Infliximab

All congenital malformations (majors, minors, majors and minors, or unspecified)

id	Study   Auto De Lorenzo (Controls unexposed, disease free), 2020De Lorenzo (Controls unexposed, sick), 2020Bröms (controls unexposed, disease free), 2016Bröms (controls unexposed, sick), 2016Weber-Schoendorfer, 2015Seirafi, 2014Casanova, 2013Schnitzler (Unexposed control, disease free), 2011Schnitzler (Unexposed control, sick), 2011Hyrich, 2006	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.
S4966 R13041	De Lorenzo (Controls unexposed, disease free), 2020	Malformations	at least 1st trimester	retrospective cohort	unexposed, disease free excluded	Adjustment: No	4.60 [0.15;144.69] C excluded (control group)	0/3   1/36	1	3		ref
S4967 R13047	De Lorenzo (Controls unexposed, sick), 2020	Malformations	at least 1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	12.60 [0.20;780.42] C	0/3   0/32	0	3		ref
S4077 R11362	Bröms (controls unexposed, disease free), 2016	Any major birth defect	3 months or more before pregnancy or1st trimester	population based cohort retrospective	unexposed, disease free excluded	Adjustment: No	1.39 [0.71;2.73] C excluded (control group)	9/156   52,592/1,250,192	52,601	156		ref
S4078 R11363	Bröms (controls unexposed, sick), 2016	Any major birth defect	3 months or more before pregnancy or1st trimester excluded	population based cohort retrospective	unexposed, sick	Adjustment: Yes	1.31 [0.62;2.45] excluded (exposition period)	9/156   1,019/21,549	1,028	156		ref
S2912 R11369	Weber-Schoendorfer, 2015	Major birth defects	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	3.05 [1.28;7.30] C	7/156   21/1,385	28	156		ref
S3089 R11364	Casanova, 2013	Congenital malformations (NOS)	3 months (or more) before pregnancy or during pregnancy excluded	retrospective cohort	exposed to other treatment, sick	Adjustment: No	5.41 [0.21;137.20] C excluded (exposition period)	0/20   1/318	1	20		ref
S3019 R4529	Schnitzler (Unexposed control, disease free), 2011	Malformations (NOS)	3 months (or more) before pregnancy or during pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No	1.61 [0.03;82.96] C excluded (control group)	0/35   0/56	0	35		ref
S3020 R4530	Schnitzler (Unexposed control, sick), 2011	Malformations (NOS)	3 months (or more) before pregnancy or during pregnancy excluded	prospective cohort	unexposed, sick	Adjustment: No	0.74 [0.03;18.61] C excluded (exposition period)	0/35   1/78	1	35		ref
S5000 R15982	Hyrich, 2006	Major fetal abnormalities	1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	5.00 [0.07;366.35] C	0/2   0/8	0	2		ref
					Total	3 studies	3.30 [1.43;7.61]		28	161
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 3019, 4077, 4966