Valproate (Epilepsy)

Table   Graphic  
individual studies
OutcomeTE95% CIn casesn exposedkPub. 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 Samrén (Valproate), 1999 Kaneko (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 Mawer (Valproate) (Controls unexposed, sick), 2010 Bànhidy (Valproate), 2011 Charlton (Valproate) (Controls unexposed, sick), 2011 Arteaga-Vázquez (Valproate), 2012 Hernández-Díaz (Valproate) (Controls unexposed, disease free), 2012 Cassina (Valproate) (Controls unexposed, disease free), 2013 Campbell (Valproate) (Controls unexposed, sick), 2014 Veiby (Valproate) (Controls unexposed, sick), 2014 Vanya (Valproate) (Controls unexposed, sick), 2015 Petersen (Valproate) (Controls unexposed, sick), 2017 Putignano (Valproate), 2019 Zhang (Valproate), 2020 Alsaadi (Controls unexposed sick), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Thomas (Valproate) (Controls unexposed, sick), 2021 Hosny (Valproate) (Controls unexposed, sick), 2021 Battino, 2024 Wiggs, 2024 Vajda b (Valproate) (Epilepsy) (Controls unexposed, sick), 2024 Hao (Controls unexposed, sick), 2025 323.15[2.67; 3.72]1,0746,035low Major congenital malformations Jäger-Roman (Valproate), 1986 Robert (Valproate), 1986 Canger (Valproate), 1999 Samrén (Valproate), 1999 Hvas (Valproate) (Controls unexposed, sick), 2000 Dean (Valproate), 2002 Kaaja (Valproate), 2003 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Mawer (Valproate) (Controls unexposed, sick), 2010 Bànhidy (Valproate), 2011 Charlton (Valproate) (Controls unexposed, sick), 2011 Hernández-Díaz (Valproate) (Controls unexposed, disease free), 2012 Cassina (Valproate) (Controls unexposed, disease free), 2013 Campbell (Valproate) (Controls unexposed, sick), 2014 Veiby (Valproate) (Controls unexposed, sick), 2014 Vanya (Valproate) (Controls unexposed, sick), 2015 Petersen (Valproate) (Controls unexposed, sick), 2017 Zhang (Valproate), 2020 Alsaadi (Controls unexposed sick), 2020 Thomas (Valproate) (Controls unexposed, sick), 2021 Hosny (Valproate) (Controls unexposed, sick), 2021 Battino, 2024 Wiggs, 2024 Vajda b (Valproate) (Epilepsy) (Controls unexposed, sick), 2024 Hao (Controls unexposed, sick), 2025 253.00[2.46; 3.66]8905,587low Congenital heart defects D'Souza (Valproate) (Controls unexposed, sick), 1991 Canger (Valproate), 1999 Artama (Valproate), 2005 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 Thomas (Valproate) (Controls unexposed, sick), 2021 Wiggs, 2024 112.88[1.91; 4.33]1444,526low Limb defects Artama (Valproate), 2005 Mawer (Valproate) (Controls unexposed, sick), 2010 Vajda (Valproate) (Controls unexposed, sick), 2013 De Jonge (Valproate), 2013 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Thomas (Valproate) (Controls unexposed, sick), 2021 Wiggs, 2024 72.52[1.76; 3.61]2262,807not 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 79.34[4.08; 21.40]523,298not 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 Christensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 61.09[0.82; 1.46]8002,152not evaluable Hypospadias D'Souza (Valproate) (Controls unexposed, sick), 1991 Bànhidy (Valproate), 2011 Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2018 54.64[2.00; 10.77]642,933not evaluable Spina bifida Czeizel (Valproate), 1992 Artama (Valproate), 2005 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Charlton (Valproate) (Controls unexposed, sick), 2011 49.14[2.63; 31.73]14518not evaluable Minor congenital malformations Robert (Valproate), 1986 Battino (Valproate), 