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- medecines during pregnancy KB
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Valproate (All indications)
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
Whatever the period exposition
individual studies
Outcome
TE
95% CI
n cases
n exposed
k
Pub. bias
Congenital malformations
All congenital malformations (majors, minors, majors and minors, or unspecified)
Jäger-Roman (Valproate), 1986 Robert (Valproate), 1986 D'Souza (Valproate) (Controls unexposed, sick), 1991 Kaneko (Valproate), 1999 Samrén (Valproate), 1999 Canger (Valproate), 1999 Hvas (Valproate) (Controls unexposed, sick), 2000 Dean (Valproate), 2002 Kaaja (Valproate), 2003 Endo (Valproate) (Controls unexposed, sick), 2004 Artama (Valproate), 2005 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Diav-Citrin (Valproate) (Mixed indications), 2008 Mawer (Valproate) (Controls unexposed, sick), 2010 Bànhidy (Valproate), 2011 Charlton (Valproate) (Controls unexposed, sick), 2011 Arteaga-Vázquez (Valproate), 2012 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Cassina (Valproate) (Controls unexposed, disease free) (Mixed indications), 2013 Veiby (Valproate) (Controls unexposed, sick) (Mixed indications), 2014 Campbell (Valproate) (Controls unexposed, sick), 2014 Vanya (Valproate) (Controls unexposed, sick), 2015 Petersen (Valproate) (Controls unexposed, sick), 2017 Tomson (Valproate), 2018 Huber-Mollema (Valproate), 2019 Vajda (Valproate) (Controls unexposed, sick), 2019 Putignano (Valproate), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020 Thomas (Valproate) (Controls unexposed, sick), 2021 Hosny (Valproate) (Controls unexposed, sick), 2021 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
33
3.16
[
2.64
; 3.78]
198,716
8,172
critical
Major congenital malformations
Robert (Valproate), 1986 Jäger-Roman (Valproate), 1986 Samrén (Valproate), 1999 Canger (Valproate), 1999 Hvas (Valproate) (Controls unexposed, sick), 2000 Dean (Valproate), 2002 Kaaja (Valproate), 2003 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Diav-Citrin (Valproate) (Mixed indications), 2008 Mawer (Valproate) (Controls unexposed, sick), 2010 Charlton (Valproate) (Controls unexposed, sick), 2011 Bànhidy (Valproate), 2011 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Cassina (Valproate) (Controls unexposed, disease free) (Mixed indications), 2013 Veiby (Valproate) (Controls unexposed, sick) (Mixed indications), 2014 Campbell (Valproate) (Controls unexposed, sick), 2014 Vanya (Valproate) (Controls unexposed, sick), 2015 Petersen (Valproate) (Controls unexposed, sick), 2017 Tomson (Valproate), 2018 Vajda (Valproate) (Controls unexposed, sick), 2019 Huber-Mollema (Valproate), 2019 Thomas (Valproate) (Controls unexposed, sick), 2021 Hosny (Valproate) (Controls unexposed, sick), 2021 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
25
3.01
[
2.46
; 3.68]
198,528
7,694
critical
Congenital heart defects
D'Souza (Valproate) (Controls unexposed, sick), 1991 Canger (Valproate), 1999 Artama (Valproate), 2005 Diav-Citrin (Valproate) (Mixed indications), 2008 Mawer (Valproate) (Controls unexposed, sick), 2010 Bànhidy (Valproate), 2011 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Vajda (Valproate) (Controls unexposed, sick), 2013 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Tomson (Valproate), 2018 Thomas (Valproate) (Controls unexposed, sick), 2021 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
15
2.74
[
2.19
; 3.44]
18,389
7,248
low
Hypospadias
