Valproate (All indications) updated on 04-22-2025

Club foot / Talipes equinovarus

id	Study   Auto Kim (Controls exposed to LTG) (Valproate) (Indications NOS), 2026Kim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023Blotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019Källén (Valproate) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013	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 trimesterPaternal 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	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.
S19424 R82745	Kim (Controls exposed to LTG) (Valproate) (Indications NOS), 2026	Talipes equinovarus	1st trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.77 [0.24;2.43] C excluded (control group)	5/667   7/718	12	667		ref
S19425 R82756	Kim (Controls unexposed, NOS) (Valproate) (Indications NOS), 2026	Talipes equinovarus	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	1.40 [0.57;3.41]	5/667   18,372/2,489,078	18,377	667		ref
S15201 R62353	Cohen (Valproate) (Mixed indications) (Controls unexposed, NOS), 2023	Clubfoot	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	5.04 [3.55;7.15]	-/2,031   -/4,866,362	-	2,031		ref
S10174 R37223	Blotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019	Talipes equinovarus	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	0.66 [0.03;13.68] C excluded (control group)	0/913   2/2,997	2	913		ref
S10051 R36497	Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019	Talipes equinovarus	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	0.61 [0.04;9.80] C	0/913   1,677/1,875,733	1,677	913		ref
S9309 R32429	Källén (Valproate) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013	Pes equinovarus	early pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	9.40 [1.13;78.28] C excluded (control group)	6/697   1/1,084	7	697		ref
S9310 R32437	Källén (Valproate) (Controls unexposed, NOS) (Indications NOS), 2013	Pes equinovarus	early pregnancy	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	6.12 [2.25;13.30]	6/697   2,127/1,575,847	2,133	697		ref
					Total	4 studies	3.26 [1.49;7.13]		22,187	4,308
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 9309, 10174, 19424

Umbrella review (other published meta-analyses)