TNF-alpha inhibitors

Low birth weight (< 2500g)

id	Study   Auto Duricova, 2019Chaparro, 2018De Lima, 2018Carman - Etanercept (Controls unexposed, disease free), 2017Carman - Etanercept (Controls unexposed, sick), 2017Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017De Lima (Controls unexposed, disease free), 2016De Lima (Treatment stopped during pregnancy, sick), 2016Komoto, 2016Weber-Schoendorfer, 2015Seirafi, 2014Schnitzler (Controls unexposed, disease free), 2011Schnitzler (Unexposed control, sick), 2011	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.
S3072 R4704	Duricova, 2019	Low birth weight (weight < 2500g)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free	Adjustment: No	2.96 [0.30;29.13] C	3/72   1/69	4	72		ref
S3066 R4669	Chaparro, 2018	Low birth weight (<2,500 mg)	3 months (or more) before pregnancy or during pregnancy excluded	retrospective cohort	unexposed, sick	Adjustment: No	1.61 [0.99;2.62] C excluded (exposition period)	41/388   31/453	72	388		ref
S3123 R4857	De Lima, 2018	Low birth weight (NOS)	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	0.79 [0.01;43.11] C	0/15   0/12	0	15		ref
S4098 R8759	Carman - Etanercept (Controls unexposed, disease free), 2017	Birth weight <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, disease free excluded	Adjustment: No	2.20 [1.41;3.44] C excluded (control group)	31/217   76/1,081	107	217		ref
S4099 R8774	Carman - Etanercept (Controls unexposed, sick), 2017	Birth weight <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed, sick	Adjustment: No	1.71 [1.14;2.58] C	31/217   172/1,940	203	217		ref
S4106 R8799	Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017	Birth weight (≤10th centile)	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.73 [0.33;1.62]	-/-   -/-	-	-		ref
S3070 R4686	De Lima (Controls unexposed, disease free), 2016	Low birth weight (birth weight lower than 2500 g)	1st and 2nd trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No	2.85 [1.26;6.46] C excluded (control group)	8/83   29/804	37	83		ref
S3071 R4695	De Lima (Treatment stopped during pregnancy, sick), 2016	Low birth weight (birth weight lower than 2500 g)	1st and 2nd trimester	prospective cohort	unexposed, sick	Adjustment: No	0.95 [0.21;4.29] C	3/32   5/51	8	32		ref
S13735 R53499	Komoto, 2016	Low birth weight (<2500G)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No	0.97 [0.24;3.95] C	4/17   7/29	11	17		ref
S2888 R4119	Weber-Schoendorfer, 2015	Low birth weight (<2500 g)	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	13.45 [7.36;24.59] C	51/399   14/1,299	65	399		ref
S3037 R4571	Seirafi, 2014	Low birth weight (< 2500 g)	3 months (or more) before pregnancy or during pregnancy excluded	retrospective cohort	unexposed, sick	Adjustment: No before conception and/or during pregnancy	1.73 [0.74;4.02] C excluded (exposition period)	19/118   9/90	28	118		ref
S3017 R4515	Schnitzler (Controls unexposed, disease free), 2011	Low birth weight (<2500g)	3 months (or more) before pregnancy or during pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No before conception and/or during pregnancy	1.98 [0.55;7.16] C excluded (control group)	6/32   5/48	11	32		ref
S3018 R4520	Schnitzler (Unexposed control, sick), 2011	Low birth weight (<2500g)	3 months (or more) before pregnancy or during pregnancy excluded	prospective cohort	unexposed, sick	Adjustment: No before conception and/or during pregnancy	1.44 [0.46;4.46] C excluded (exposition period)	6/32   9/65	15	32		ref
					Total	7 studies	1.86 [0.66;5.25]		291	752
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 3017, 3070, 4098