Topiramate (All indications)

Low birth weight (< 2500g)

id	Study   Auto Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Hernández-Díaz (Topiramate) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2014Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014	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.
S10103 R36815	Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020	Weight at birth <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	1.10 [0.74;1.62] C excluded (control group)	32/477   179/2,916	211	477		ref
S8613 R28733	Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020	Weight at birth <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	1.27 [0.89;1.82] C	32/477   91,455/1,710,441	91,487	477		ref
S8599 R28628	Hernández-Díaz (Topiramate) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2014	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.86 [1.19;2.90] C excluded (control group)	29/347   74/1,581	103	347		ref
S8600 R28631	Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free	Adjustment: No	2.22 [1.21;4.08] C	29/347   18/457	47	347		ref
S8608 R28700	Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.25 [0.44;3.61] C excluded (control group)	4/59   48/876	52	59		ref
S8609 R28703	Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: No	2.01 [0.73;5.55] C excluded (control group)	4/59   23,503/673,844	23,507	59		ref
S8610 R28706	Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: No Controls: epilepsy indication	1.47 [0.53;4.08] C	4/59   249/5,275	253	59		ref
					Total	3 studies	1.51 [1.06;2.15]		91,787	883
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 8599, 8608, 8609, 10103