Phenytoin (All indications)

Preterm (< 37 weeks)

id	Study   Auto Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020Aydin (Phenytoin) (Controls unexposed, sick), 2020Bank (Phenytoin) (Mixed indications), 2017Arkilo (Phenytoin), 2015Kilic (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), 2013Pennell (Phenytoin), 2012Koch (Phenytoin), 1996	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.
S9192 R31819	Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020	Preterm delivery (before 37 weeks of gestation)	throughout pregnancy	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No	13.00 [0.10;1680.94] C excluded (control group)	0/1   0/7	0	1		ref
S9193 R31829	Aydin (Phenytoin) (Controls unexposed, sick), 2020	Preterm delivery (before 37 weeks of gestation)	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No	7.80 [0.12;487.53] C	0/1   2/22	2	1		ref
S9272 R32150	Bank (Phenytoin) (Mixed indications), 2017	Premature (<37 weeks gestation)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick	Adjustment: No	4.60 [0.15;144.69] C	0/3   1/36	1	3		ref
S9186 R31764	Arkilo (Phenytoin), 2015	Premature delivery	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick	Adjustment: No	0.65 [0.03;14.95] C	0/5   3/24	3	5		ref
S9275 R32162	Kilic (Phenytoin) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.06 [0.06;19.86] C excluded (control group)	0/5   83/880	83	5		ref
S9276 R32165	Kilic (Phenytoin) (Controls unexposed NOS) (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: No	2.10 [0.11;39.05] C excluded (control group)	0/5   33,974/676,834	33,974	5		ref
S9277 R32168	Kilic (Phenytoin) (Controls unexposed, sick) (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: No Controls: epilepsy indication	1.42 [0.08;26.49] C	0/5   383/5,296	383	5		ref
S9187 R31777	Artama (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013	Preterm birth (<37 gestational weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.72 [0.34;8.58] C excluded (control group)	2/26   8/173	10	26		ref
S9188 R31789	Artama (Phenytoin) (Controls unexposed, disease free), 2013	Preterm birth (<37 gestational weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.85 [0.43;7.88] excluded (control group)	2/26   30,027/719,509	30,029	26		ref
S9190 R31813	Artama (Phenytoin) (Controls unexposed, sick), 2013	Preterm birth (<37 gestational weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes	1.52 [0.34;6.76]	2/26   85/1,793	87	26		ref
S9216 R31976	Pennell (Phenytoin), 2012	Preterm Birth (< 37 weeks GA)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.88 [0.57;6.13] C	6/55   6/98	12	55		ref
S9263 R32124	Koch (Phenytoin), 1996	Prematurity (< 37 weeks)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched	11.64 [0.97;139.55] C	2/13   1/65	3	13		ref
					Total	7 studies	2.14 [0.99;4.62]		491	108
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, 9192