D'Souza (Valproate) (Controls unexposed, sick), 1991 Diav-Citrin (Valproate) (Mixed indications), 2008 Bànhidy (Valproate), 2011 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Valproate) (Controls unexposed, disease free) (Mixed indications), 2014 Tomson (Valproate), 2018 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
10
5.88
[
4.60
; 7.51]
9,567
6,978
low
Limb defects
Artama (Valproate), 2005 Mawer (Valproate) (Controls unexposed, sick), 2010 Vajda (Valproate) (Controls unexposed, sick), 2013 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Thomas (Valproate) (Controls unexposed, sick), 2021
7
2.85
[
1.79
; 4.55]
1,334
2,695
not evaluable
Neural Tube Defects
Canger (Valproate), 1999 Mawer (Valproate) (Controls unexposed, sick), 2010 Bànhidy (Valproate), 2011 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Vajda (Valproate) (Controls unexposed, sick), 2013 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2018
7
9.34
[
4.08
; 21.40]
52
3,298
not evaluable
Spina bifida
Czeizel (Valproate), 1992 Artama (Valproate), 2005 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Charlton (Valproate) (Controls unexposed, sick), 2011 Veiby (Valproate) (Controls unexposed, sick) (Mixed indications), 2014 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
6
13.80
[
7.20
; 26.46]
640
1,764
not evaluable
Oro-facial clefts
Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2018 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
7
3.67
[
2.51
; 5.38]
5,618
6,898
not evaluable
Microcephaly / Small head circumference for gestational age
Dravet (Valproate), 1992 Battino (Valproate), 1999 Díaz-Romero (Valproate), 1999 Kini (Valproate) (Controls unexposed, sick), 2006 Pennell (Valproate), 2012 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
6
1.36
[
0.67
; 2.78]
472
1,112
not evaluable
Polydactyly
D'Souza (Valproate) (Controls unexposed, sick), 1991 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Bànhidy (Valproate), 2011 Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Tomson (Valproate), 2018
5
2.41
[
0.43
; 13.52]
3,095
2,112
not evaluable
Nervous system anomalies
Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015 Thomas (Valproate) (Controls unexposed, sick), 2021 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
4
3.08
[
1.88
; 5.03]
374
2,919
not evaluable
Club foot / Talipes equinovarus
Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023
3
4.97
[
3.12
; 7.91]
3,810
3,641
not evaluable
Urinary malformations
Artama (Valproate), 2005 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Tomson (Valproate), 2018 Thomas (Valproate) (Controls unexposed, sick), 2021
4
1.18
[
0.56
; 2.49]
29
2,318
not evaluable
Cardiac septal defects
Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013 Veiby (Valproate) (Controls unexposed, disease free) (Mixed indications), 2014
2
2.67
[
1.74
; 4.10]
16,578
1,030
not evaluable
Cleft lip with or without cleft palate
Artama (Valproate), 2005 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
3
5.08
[
1.87
; 13.82]
1,647
1,204
not evaluable
Craniosynostosis
D'Souza (Valproate) (Controls unexposed, sick), 1991 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
2
6.12
[
1.26
; 29.85]
768
914
not evaluable
Digestive system anomalies
Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Thomas (Valproate) (Controls unexposed, sick), 2021
3
1.46
[
0.65
; 3.30]
23
1,894
not evaluable
Genital anomalies
Artama (Valproate), 2005 Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Ban (Valproate) (Mixed indications) (Controls unexposed NOS), 2015
3
3.25
[
1.54
; 6.89]
1,045
810
not evaluable
Cleft palate
Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
2
4.85
[
1.37
; 17.12]
1,181
941
not evaluable
Minor congenital malformations
Robert (Valproate), 1986 Battino (Valproate), 1992 Dean (Valproate), 2002
