Lamotrigine (All indications)

Low birth weight (< 2500g)

id	Study   Auto Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Hernández-Díaz (Lamotrigine) (Mixed indications), 2014Kilic (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2014Kilic (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2014Artama (Lamotrigine) (Controls unexposed, disease free), 2013Artama (Lamotrigine) (Controls unexposed, sick), 2013Veiby (Lamotrigine) (Controls unexposed, disease free) b, 2013Veiby (Lamotrigine) (Controls unexposed, sick) b, 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.
S8978 R30432	Coste (Lamotrigine) (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	1.15 [0.99;1.35] C	172/2,813   91,172/1,707,707	91,344	2,813		ref
S8974 R30418	Hernández-Díaz (Lamotrigine) (Mixed indications), 2014	Low birth weight (< 2500g)	throughout pregnancy	prospective cohort	unexposed, disease free	Adjustment: No	1.20 [0.71;2.03] C	74/1,581   18/457	92	1,581		ref
S8975 R30420	Kilic (Lamotrigine) (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: Yes	1.30 [1.00;1.80] excluded (control group)	48/876   23,503/673,844	23,551	876		ref
S8976 R30423	Kilic (Lamotrigine) (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	1.17 [0.85;1.61] C	48/876   249/5,275	297	876		ref
S8902 R30063	Artama (Lamotrigine) (Controls unexposed, disease free), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	0.99 [0.43;2.25] excluded (control group)	6/173   21,546/719,509	21,552	173		ref
S8903 R30075	Artama (Lamotrigine) (Controls unexposed, sick), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes	0.96 [0.39;2.34]	6/173   65/1,793	71	173		ref
S8953 R30312	Veiby (Lamotrigine) (Controls unexposed, disease free) b, 2013	Low birth weight (< 2500 grams)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: Yes	1.20 [0.50;2.80] excluded (control group)	6/103   5,024/106,899	5,030	103		ref
S8954 R30326	Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013	Low birth weight (< 2500 grams)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No	1.43 [0.55;3.75] C	6/103   16/386	22	103		ref
					Total	5 studies	1.16 [1.02;1.32]		91,826	5,546
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 8902, 8953, 8975