Glucagon-like peptide-1 (GLP-1) receptor agonists

Congenital heart defects

id	Study   Auto Lewin, 2025Cesta_Israel, 2024Cesta_Nordic, 2024Cesta_USA, 2024	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 trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	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.
S18829 R80176	Lewin, 2025	Cardiac malformations	during pregnancy (anytime or not specified) excluded	retrospective cohort (claims database)	unexposed, sick	Adjustment: No GLP1-RA indication: Type 2 diabetes (T2D)	1.02 [0.92;1.13] C excluded (exposition period)	509/40,929   1,597/131,279	2,106	40,929		ref
S18787 R79958	Cesta_Israel, 2024	Cardiac malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick	Adjustment: No GLP1-RA indication: Type 2 diabetes (T2D)	0.82 [0.05;14.36] C	0/20   13/447	13	20		ref
S18785 R79950	Cesta_Nordic, 2024	Cardiac malformations	1st trimester	population based cohort retrospective	exposed to other treatment, sick	Adjustment: No GLP1-RA indication: Type 2 diabetes (T2D)	0.39 [0.10;1.56]	-/110   147/3,164	-	110		ref
S18786 R79954	Cesta_USA, 2024	Cardiac malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick	Adjustment: No GLP1-RA indication: Type 2 diabetes (T2D)	0.49 [0.21;1.14]	6/331   58/1,583	64	331		ref
					Total	3 studies	0.48 [0.24;0.96]		77	461
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

Umbrella review (other published meta-analyses)