3
5.11
[
2.13
; 12.25]
43
83
not evaluable
Ano-rectal atresia and stenosis
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
11.70
[
3.09
; 44.30]
547
913
not evaluable
Atrial septal defect
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
9.00
[
5.40
; 15.00]
3,283
913
not evaluable
Atrioventricular septal defect
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
1.94
[
0.12
; 31.09]
529
913
not evaluable
Bilateral renal agenesis including Potter syndrome
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
13.61
[
0.84
; 219.81]
75
913
not evaluable
Bladder exstrophy and/or epispadia
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
12.46
[
0.77
; 201.01]
82
913
not evaluable
Coarctation of aorta
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
1.32
[
0.08
; 21.11]
779
913
not evaluable
Diaphragmatic hernia
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
2.71
[
0.17
; 43.52]
378
913
not evaluable
Down syndrom / Trisomy 21
D'Souza (Valproate) (Controls unexposed, sick), 1991
1
15.00
[
0.12
; 1923.88]
-
1
not evaluable
Ebstein's anomaly
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
20.35
[
1.25
; 330.13]
50
913
not evaluable
Eye defects
Dean (Valproate), 2002 Artama (Valproate), 2005
2
0.45
[
0.12
; 1.72]
10
309
not evaluable
Gastroschisis
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
4.22
[
0.26
; 67.72]
243
913
not evaluable
Hip dislocation and/or dysplasia
D'Souza (Valproate) (Controls unexposed, sick), 1991
1
15.00
[
0.12
; 1923.88]
-
1
not evaluable
Hypoplastic left heart (HLH/HLHS)
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
19.60
[
3.59
; 107.13]
218
913
not evaluable
Hypoplastic right heart (HRH/HRHS)
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
15.46
[
0.96
; 249.87]
66
913
not evaluable
Oesophageal atresia with or without tracheo-oesophageal fistula
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
2.62
[
0.16
; 41.96]
392
913
not evaluable
Omphalocele
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
3.86
[
0.24
; 61.86]
266
913
not evaluable
Pulmonary valve atresia
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
27.80
[
4.99
; 154.94]
154
913
not evaluable
Tetralogy of Fallot
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
7.20
[
1.33
; 38.92]
586
913
not evaluable
Valproate syndrome
0
-
-
-
-
-
Ventricular septal defect
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
4.00
[
2.08
; 7.71]
4,652
913
not evaluable
Chromosomal abnormalities
Artama (Valproate), 2005
1
10.77
[
0.44
; 265.09]
1
263
not evaluable
Ear, face and neck anomalies
Artama (Valproate), 2005
1
0.71
[
0.03
; 14.91]
2
263
not evaluable
Eye, ear, face and neck malformations
Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014
1
2.51
[
0.16
; 40.18]
2
333
not evaluable
Respiratory system anomalies
Veiby (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014
1
0.50
[
0.02
; 10.43]
2
333
not evaluable
Growth parameters and prematurity
Preterm (< 37 weeks)
Jäger-Roman (Valproate), 1986 Endo (Valproate) (Controls unexposed, sick), 2004 McVearry (Valproate), 2009 Nadebaum (Valproate), 2011 Cummings (Valproate) (Controls unexposed, disease free), 2011 Pennell (Valproate), 2012 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Artama (Valproate) (Controls unexposed, sick), 2013 Kilic (Valproate) (Controls unexposed, sick) (Mixed indications), 2014 Arkilo (Valproate), 2015 Bank (Valproate) (Mixed indications), 2017 Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Putignano (Valproate), 2019 Coste (Valproate) (Controls unexposed, NOS), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020
15
1.08
[
0.99
; 1.17]
