 1.48]
1,025
1,913
not evaluable
Severe congenital heart defect
Huybrechts (Unexposed control), 2018 Parker, BDS study, 2018
2
0.76
[
0.63
; 0.93]
1,880
88,851
not evaluable
Single ventricle
Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018
2
0.90
[
0.34
; 2.37]
424
88,706
not evaluable
Total anomalous pulm venous return
Parker, NBDPS study, 2018 Huybrechts (Unexposed control), 2018
2
0.84
[
0.55
; 1.30]
502
88,705
not evaluable
Abdominal wall defects
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
0.98
[
0.90
; 1.07]
8,816
89,679
not evaluable
Bilateral renal agenesis including Potter syndrome
Pasternak, 2013 Parker, BDS study, 2018
2
1.85
[
1.13
; 3.02]
161
1,630
not evaluable
Cardiac septal defects
Danielsson, 2014 Zambelli-Weiner (Unexposed control, NOS), 2019
2
1.57
[
1.17
; 2.12]
39,475
2,528
not evaluable
Congenital cataract
Pasternak, 2013 Parker, NBDPS study, 2018
2
0.94
[
0.46
; 1.91]
211
1,494
not evaluable
Digestive system anomalies
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
0.93
[
0.85
; 1.02]
9,598
89,700
not evaluable
Eye defects
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
0.95
[
0.69
; 1.30]
772
89,700
not evaluable
Genital anomalies
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
1.06
[
0.97
; 1.17]
7,100
89,679
not evaluable
Limb reduction defects
Pasternak, 2013 Zambelli-Weiner (Unexposed control, NOS), 2019
2
1.01
[
0.39
; 2.58]
563
2,115
not evaluable
Nervous system anomalies
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
0.94
[
0.81
; 1.09]
3,496
89,679
not evaluable
Oesophageal atresia with or without tracheo-oesophageal fistula
Pasternak, 2013 Parker, NBDPS study, 2018
2
0.71
[
0.40
; 1.28]
364
1,496
not evaluable
Patent ductus arterious
Huybrechts (Unexposed control), 2018
1
0.90
[
0.73
; 1.11]
1,675
88,446
not evaluable
Respiratory system anomalies
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
1.13
[
1.01
; 1.27]
3,951
89,679
not evaluable
Spina bifida
Parker, NBDPS study, 2018 Parker, BDS study, 2018
2
1.24
[
0.83
; 1.83]
461
620
not evaluable
Transposition of the great vessels
Parker, NBDPS study, 2018 Parker, BDS study, 2018
2
0.80
[
0.52
; 1.23]
584
649
not evaluable
Urinary malformations
Pasternak, 2013 Huybrechts (Unexposed control), 2018
2
1.24
[
0.76
; 2.01]
176
89,679
not evaluable
Anophthalmos/micropthalmos
Parker, NBDPS study, 2018
1
0.90
[
0.31
; 2.65]
132
257
not evaluable
Anotia
Parker, NBDPS study, 2018
1
1.10
[
0.59
; 2.06]
354
263
not evaluable
Aortic valve atresia/stenosis
Parker, NBDPS study, 2018
1
0.50
[
0.20
; 1.22]
272
260
not evaluable
Atresia of bile ducts
Parker, NBDPS study, 2018
1
1.30
[
0.51
; 3.29]
101
258
not evaluable
Choanal atresia
Pasternak, 2013
1
1.33
[
0.05
; 32.76]
1
1,233
not evaluable
Congenital constriction bands/amniotic band
Parker, NBDPS study, 2018
1
1.30
[
0.51
; 3.29]
155
258
not evaluable
Congenital glaucoma
Pasternak, 2013
1
4.00
[
0.25
; 64.04]
2
1,233
not evaluable
Congenital hydronephrosis
Pasternak, 2013
1
0.80
[
0.17
; 3.65]
12
1,233
not evaluable
Congenital skin disorders
Pasternak, 2013
1
0.57
[
0.03
; 11.07]
3
1,233
not evaluable
Ear malformations
Huybrechts (Unexposed control), 2018
1
1.67
[
1.17
; 2.38]
450
88,446
not evaluable
Ear, face and neck anomalies
Pasternak, 2013
1
4.00
[
0.25
; 64.04]
2
1,233
not evaluable
Ebstein's anomaly
Parker, NBDPS study, 2018
1
1.10
[
0.39
; 3.11]
108
257
not evaluable
0.0
100.0
1.0