1992 Dean (Valproate), 2002 Alsaadi (Controls unexposed sick), 2020 44.84[2.06; 11.36]43106not evaluable Oro-facial clefts Hernández-Díaz (Valproate) (Controls exposed to Lamotrigine, sick), 2012 De Jonge (Valproate), 2013 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2018 Wiggs, 2024 53.44[1.86; 6.37]3293,613not evaluable Polydactyly D'Souza (Valproate) (Controls unexposed, sick), 1991 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 Bànhidy (Valproate), 2011 Tomson (Valproate), 2018 44.37[0.52; 36.93]101,415not evaluable Urinary malformations Artama (Valproate), 2005 Tomson (Valproate), 2018 Thomas (Valproate) (Controls unexposed, sick), 2021 Wiggs, 2024 41.36[0.71; 2.59]262,609not evaluable Digestive system anomalies Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Thomas (Valproate) (Controls unexposed, sick), 2021 Wiggs, 2024 31.44[0.79; 2.62]162,185not evaluable Nervous system anomalies De Jonge (Valproate), 2013 Thomas (Valproate) (Controls unexposed, sick), 2021 Wiggs, 2024 37.35[2.65; 20.39]211996not evaluable Genital anomalies Artama (Valproate), 2005 De Jonge (Valproate), 2013 Wiggs, 2024 34.93[3.28; 7.42]324922not evaluable Chromosomal abnormalities Artama (Valproate), 2005 Wiggs, 2024 22.66[0.64; 11.11]1887not evaluable Cleft lip with or without cleft palate Artama (Valproate), 2005 Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 27.19[1.57; 32.82]7291not evaluable Craniosynostosis D'Souza (Valproate) (Controls unexposed, sick), 1991 115.00[0.12; 1923.88]-1not evaluable Down syndrom / Trisomy 21 D'Souza (Valproate) (Controls unexposed, sick), 1991 115.00[0.12; 1923.88]-1not evaluable Eye defects Dean (Valproate), 2002 Artama (Valproate), 2005 20.45[0.12; 1.72]10309not evaluable Hip dislocation and/or dysplasia D'Souza (Valproate) (Controls unexposed, sick), 1991 115.00[0.12; 1923.88]-1not evaluable Valproate syndrome 0----- Cleft palate Viinikainen (Valproate) (Controls unexposed, sick) a, 2006 11.87[0.04; 96.99]-28not evaluable Ear, face and neck anomalies Artama (Valproate), 2005 10.71[0.03; 14.91]2263not evaluable Eye, ear, face and neck malformations Wiggs, 2024 11.03[0.41; 2.59]-624not evaluable Respiratory system anomalies Wiggs, 2024 14.16[1.88; 9.20]-624not 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 Arkilo (Valproate), 2015 Cohen (Valproate) (Controls unexposed NOS), 2019 Putignano (Valproate), 2019 Coste (Valproate) (Controls unexposed, NOS), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Leite, 2024 141.21[1.02; 1.42]252,2522,056low Small for gestational age (weight) Endo (Valproate) (Controls unexposed, sick), 2004 Burja (Valproate) (Controls unexposed, sick), 2006 Pennell (Valproate), 2012 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Putignano (Valproate), 2019 Cohen (Valproate) (Controls unexposed NOS), 2019 Coste (Valproate) (Controls unexposed, NOS), 2020 Aydin (Valproate) (Controls unexposed, sick), 2020 Christensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 91.47[1.04; 2.06]211,9593,195not evaluable Low birth weight (< 2500g) Kini (Valproate) (Controls unexposed, sick), 2006 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Coste (Valproate) (Controls unexposed, NOS), 2020 Christensen (Valproate) (Epilepsy) (Controls unexposed, general population), 2024 41.35[0.95; 1.93]92,6773,047not evaluable Large for gestational age (weight) Artama (Valproate) (Controls unexposed, sick), 2013 Putignano (Valproate), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020 31.21[0.74; 