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Valproate (Paternal exposure)
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
All congenital malformations (majors, minors, majors and minors, or unspecified)
Tomson, 2020 Christensen (Controls unexposed, sick), 2024 Colas_Norway, 2025
3
0.83
[
0.64
; 1.06]
713
1,646
not evaluable
Major congenital malformations
Tomson, 2020 Christensen (Controls unexposed, sick), 2024
2
0.84
[
0.64
; 1.10]
659
1,510
not evaluable
Cardiac septal defects
Christensen (Controls unexposed, general pop), 2024
1
0.53
[
0.23
; 1.21]
-
1,336
not evaluable
Neuro-developmental disorders
ASD (Autism spectrum disorder): Diagnosis
Christensen (Controls unexposed, sick), 2024 Botton, 2025 Meng_Taiwan (Controls unexposed, sick), 2026 Razaz_Sweden, 2026 Meng_Norway (Controls unexposed, sick), 2026
5
1.10
[
0.89
; 1.35]
12,140
6,883
not evaluable
ASD (Autism spectrum disorder): Diagnosis/Risk
Christensen (Controls unexposed, sick), 2024 Botton, 2025 Meng_Taiwan (Controls unexposed, sick), 2026 Razaz_Sweden, 2026 Meng_Norway (Controls unexposed, sick), 2026
5
1.10
[
0.89
; 1.35]
12,140
6,883
not evaluable
Neuro-developmental disorders (as a whole)
Christensen (Controls unexposed, sick), 2024 Botton, 2025 Razaz_Sweden, 2026 Razaz_Norway, 2026
4
1.11
[
0.99
; 1.25]
1,771
6,496
not evaluable
ADHD (Attention deficit hyperactivity disorder): Diagnosis
Christensen (Controls exposed to LTG/LEV), 2024 Botton, 2025 Meng_Taiwan (Controls unexposed, sick), 2026 Razaz_Sweden, 2026 Meng_Norway (Controls unexposed, sick), 2026
5
1.02
[
0.87
; 1.20]
43,031
6,792
not evaluable
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk
Christensen (Controls exposed to LTG/LEV), 2024 Botton, 2025 Meng_Taiwan (Controls unexposed, sick), 2026 Razaz_Sweden, 2026 Meng_Norway (Controls unexposed, sick), 2026
5
1.02
[
0.87
; 1.20]
43,031
6,792
not evaluable
Language disorders/delay
Botton, 2025 Meng_Norway (Controls unexposed, sick), 2026 Meng_Taiwan (Controls unexposed, sick), 2026
3
1.28
[
1.05
; 1.57]
43,280
4,331
not evaluable
Cognitive developmental disorders/delay (> 6 years old)
Christensen (Controls exposed to LTG/LEV), 2024 Botton, 2025 Razaz_Sweden, 2026 Meng_Taiwan (Controls unexposed, sick), 2026
4
1.35
[
0.93
; 1.95]
4,987
6,488
not evaluable
Severe cognitive developmental delay (Mental retardation) (> 6 years old)
Christensen (Controls exposed to LTG/LEV), 2024 Botton, 2025 Razaz_Sweden, 2026 Meng_Taiwan (Controls unexposed, sick), 2026
4
1.35
[
0.93
; 1.95]
4,987
6,488
not evaluable
Learning disorders
Botton, 2025 Meng_Taiwan (Controls unexposed, sick), 2026
2
1.08
[
0.78
; 1.49]
2,531
4,027
not evaluable
Psychomotor developmental disorders/delay
Meng_Taiwan (Controls unexposed, sick), 2026
1
1.25
[
0.92
; 1.69]
27,327
543
not evaluable
Cognitive developmental disorders/delay (3-6 years old)
Razaz_Norway, 2026
1
1.58
[
0.27
; 9.30]
5
460
not evaluable
Severe cognitive developmental delay (Mental retardation) (3-6 years old)
Razaz_Norway, 2026
1
1.58
[
0.27
; 9.30]
5
460
not evaluable
0.2
10.0
1.0
