Ethosuximide (Epilepsy)

Major congenital malformations

id	Study   Auto Vajda (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2019Vajda (Ethosuximide) (Controls unexposed, sick), 2019Tomson (Ethosuximide), 2018Bànhidy (Ethosuximide), 2011Morrow (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2006Morrow (Ethosuximide) (Controls unexposed, sick), 2006Kaaja (Ethosuximide), 2003Dean (Ethosuximide), 2002Samrén (Ethosuximide), 1999	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.
S7792 R23010	Vajda (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2019	Fetal malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	2.09 [0.11;40.14] C excluded (control group)	0/5   20/406	20	5		ref
S7793 R23011	Vajda (Ethosuximide) (Controls unexposed, sick), 2019	Fetal malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	3.44 [0.16;72.20] C	0/5   5/176	5	5		ref
S7645 R22621	Tomson (Ethosuximide), 2018	Malformed Offspring	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.42 [0.08;24.39] C	0/12   74/2,514	74	12		ref
S6495 R17815	Bànhidy (Ethosuximide), 2011	Total congenital abnormalities	throughout pregnancy	case control	unexposed, sick	Adjustment: No Matched	4.13 [0.18;96.94] C	2/2   12/22	14	2		ref
S6065 R15773	Morrow (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2006	Major congenital malformation	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.26 [0.07;22.17] C excluded (control group)	0/12   21/647	21	12		ref
S6066 R15780	Morrow (Ethosuximide) (Controls unexposed, sick), 2006	Major congenital malformation	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.12 [0.06;20.58] C	0/12   8/227	8	12		ref
S6142 R16036	Kaaja (Ethosuximide), 2003	Major malformation	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	31.53 [1.02;978.23] C	0/2   2/239	2	2		ref
S6683 R18561	Dean (Ethosuximide), 2002	Major congenital malformations	at least 1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	2.03 [0.08;51.22] C	0/4   2/38	2	4		ref
S6713 R18986	Samrén (Ethosuximide), 1999	Major congenial abnormalities	at least 1st trimester	retrospective cohort	unexposed, disease free	Adjustment: No Matched	3.93 [0.22;69.67] C	0/9   29/2,000	29	9		ref
					Total	7 studies	3.13 [0.99;9.93]		134	46
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 6065, 7792