Phenytoin (All indications)

Low birth weight (< 2500g)

id	Study   Auto Kilic (Phenytoin) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Kilic (Phenytoin) (Controls unexposed NOS) (Mixed indications), 2014Kilic (Phenytoin) (Controls unexposed, sick) (Mixed indications), 2014Artama (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013Artama (Phenytoin) (Controls unexposed, disease free), 2013Artama (Phenytoin) (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.
S9275 R32160	Kilic (Phenytoin) (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	4.31 [0.47;39.33] C excluded (control group)	1/5   48/876	49	5		ref
S9276 R32163	Kilic (Phenytoin) (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	6.92 [0.77;61.90] C excluded (control group)	1/5   23,503/673,844	23,504	5		ref
S9277 R32166	Kilic (Phenytoin) (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	5.05 [0.56;45.32] C	1/5   249/5,275	250	5		ref
S9187 R31778	Artama (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.11 [0.13;9.64] C excluded (control group)	1/26   6/173	7	26		ref
S9188 R31790	Artama (Phenytoin) (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	1.33 [0.18;9.92] excluded (control group)	1/26   21,546/719,509	21,547	26		ref
S9190 R31814	Artama (Phenytoin) (Controls unexposed, sick), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes	0.99 [0.13;7.66]	1/26   65/1,793	66	26		ref
					Total	2 studies	2.12 [0.43;10.42]		316	31
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 9187, 9188, 9275, 9276