1.98]158845not evaluable Macrosomia (> 4000g) Endo (Valproate) (Controls unexposed, sick), 2004 Kini (Valproate) (Controls unexposed, sick), 2006 Coste (Valproate) (Controls unexposed, NOS), 2020 30.91[0.55; 1.51]577,4071,059not evaluable Very preterm (28 to 32 weeks) Coste (Valproate) (Controls unexposed, NOS), 2020 11.21[0.54; 2.70]8,590991not evaluable Extremely preterm (< 28 weeks) Coste (Valproate) (Controls unexposed, NOS), 2020 10.85[0.12; 6.01]2,042991not evaluable Large head circumference for gestational age Díaz-Romero (Valproate), 1999 10.79[0.01; 44.65]-10not evaluable Maternal consequences Caesarean Endo (Valproate) (Controls unexposed, sick), 2004 Borthen (Valproate) (Controls unexposed, sick), 2010 Artama (Valproate) (Controls unexposed, sick), 2013 30.93[0.76; 1.14]831926not evaluable Preeclampsia Borthen (Valproate) (Controls unexposed, sick), 2011 Cohen (Valproate) (Controls unexposed NOS), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020 31.43[0.81; 2.51]53,63830not evaluable Assisted deliveries (forceps, vacuum, ...) Endo (Valproate) (Controls unexposed, sick), 2004 Borthen (Valproate) (Controls unexposed, sick), 2010 21.18[0.73; 1.90]177220not evaluable Postpartum hemorrhage Borthen (Valproate) (Controls unexposed, sick), 2010 11.44[1.01; 2.06]319215not evaluable Abruptio placentae (retroplacental hematoma) Cohen (Valproate) (Controls unexposed NOS), 2019 10.63[0.19; 2.09]20,260-not evaluable Amniotic fluid problems (polyhydramnios and/or oligohydramnios) Aydin (Valproate) (Controls unexposed, sick), 2020 12.05[0.04; 110.56]-11not evaluable Gestational diabetes Aydin (Valproate) (Controls unexposed, sick), 2020 10.65[0.02; 17.40]111not evaluable Maternal consequences (as a whole) Alsfouk (Valproate), 2022 Razaz (Valproate), 2024 21.69[1.28; 2.25]7421,907not evaluable Polyhydramnios Endo (Valproate) (Controls unexposed, sick), 2004 10.11[0.00; 14.76]-5not 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 Putignano (Valproate), 2019 51.78[0.92; 3.45]63683not 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 Putignano (Valproate), 2019 Aydin (Valproate) (Controls unexposed, sick), 2020 52.01[1.54; 2.62]2,092771not evaluable Low Apgar score (< 7) (at 1 min) Endo (Valproate) (Controls unexposed, sick), 2004 Pennell (Valproate), 2012 Artama (Valproate) (Controls unexposed, sick), 2013 32.54[0.71; 9.05]132667not evaluable Feeding difficulty D'Souza (Valproate) (Controls unexposed, sick), 1991 Burja (Valproate) (Controls unexposed, sick), 2006 224.38[1.49; 397.73]23not evaluable Neonatal disorders (as a whole) D'Souza (Valproate) (Controls unexposed, sick), 1991 Coste (Valproate) (Controls unexposed, NOS), 2020 20.92[0.76; 1.11]222,323992not evaluable Neonatal intracranial hemorrhage D'Souza (Valproate) (Controls unexposed, sick), 1991 Burja (Valproate) (Controls unexposed, sick), 2006 215.00[1.09; 206.94]33not evaluable Withdrawal syndrome / Neonatal abstinence syndrome / Poor neonatal adaptation Burja (Valproate) (Controls unexposed, sick), 2006 1Out of scale189.00[2.70; 13229.55]12not evaluable Fetal distress McVearry (Valproate), 2009 10.09[0.00; 1.83]416not evaluable Jaundice / Icterus D'Souza (Valproate) (Controls unexposed, sick), 1991 14.33[0.06; 320.42]11not evaluable Neonatal hypotonia D'Souza (Valproate) (Controls unexposed, sick), 1991 115.00[0.12; 1923.88]-1not evaluable Neonatal infections D'Souza (Valproate) (Controls unexposed, sick), 1991 115.00[0.12; 1923.88]-1not evaluable Neonatal tachypnea D'Souza (Valproate) (Controls unexposed, sick), 1991 115.00[0.12; 1923.88]-1not evaluable Very low Apgar score (< 5) (at 1 min) 0----- Long term consequences Child/Infant death (> 28 days of life) Artama (Valproate) (Controls unexposed, sick), 2013 Coste (Valproate) (Controls unexposed, NOS), 2020 23.01[1.62; 5.60]4,7141,694not evaluable Child/Infant growth abnormalities (> 1 year) Pennell (Valproate), 2012 10.24[0.03; 2.07]744not evaluable Child/Infant head circumference abnormalities (> 1 year) Pennell (Valproate), 2012 11.39[0.03; 71.26]-42not evaluable Child/Infant lenght abnormalities (> 1 year) Kini (Valproate) (Controls unexposed, sick), 2006 12.55[0.69; 9.43]1063not evaluable Child/Infant weight abnormalities (> 1 year) Kini (Valproate) (Controls unexposed, sick), 2006 11.16[0.35; 3.82]1263not 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 a (Valproate) (Controls unexposed sick), 2024 71.42[0.99; 2.03]4623,046not evaluable Early intrauterine deaths (< 22 weeks) / Spontaneous abortions Babic (Valproate), 2014 Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Tomson (Valproate), 2015 Arkilo (Valproate), 2015 Miškov (Valproate) (Controls unexposed, sick), 2016 Alsaadi (Controls unexposed sick), 2020 61.04[0.84; 1.29]3692,499not evaluable Late intrauterine deaths (> 22 weeks) / Stillbirths Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 Arkilo (Valproate), 2015 Tomson (Valproate), 2015 Aydin (Valproate) (Controls unexposed, sick), 2020 AlSheikh (Valproate) (Controls unexposed, sick), 2020 51.83[1.01; 3.31]422,475not 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 31.83[0.80; 4.17]211,304not evaluable Perinatal death Canger (Valproate), 1999 Artama (Valproate) (Controls unexposed, sick), 2013 Tomson (Valproate), 2015 32.16[0.95; 4.89]271,833not evaluable Therapeutic terminations of pregnancy Miškov (Valproate) (Controls unexposed, sick), 2016 10.64[0.01; 40.08]-6not evaluable Ectopic pregnancy Campbell (Valproate) (Controls exposed to Lamotrigine, sick), 2014 11.70[0.03; 85.94]-1,290not evaluable Neuro-developmental disorders Language disorders/delay Adab (Valproate), 2004 Gaily (Valproate) (Controls unexposed, sick), 2004 Eriksson (Valproate), 2005 Shallcross (Valproate), 2011 Nadebaum (Valproate), 2011 Meador (Valproate), 2013 Baker (Valproate) (Controls unexposed, sick), 2015 Videman (Valproate) (Controls unexposed, disease free), 2016 Bromley (Valproate), 2016 Deshmukh (Valproate), 2016 Kasradze (Valproate) (Controls unexposed, disease free), 2017 Husebye (Valproate) (Controls unexposed, sick), 2020 Coste (Valproate) (Controls unexposed, NOS), 2020 Thomas a (Valproate), 2022 Stjerna (Valproate) (Epilepsy), 2024 152.94[2.10; 4.11]72,2491,419critical ASD (Autism spectrum disorder): Diagnosis/Risk Adab (Valproate), 2004 Bromley (Valproate) (Controls unexposed, sick), 2013 Wood (Valproate), 2015 Bjørk (Valproate) (Controls unexposed, sick), 2018 Huber-Mollema (Valproate), 2019 Coste (Valproate) (Controls unexposed, NOS), 2020 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Hernandez-Diaz (Valproate) (Epilepsy) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024 Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024 102.48[1.95; 3.15]5,4784,842low Cognitive developmental disorders/delay (> 6 years old) Adab (Valproate), 2004 Gaily (Valproate) (Controls unexposed, sick), 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 Thomas a (Valproate), 2022 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Stjerna (Valproate) (Epilepsy), 2024 Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024 Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024 142.58[2.13; 3.12]5573,437low ASD (Autism spectrum disorder): Diagnosis Adab (Valproate), 2004 Bromley (Valproate) (Controls unexposed, sick), 2013 Wood (Valproate), 2015 Huber-Mollema (Valproate), 2019 Coste (Valproate) (Controls unexposed, NOS), 2020 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Hernandez-Diaz (Valproate) (Epilepsy) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024 Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024 92.54[2.00; 3.23]5,4484,815not evaluable ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk Adab (Valproate), 2004 Viinikainen (Valproate) b, 2006 Cohen (Valproate), 2013 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Bromley (Valproate) (Controls unexposed, sick), 2013 Bromley (Valproate), 2016 Huber-Mollema (Valproate), 2019 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024 Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024 101.28[1.10; 1.48]1,7503,343low 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 Arkilo (Valproate), 2015 Charlton (Valproate), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020 Bjørk (Valproate) (Controls unexposed, sick), 2022 93.24[2.20; 4.79]10,7853,173not evaluable ADHD (Attention deficit hyperactivity disorder): Diagnosis Adab (Valproate), 2004 Bromley (Valproate) (Controls unexposed, sick), 2013 Cohen (Valproate), 2013 Huber-Mollema (Valproate), 2019 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024 Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024 71.30[1.12; 1.51]1,7413,265not evaluable Psychomotor developmental disorders/delay Koch (Valproate), 1996 Adab (Valproate), 2004 Viinikainen (Valproate) b, 2006 Cohen (Valproate), 2011 Shallcross (Valproate), 2011 Bromley (Valproate) (Controls unexposed, sick), 2013 Deshmukh (Valproate), 2016 Videman (Valproate) (Controls unexposed, disease free), 2016 Thomas b (Controls unexposed, sick), 2022 92.61[1.80; 3.79]46483not 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 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024 Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024 82.77[2.23; 3.44]5383,217not 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 Deshmukh (Valproate), 2016 Kasradze (Valproate) (Controls unexposed, disease free), 2017 Coste (Valproate) (Controls unexposed, NOS), 2020 66.12[3.14; 11.91]3,4661,170not evaluable Cognitive developmental disorders/delay (< 3 years old) Bromley (Valproate) (Controls unexposed, sick), 2010 Shallcross (Valproate), 2011 Meador (Valproate), 2013 Videman (Valproate) (Controls unexposed, disease free), 2016 Thomas b (Controls unexposed, sick), 2022 54.09[2.17; 7.69]64330not evaluable ADHD (Attention deficit hyperactivity disorder): Risk Viinikainen (Valproate) b, 2006 Veiby (Valproate) (Controls unexposed, sick) b, 2013 Cohen (Valproate), 2013 Bromley (Valproate), 2016 Huber-Mollema (Valproate), 2019 51.15[0.68; 1.96]32149not 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 45.02[3.12; 8.08]3,4261,101not evaluable ASD (Autism spectrum disorder): Risk Wood (Valproate), 2015 Bjørk (Valproate) (Controls unexposed, sick), 2018 Huber-Mollema (Valproate), 2019 31.28[0.48; 3.42]3779not evaluable Learning disorders Ren (Valproate) (Epilepsy), 2023 11.34[0.99; 1.81]-172not evaluable Severe cognitive developmental delay (Mental retardation) (< 3 years old) Meador (Valproate), 2013 13.29[1.00; 10.85]1329not evaluable0.0100.01.0