Triptans

Major congenital malformations

id	Study   Auto Spielmann (Control mainly exposed other treatments, sick), 2017Spielmann (Control unexposed, disease free), 2017Nezvalová-Henriksen (Control unexposed, disease free), 2013Nezvalová-Henriksen (Control unexposed, sick), 2013Bérard, 2012Källén (control exposed to ergots), 2011Källén (control unexposed, disease free), 2011Shuhaiber - Sumatriptan (Control exposed to other treatments), 1998Shuhaiber - Sumatriptan (Control unexposed, disease free), 1998	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 specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S3510 R6888	Spielmann (Control mainly exposed other treatments, sick), 2017	Major birth defects	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.88 [0.36;2.18] C excluded (control group)	8/323   12/429	20	323		ref
S3509 R6864	Spielmann (Control unexposed, disease free), 2017	Major birth defects	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	0.86 [0.40;1.83] C	8/323   44/1,526	52	323		ref
S3492 R6764	Nezvalová-Henriksen (Control unexposed, disease free), 2013	Congenital malformations (major)	1st trimester	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.14 [0.84;1.55] excluded (control group)	43/1,210   5,292/178,565	5,335	1,210		ref
S851 R6746	Nezvalová-Henriksen (Control unexposed, sick), 2013	Congenital malformations (major)	1st trimester	population based cohort retrospective	unexposed, sick	Adjustment: No	0.77 [0.51;1.17] C	43/1,210   50/1,095	93	1,210		ref
S850 R6554	Bérard, 2012	Major congenital malformations	during pregnancy (anytime or not specified) excluded	nested case control	unexposed, disease free	Adjustment: Yes	1.49 [0.89;2.52] excluded (exposition period)	18/139   4,698/59,568	4,716	139		ref
S3494 R6811	Källén (control exposed to ergots), 2011	Relatively severe malformations	1st trimester	population based cohort propective	exposed to other treatment, sick excluded	Adjustment: No	1.03 [0.61;1.74] C excluded (control group)	92/2,777   17/527	109	2,777		ref
S849 R6543	Källén (control unexposed, disease free), 2011	Relatively severe malformations	1st trimester	population based cohort propective	unexposed, disease free	Adjustment: Yes	1.04 [0.84;1.28]	92/2,777   38,818/1,229,901	38,910	2,777		ref
S3595 R7303	Shuhaiber - Sumatriptan (Control exposed to other treatments), 1998	Major congenital malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.10 [0.07;17.86] C excluded (control group)	1/82   1/90	2	82		ref
S3596 R7307	Shuhaiber - Sumatriptan (Control unexposed, disease free), 1998	Major congenital malformations	at least 1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	1.11 [0.07;18.06] C	1/82   1/91	2	82		ref
					Total	4 studies	0.97 [0.81;1.17]		39,057	4,392
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 3595, 3494, 3492, 3510