Valproate (Epilepsy) updated on 04-22-2025

ADHD (Attention deficit hyperactivity disorder): Diagnosis

id	Study   Auto Madley-Dowd_SE (Valproate) (Controls exposed to LTG), 2024Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024Madley-Dowd_UK (Valproate) (Controls exposed to LTG) (Epilepsy), 2024Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024Dreier (Valproate) (Epilepsy) (Controls exposed to LTG), 2023Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023Huber-Mollema (Valproate), 2019Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013Bromley (Valproate) (Controls unexposed, disease free), 2013Bromley (Valproate) (Controls unexposed, sick), 2013Cohen (Valproate), 2013Adab (Valproate), 2004	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimester	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S17439 R73280	Madley-Dowd_SE (Valproate) (Controls exposed to LTG), 2024	Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Partial overlapping	3.47 [2.63;4.58] C excluded (control group)	113/792   109/2,383	222	792		ref
S17440 R73286	Madley-Dowd_SE (Valproate) (Controls unexposed, sick), 2024	Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes Partial overlapping	1.21 [0.99;1.47]	113/792   929/10,769	1,042	792		ref
S17261 R72232	Madley-Dowd_UK (Valproate) (Controls exposed to LTG) (Epilepsy), 2024	Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median follow up 9.32 (5.54-12.83) years old	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	1.28 [0.53;3.09] C excluded (control group)	8/354   14/791	22	354		ref
S17256 R72221	Madley-Dowd_UK (Valproate) (Controls unexposed, sick) (Epilepsy), 2024	Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - Median follow up 9.32 (5.54-12.83) years old	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes	1.50 [0.62;3.63]	8/354   38/4,075	46	354		ref
S15877 R65465	Dreier (Valproate) (Epilepsy) (Controls exposed to LTG), 2023	Attention-deficit/hyperactivity disorder (ADHD) - Corresponding ICD-10 F-chapter - Up to 22 years of age	during pregnancy (anytime or not specified)	population based cohort propective	exposed to other treatment, sick excluded	Adjustment: No	3.14 [2.37;4.16] C excluded (control group)	106/1,952   95/5,288	201	1,952		ref
S15878 R65479	Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023	Attention-deficit/hyperactivity disorder (ADHD) - Corresponding ICD-10 F-chapter - Up to 22 years of age	during pregnancy (anytime or not specified)	population based cohort propective	unexposed, sick	Adjustment: Yes	1.41 [1.10;1.81]	106/1,952   528/22,203	634	1,952		ref
S7508 R22470	Huber-Mollema (Valproate), 2019	Diagnosis of ADHD	throughout pregnancy	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.38 [0.25;7.58] C	2/26   5/88	7	26		ref
S6662 R18419	Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013	Attention deficit hyperactivity disorder (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.60 [0.01;30.84] C excluded (control group)	0/50   0/30	0	50		ref
S6659 R18407	Bromley (Valproate) (Controls unexposed, disease free), 2013	Attention deficit hyperactivity disorder (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No	4.31 [0.08;220.05] C excluded (control group)	0/50   0/214	0	50		ref
S6602 R18104	Bromley (Valproate) (Controls unexposed, sick), 2013	Attention deficit hyperactivity disorder (at 6 years old)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No	0.52 [0.01;26.73] C	0/50   0/26	0	50		ref
S7295 R21116	Cohen (Valproate), 2013	Children with either ADHD inattentive OR combined types > 1 SD (from the Attention Problems and Hyperactivity scales of the BASC) (Both Parent and Teacher)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.84 [0.46;7.35] C	6/28   4/31	10	28		ref
S7175 R27087	Adab (Valproate), 2004	Attention deficit hyperactivity disorder	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No	8.31 [0.39;175.93] C	2/63   0/101	2	63		ref
					Total	7 studies	1.30 [1.12;1.51]		1,741	3,265
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 6662, 6659, 15877, 17439, 17261

Umbrella review (other published meta-analyses)