252,978
4,796
low
Small for gestational age (weight)
Endo (Valproate) (Controls unexposed, sick), 2004 Burja (Valproate) (Controls unexposed, sick), 2006 Pennell (Valproate), 2012 Artama (Valproate) (Controls unexposed, sick), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Kilic (Valproate) (Controls unexposed, sick) (Mixed indications), 2014 Bank (Valproate) (Mixed indications), 2017 Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Putignano (Valproate), 2019 Coste (Valproate) (Controls unexposed, NOS), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Dreier (Valproate), 2021
12
1.32
[
1.00
; 1.74]
210,116
6,632
low
Low birth weight (< 2500g)
Kini (Valproate) (Controls unexposed, sick), 2006 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Artama (Valproate) (Controls unexposed, sick), 2013 Kilic (Valproate) (Controls unexposed, sick) (Mixed indications), 2014 Wen (Valproate) (Mixed indications), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020
6
1.49
[
1.23
; 1.82]
94,912
2,363
not evaluable
Large for gestational age (weight)
Artama (Valproate) (Controls unexposed, sick), 2013 Putignano (Valproate), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020
3
1.21
[
0.74
; 1.98]
158
845
not evaluable
Macrosomia (> 4000g)
Endo (Valproate) (Controls unexposed, sick), 2004 Kini (Valproate) (Controls unexposed, sick), 2006 Coste (Valproate) (Controls unexposed, NOS), 2020
3
0.91
[
0.55
; 1.51]
577,407
1,059
not evaluable
Very preterm (28 to 32 weeks)
Coste (Valproate) (Controls unexposed, NOS), 2020
1
1.21
[
0.54
; 2.70]
8,590
991
not evaluable
Extremely preterm (< 28 weeks)
Coste (Valproate) (Controls unexposed, NOS), 2020
1
0.85
[
0.12
; 6.01]
2,042
991
not evaluable
Large head circumference for gestational age
Díaz-Romero (Valproate), 1999
1
0.79
[
0.01
; 44.65]
-
10
not evaluable
Very low birth weight (< 1500g)
Wen (Valproate) (Mixed indications), 2017
1
0.63
[
0.09
; 4.51]
309
226
not evaluable
Maternal consequences
Caesarean
Endo (Valproate) (Controls unexposed, sick), 2004 Borthen (Valproate) (Controls unexposed, sick), 2010 Artama (Valproate) (Controls unexposed, sick), 2013
3
0.93
[
0.76
; 1.14]
831
926
not evaluable
Preeclampsia
Borthen (Valproate) (Controls unexposed, sick), 2011 Pennell (Valproate), 2012 Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020
4
0.95
[
0.78
; 1.15]
53,760
2,489
not evaluable
Assisted deliveries (forceps, vacuum, ...)
Endo (Valproate) (Controls unexposed, sick), 2004 Borthen (Valproate) (Controls unexposed, sick), 2010
2
1.18
[
0.73
; 1.90]
177
220
not evaluable
Gestational diabetes
McVearry (Valproate), 2009 Pennell (Valproate), 2012 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Aydin (Valproate) (Controls unexposed, sick), 2020
4
1.60
[
0.23
; 10.91]
14
110
not evaluable
Postpartum hemorrhage
Borthen (Valproate) (Controls unexposed, sick), 2010
1
1.44
[
1.01
; 2.06]
319
215
not evaluable
Abruptio placentae (retroplacental hematoma)
Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019
1
1.25
[
0.94
; 1.66]
20,322
2,398
not evaluable
Amniotic fluid problems (polyhydramnios and/or oligohydramnios)
Aydin (Valproate) (Controls unexposed, sick), 2020
1
2.05
[
0.04
; 110.56]
-
11
not evaluable
Maternal consequences (as a whole)
Wen (Valproate) (Mixed indications), 2017 Alsfouk (Valproate), 2022
2
1.35
[
1.03
; 1.77]
12,260
238
not evaluable
Polyhydramnios
Endo (Valproate) (Controls unexposed, sick), 2004
1
0.11
[
0.00
; 14.76]
-
5
not evaluable
Neonatal disorders
Low Apgar score (< 7) (at 5 min)
