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

Caesarean

id	Study   Auto Mazzone (Valproate) (Controls exposed to LTG) (Mixed indications), 2025Mazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013Artama (Valproate) (Controls unexposed, disease free), 2013Artama (Valproate) (Controls unexposed, sick), 2013Rihtman (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2013Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013Borthen (Valproate) (Controls exposed to Lamotrigine, sick), 2010Borthen (Valproate) (Controls unexposed, disease free), 2010Borthen (Valproate) (Controls unexposed, sick), 2010Endo (Valproate) (Controls unexposed, disease free), 2004Endo (Valproate) (Controls unexposed, sick), 2004Jäger-Roman (Valproate), 1986	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.
S18706 R79587	Mazzone (Valproate) (Controls exposed to LTG) (Mixed indications), 2025	Cesarean section	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.01 [0.78;1.31] C excluded (control group)	104/315   482/1,469	586	315		ref
S18708 R79603	Mazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025	Cesarean section	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	0.97 [0.67;1.40]	104/315   186,309/624,794	186,413	315		ref
S9283 R32206	Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013	Caesarean section	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.96 [0.62;1.47] C excluded (control group)	126/706   32/173	158	706		ref
S9284 R32218	Artama (Valproate) (Controls unexposed, disease free), 2013	Caesarean section	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.16 [0.96;1.42] excluded (control group)	126/706   114,791/721,948	114,917	706		ref
S9285 R32230	Artama (Valproate) (Controls unexposed, sick), 2013	Caesarean section	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes	0.93 [0.73;1.18]	126/706   331/1,800	457	706		ref
S9450 R33184	Rihtman (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2013	Cesarean section	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No Controls: epilepsy indication	1.80 [0.53;6.08] C excluded (control group)	7/29   6/40	13	29		ref
S9451 R33219	Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013	Cesarean section	at least 1st trimester excluded	prospective cohort	unexposed (general population or NOS)	Adjustment: No	3.74 [0.99;14.12] C excluded (exposition period)	7/29   4/51	11	29		ref
S9432 R33123	Borthen (Valproate) (Controls exposed to Lamotrigine, sick), 2010	Caesarean	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.89 [0.55;1.45] C excluded (control group)	37/215   44/233	81	215		ref
S9434 R33131	Borthen (Valproate) (Controls unexposed, disease free), 2010	Caesarean	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.70 [1.20;2.40] excluded (control group)	37/215   51,806/362,302	51,843	215		ref
S9436 R33139	Borthen (Valproate) (Controls unexposed, sick), 2010	Caesarean	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: No	0.94 [0.65;1.37] C	37/215   337/1,863	374	215		ref
S9300 R32376	Endo (Valproate) (Controls unexposed, disease free), 2004	Cesarean section	at least 1st trimester	retrospective cohort	unexposed, disease free excluded	Adjustment: No	0.87 [0.05;16.27] C excluded (control group)	0/5   74/656	74	5		ref
S9301 R32391	Endo (Valproate) (Controls unexposed, sick), 2004	Cesarean section	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No	0.11 [0.00;14.76] C	0/5   0/1	0	5		ref
S9308 R32419	Jäger-Roman (Valproate), 1986	Caesarean section	at least 1st trimester excluded	prospective cohort	unexposed (general population or NOS)	Adjustment: No	5.40 [1.38;21.12] C excluded (exposition period)	4/14   8/116	12	14		ref
					Total	4 studies	0.94 [0.79;1.12]		187,244	1,241
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 9300, 9432, 9434, 9283, 9284, 9450, 18706