Levetiracetam (All indications)

Spina bifida

id	Study   Auto Blotière (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019Veiby (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2014Veiby (Levetiracetam) (Controls unexposed, sick), 2014Vajda (Levetiracetam) (Controls unexposed, sick), 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 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.
S10170 R37109	Blotière (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019	Spina bifida	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	1.73 [0.07;42.42] C excluded (control group)	0/579   1/2,997	1	579		ref
S10037 R36194	Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019	Spina bifida	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	2.63 [0.16;42.13] C	0/579   616/1,875,733	616	579		ref
S8998 R30564	Veiby (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2014	Spina bifida	throughout pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Partial overlapping	5.22 [0.10;264.46] C excluded (control group)	0/114   0/593	0	114		ref
S9000 R30569	Veiby (Levetiracetam) (Controls unexposed, sick), 2014	Spina bifida	throughout pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: No	4.74 [0.24;92.40] C	0/114   3/3,773	3	114		ref
S9829 R35237	Vajda (Levetiracetam) (Controls unexposed, sick), 2013	Spina bifida	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.34 [0.05;119.47] C	0/63   0/147	0	63		ref
					Total	3 studies	3.19 [0.53;19.33]		619	756
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 8998, 10170