Borthen (Valproate) (Controls unexposed, sick), 2010 Pennell (Valproate), 2012 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Artama (Valproate) (Controls unexposed, sick), 2013 Christensen (Valproate) (Controls unexposed, sick) (Mixed indications), 2015 Bank (Valproate) (Mixed indications), 2017 Putignano (Valproate), 2019
7
1.76
[
1.06
; 2.91]
137
1,026
not evaluable
Neonatal medical care
D'Souza (Valproate) (Controls unexposed, sick), 1991 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 Artama (Valproate) (Controls unexposed, sick), 2013 Bank (Valproate) (Mixed indications), 2017 Putignano (Valproate), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020
6
1.98
[
1.52
; 2.59]
2,098
777
not evaluable
Low Apgar score (< 7) (at 1 min)
Endo (Valproate) (Controls unexposed, sick), 2004 Pennell (Valproate), 2012 Artama (Valproate) (Controls unexposed, sick), 2013 Bank (Valproate) (Mixed indications), 2017
4
2.39
[
0.84
; 6.81]
134
673
not evaluable
Neonatal disorders (as a whole)
D'Souza (Valproate) (Controls unexposed, sick), 1991 Wen (Valproate) (Mixed indications), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020
3
1.05
[
0.76
; 1.44]
225,753
1,218
not evaluable
Withdrawal syndrome / Neonatal abstinence syndrome / Poor neonatal adaptation
Burja (Valproate) (Controls unexposed, sick), 2006
1
Out of scale
189.00
[
2.70
; 13229.55]
1
2
not evaluable
Feeding difficulty
D'Souza (Valproate) (Controls unexposed, sick), 1991 Burja (Valproate) (Controls unexposed, sick), 2006
2
24.38
[
1.49
; 397.73]
2
3
not evaluable
Fetal distress
McVearry (Valproate), 2009
1
0.09
[
0.00
; 1.83]
4
16
not evaluable
Neonatal intracranial hemorrhage
D'Souza (Valproate) (Controls unexposed, sick), 1991 Burja (Valproate) (Controls unexposed, sick), 2006
2
15.00
[
1.09
; 206.94]
3
3
not evaluable
Jaundice
D'Souza (Valproate) (Controls unexposed, sick), 1991
1
4.33
[
0.06
; 320.42]
1
1
not evaluable
Neonatal hypotonia
D'Souza (Valproate) (Controls unexposed, sick), 1991
1
15.00
[
0.12
; 1923.88]
-
1
not evaluable
Neonatal infections
D'Souza (Valproate) (Controls unexposed, sick), 1991
1
15.00
[
0.12
; 1923.88]
-
1
not evaluable
Neonatal tachypnea
D'Souza (Valproate) (Controls unexposed, sick), 1991
1
15.00
[
0.12
; 1923.88]
-
1
not evaluable
Very low Apgar score (< 5) (at 1 min)
0
-
-
-
-
-
Long term consequences
Behavioral disorders
Veiby (Valproate) (Controls unexposed, sick) b, 2013 Cohen (Valproate), 2013 Bromley (Valproate), 2016 Huber-Mollema (Valproate), 2019 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023
5
0.93
[
0.65
; 1.34]
151
2,088
not evaluable
Emotional disorders
Cohen (Valproate), 2013 Bromley (Valproate), 2016 Huber-Mollema (Valproate), 2019 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023
4
0.97
[
0.77
; 1.22]
591
2,069
not evaluable
Child/Infant death (> 28 days of life)
Artama (Valproate) (Controls unexposed, sick), 2013 Coste (Valproate) (Controls unexposed, NOS), 2020
2
3.01
[
1.62
; 5.60]
4,714
1,694
not evaluable
Child/Infant growth abnormalities (> 1 year)
Pennell (Valproate), 2012
1
0.24
[
0.03
; 2.07]
7
44
not evaluable
Child/Infant head circumference abnormalities (> 1 year)
Pennell (Valproate), 2012
1
1.39
[
0.03
; 71.26]
-
42
not evaluable
Child/Infant lenght abnormalities (> 1 year)
Kini (Valproate) (Controls unexposed, sick), 2006
1
2.55
[
0.69
; 9.43]
10
63
not evaluable
Child/Infant weight abnormalities (> 1 year)
Kini (Valproate) (Controls unexposed, sick), 2006
1
1.16
[
0.35
; 3.82]
12
63
not evaluable
Intrauterine deaths
Intrauterine deaths (as a whole or unspecified)
Meador (Valproate), 2006 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2015 Arkilo (Valproate), 2015 Miškov (Valproate) (Controls unexposed, sick), 2016 Trivedi (Valproate) (Controls unexposed, sick), 2018 Vajda (Valproate) (Controls unexposed, sick), 2018
