Valproate (Epilepsy)

Low Apgar score (< 7) (at 1 min)

id	Study   Auto Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013Artama (Valproate) (Controls unexposed, disease free), 2013Artama (Valproate) (Controls unexposed, sick), 2013Pennell (Valproate), 2012Endo (Valproate) (Controls unexposed, disease free), 2004Endo (Valproate) (Controls unexposed, sick), 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 specifiedwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S5931 R15126	Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013	1-min Apgar <7	3rd trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.31 [0.62;2.73] C excluded (control group)	45/600   9/154	54	600		ref
S5911 R14905	Artama (Valproate) (Controls unexposed, disease free), 2013	1-min Apgar <7	3rd trimester	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.76 [1.29;2.39] excluded (control group)	45/600   27,939/689,482	27,984	600		ref
S5919 R15001	Artama (Valproate) (Controls unexposed, sick), 2013	1-min Apgar <7	3rd trimester	population based cohort retrospective	unexposed, sick	Adjustment: Yes	1.78 [1.20;2.66]	45/600   69/1,708	114	600		ref
S6416 R17616	Pennell (Valproate), 2012	Apgar score (at 1 minute < 7)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick	Adjustment: No	6.78 [2.12;21.73] C	14/62   4/97	18	62		ref
S8221 R25744	Endo (Valproate) (Controls unexposed, disease free), 2004	Apgar score (<8 at 1min)	at least 1st trimester	retrospective cohort	unexposed, disease free excluded	Adjustment: No	0.54 [0.03;10.27] C excluded (control group)	0/5   47/280	47	5		ref
S8311 R26301	Endo (Valproate) (Controls unexposed, sick), 2004	Apgar score (<8 at 1min)	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No	0.11 [0.00;14.76] C	0/5   0/1	0	5		ref
					Total	3 studies	2.54 [0.71;9.05]		132	667
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 8221, 5931, 5911