Phenobarbital (All indications)

Hypospadias

id	Study   Auto Blotière (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019Blotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019Tomson (Phenobarbital), 2018Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Phenobarbital), 2011D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991D'Souza (Phenobarbital) (Controls unexposed, sick), 1991Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	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.
S10172 R37171	Blotière (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019	Hypospadias	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	2.51 [0.14;44.28] C excluded (control group)	0/80   7/2,997	7	80		ref
S10042 R36307	Blotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019	Hypospadias	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	3.49 [0.22;56.34] C	0/80   3,371/1,875,733	3,371	80		ref
S9151 R31458	Tomson (Phenobarbital), 2018	Hypospadias	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.43 [0.17;11.89] C	1/294   6/2,514	7	294		ref
S9107 R31282	Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012	Hypospadias	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No Controls: mixed indications	23.72 [0.96;584.27] C	1/199   0/1,562	1	199		ref
S9124 R31347	Bànhidy (Phenobarbital), 2011	Hypospadias	throughout pregnancy	case control	unexposed, sick	Adjustment: No Matched	3.80 [0.06;243.53] C	0/   3/13	3	0		ref
S9101 R31185	D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991	Hypospadias	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	17.57 [0.30;1024.08] C excluded (control group)	0/4   0/62	0	4		ref
S9102 R31214	D'Souza (Phenobarbital) (Controls unexposed, sick), 1991	Hypospadias	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	2.14 [0.03;131.94] C	0/4   0/8	0	4		ref
S9172 R31576	Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991	Hypospadias	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	4.74 [0.09;251.42] C excluded (control group)	0/12   0/55	0	12		ref
S9173 R31601	Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	Hypospadias	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	1.87 [0.03;100.54] C	0/12   0/22	0	12		ref
					Total	6 studies	3.10 [0.88;10.93]		3,382	589
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 9101, 9172, 10172