7
1.46
[
1.01
; 2.11]
468
3,144
not evaluable
Early intrauterine death (< 22 weeks)
Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Babic (Valproate), 2014 Tomson (Valproate), 2015 Arkilo (Valproate), 2015 Miškov (Valproate) (Controls unexposed, sick), 2016
5
1.04
[
0.84
; 1.29]
366
2,475
not evaluable
Late intrauterine deaths (> 22 weeks)
Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2015 Arkilo (Valproate), 2015 AlSheikh (Valproate) (Controls unexposed, sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020
5
1.83
[
1.01
; 3.31]
42
2,475
not evaluable
Elective/induced termination of pregnancy
Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Miškov (Valproate) (Controls unexposed, sick), 2016 Hosny (Valproate) (Controls unexposed, sick), 2021
3
1.83
[
0.80
; 4.17]
21
1,304
not evaluable
Perinatal death
Canger (Valproate), 1999 Artama (Valproate) (Controls unexposed, sick), 2013 Tomson (Valproate), 2015
3
2.16
[
0.95
; 4.89]
27
1,833
not evaluable
Therapeutic terminations of pregnancy
Miškov (Valproate) (Controls unexposed, sick), 2016
1
0.64
[
0.01
; 40.08]
-
6
not evaluable
Ectopic pregnancy
Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014
1
1.70
[
0.03
; 85.94]
-
1,290
not evaluable
Neuro-developmental disorders
Language disorders/delay
Gaily (Valproate) (Controls unexposed, sick), 2004 Adab (Valproate), 2004 Eriksson (Valproate), 2005 Shallcross (Valproate), 2011 Nadebaum (Valproate), 2011 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Meador (Valproate), 2013 Baker (Valproate) (Controls unexposed, sick), 2015 Deshmukh (Valproate), 2016 Videman (Valproate) (Controls unexposed, disease free), 2016 Bromley (Valproate), 2016 Kasradze (Valproate) (Controls unexposed, disease free), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020 Husebye (Valproate) (Controls unexposed, sick), 2020 Thomas (Valproate), 2022
15
2.87
[
2.05
; 4.02]
72,249
1,423
critical
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk
Adab (Valproate), 2004 Viinikainen (Valproate) b, 2006 Cohen (Valproate), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Bromley (Valproate) (Controls unexposed, sick), 2013 Bromley (Valproate), 2016 Huber-Mollema (Valproate), 2019 Richards (Valproate) (Controls unexposed, NOS) (Indications NOS), 2019 Wiggs (Valproate), 2020 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023
11
1.52
[
1.28
; 1.81]
12,513
2,387
low
Cognitive developmental disorders/delay (> 6 years old)
Gaily (Valproate) (Controls unexposed, sick), 2004 Adab (Valproate), 2004 Vinten (Valproate), 2005 Viinikainen (Valproate) b, 2006 Titze (Valproate) (Controls unexposed, sick), 2008 Nadebaum (Valproate), 2011 Meador (Valproate), 2013 Baker (Valproate) (Controls unexposed, sick), 2015 Bromley (Valproate), 2016 Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022 Thomas (Valproate), 2022
11
2.99
[
2.00
; 4.48]
246
2,735
low
Neuro-developmental disorders (as a whole)
Katz (Valproate), 2001 Adab (Valproate), 2004 Viinikainen (Valproate) b, 2006 Dean (Valproate) (Controls unexposed, sick), 2007 Bromley (Valproate) (Controls unexposed, sick), 2013 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Arkilo (Valproate), 2015 Charlton (Valproate), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020 Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022
10
4.09
[
3.54
; 4.73]
10,826
3,740
low
ASD (Autism spectrum disorder): Diagnosis/Risk
Adab (Valproate), 2004 Bromley (Valproate) (Controls unexposed, sick), 2013 Wood (Valproate), 2015 Bjørk (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Bjørk (Valproate) (Controls unexposed, sick), 2018 Huber-Mollema (Valproate), 2019 Wiggs (Valproate), 2020 Coste (Valproate) (Controls unexposed, NOS), 2020 Bjørk (Valproate) (Controls unexposed NOS) (Mixed indications), 2022 Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022
