Topiramate (All indications)

Congenital heart defects

id	Study   Auto Thomas (Topiramate) (Controls exposed to Lamotrigine, sick), 2021Thomas (Topiramate) (Controls unexposed, sick), 2021Tomson (Topiramate), 2018Vajda (Topiramate) (Controls exposed to Lamotrigine, sick), 2013Vajda (Topiramate) (Controls unexposed, sick), 2013Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006	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.
S12873 R48624	Thomas (Topiramate) (Controls exposed to Lamotrigine, sick), 2021	Cardiac malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.90 [0.07;50.68] C excluded (control group)	0/9   1/50	1	9		ref
S12875 R48636	Thomas (Topiramate) (Controls unexposed, sick), 2021	Cardiac malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.05 [0.11;38.10] C	0/9   9/340	9	9		ref
S8575 R28526	Tomson (Topiramate), 2018	Cardiac malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	3.35 [0.96;11.71] C	3/152   15/2,514	18	152		ref
S10297 R37721	Vajda (Topiramate) (Controls exposed to Lamotrigine, sick), 2013	Cardiac Malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.02 [0.05;20.14] C excluded (control group)	0/44   3/315	3	44		ref
S10298 R37731	Vajda (Topiramate) (Controls unexposed, sick), 2013	Cardiac Malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.11 [0.04;27.86] C	0/44   1/147	1	44		ref
S10221 R37445	Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2012	Cardiovascular anomalies	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.45 [0.15;14.00] C	1/359   3/1,562	4	359		ref
S8569 R28510	Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006	Cardiac	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	2.60 [0.14;49.43] C	0/28   4/647	4	28		ref
					Total	5 studies	2.47 [0.98;6.24]		36	592
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 10297, 12873