Phenobarbital (Epilepsy)

Minor congenital malformations

id	Study   Auto Barroso (Phenobarbital), 2015Dean (Phenobarbital), 2002Battino (Phenobarbital), 1992Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991Robert (Phenobarbital), 1986	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.
S6723 R19004	Barroso (Phenobarbital), 2015	Minor anomalies	during pregnancy (anytime or not specified) excluded	retrospective cohort	unexposed, disease free	Adjustment: No	2.01 [0.23;17.72] C excluded (exposition period)	1/32   5/316	6	32		ref
S6678 R18481	Dean (Phenobarbital), 2002	Minor congenital malformations	at least 1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	3.99 [1.37;11.69] C	23/61   5/38	28	61		ref
S7272 R21041	Battino (Phenobarbital), 1992	Minor anomalies	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.43 [0.13;46.54] C	7/60   0/9	7	60		ref
S5526 R19261	Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991	Waldrop score >2	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	4.50 [1.20;16.89] C excluded (control group)	6/12   10/55	16	12		ref
S6824 R19311	Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	Waldrop score >2	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	1.20 [0.29;4.91] C	6/12   10/22	16	12		ref
S5514 R16206	Robert (Phenobarbital), 1986	Minor malformations	1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	0.86 [0.20;3.73] C	4/40   4/35	8	40		ref
					Total	4 studies	1.92 [0.88;4.18]		59	173
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 5526