10
2.86
[
2.23
; 3.67]
43,224
6,052
low
Psychomotor developmental disorders/delay
Koch (Valproate), 1996 Adab (Valproate), 2004 Viinikainen (Valproate) b, 2006 Thomas b (Valproate), 2008 Shallcross (Valproate), 2011 Cohen (Valproate), 2011 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Bromley (Valproate) (Controls unexposed, sick), 2013 Deshmukh (Valproate), 2016 Videman (Valproate) (Controls unexposed, disease free), 2016
10
3.03
[
1.99
; 4.64]
82
373
low
ASD (Autism spectrum disorder): Diagnosis
Adab (Valproate), 2004 Bromley (Valproate) (Controls unexposed, sick), 2013 Wood (Valproate), 2015 Huber-Mollema (Valproate), 2019 Wiggs (Valproate), 2020 Coste (Valproate) (Controls unexposed, NOS), 2020 Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022
7
2.91
[
2.40
; 3.53]
4,659
3,577
not evaluable
Cognitive developmental disorders/delay (3-6 years old)
Gaily (Valproate) (Controls unexposed, sick), 2004 Cummings (Valproate) (Controls unexposed, disease free), 2011 Meador (Valproate), 2013 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Deshmukh (Valproate), 2016 Kasradze (Valproate) (Controls unexposed, disease free), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020
7
5.06
[
2.73
; 9.37]
3,466
1,199
not evaluable
ADHD (Attention deficit hyperactivity disorder): Diagnosis
Adab (Valproate), 2004 Bromley (Valproate) (Controls unexposed, sick), 2013 Cohen (Valproate), 2013 Huber-Mollema (Valproate), 2019 Wiggs (Valproate), 2020 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023
6
1.54
[
1.27
; 1.86]
653
2,119
not evaluable
ADHD (Attention deficit hyperactivity disorder): Risk
Viinikainen (Valproate) b, 2006 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 Cohen (Valproate), 2013 Bromley (Valproate), 2016 Richards (Valproate) (Controls unexposed, NOS) (Indications NOS), 2019 Huber-Mollema (Valproate), 2019
7
1.51
[
0.99
; 2.32]
11,883
339
not evaluable
Severe cognitive developmental delay (Mental retardation) (> 6 years old)
Gaily (Valproate) (Controls unexposed, disease free), 2004 Vinten (Valproate), 2005 Viinikainen (Valproate) b, 2006 Titze (Valproate) (Controls unexposed, sick), 2008 Meador (Valproate), 2013 Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022
6
4.15
[
3.12
; 5.51]
227
2,540
not evaluable
Cognitive developmental disorders/delay (< 3 years old)
Thomas b (Valproate), 2008 Bromley (Valproate) (Controls unexposed, sick), 2010 Shallcross (Valproate), 2011 Meador (Valproate), 2013 Videman (Valproate) (Controls unexposed, disease free), 2016
5
4.09
[
1.87
; 8.96]
103
190
not evaluable
Severe cognitive developmental delay (Mental retardation) (3-6 years old)
Gaily (Valproate) (Controls unexposed, sick), 2004 Cummings (Valproate) (Controls unexposed, disease free), 2011 Meador (Valproate), 2013 Coste (Valproate) (Controls unexposed, NOS), 2020
4
5.02
[
3.12
; 8.08]
3,426
1,101
not evaluable
ASD (Autism spectrum disorder): Risk
Wood (Valproate), 2015 Bjørk (Valproate) (Controls unexposed, sick), 2018 Huber-Mollema (Valproate), 2019
3
1.28
[
0.48
; 3.42]
37
79
not evaluable
Childhood autism (F84.0)
Christensen (Valproate) (Controls unexposed NOS) (Mixed indications), 2013
1
4.90
[
2.32
; 10.37]
2,065
388
not evaluable
Learning disorders
Ren (Valproate) (Mixed indications), 2023
1
1.27
[
1.00
; 1.61]
-
232
not evaluable
Severe cognitive developmental delay (Mental retardation) (< 3 years old)
Meador (Valproate), 2013
1
3.29
[
1.00
; 10.85]
13
29
not evaluable
0.0
100.0
1.0