Ondansetron

Congenital heart defects

id	Study   Auto Huybrechts, 2019Zambelli-Weiner (Unexposed control, NOS), 2019Zambelli-Weiner (Unexposed control, sick), 2019Huybrechts (Control exposed to other treatment), 2018Huybrechts (Unexposed control), 2018Fejzo (Mainly exposed to other treatements, sick), 2016Fejzo (Unexposed control, disease free), 2016Danielsson, 2014Andersen, 2013	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.
S3852 R8207	Huybrechts, 2019	Cardiac malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Intravenous	0.97 [0.86;1.10]	-/23,866   -/1,762,018	-	23,866		ref
S2757 R3713	Zambelli-Weiner (Unexposed control, NOS), 2019	Cardiac Defects	1st trimester	nested case control	unexposed (general population or NOS) excluded	Adjustment: Yes	1.43 [1.28;1.61] excluded (control group)	303/1,181   29,001/142,107	29,304	1,181		ref
S3041 R4609	Zambelli-Weiner (Unexposed control, sick), 2019	Cardiac defects	1st trimester	nested case control	unexposed, sick	Adjustment: Yes	1.48 [1.14;1.92]	303/-   29,001/-	29,304	-		ref
S2852 R3860	Huybrechts (Control exposed to other treatment), 2018	Cardiac malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: Yes	1.01 [0.92;1.12] excluded (control group)	518/55,579   1,628/185,699	2,146	55,579		ref
S2844 R3814	Huybrechts (Unexposed control), 2018	Cardiac malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes	0.99 [0.93;1.06]	835/88,446   14,573/1,727,546	15,408	88,446		ref
S2778 R3783	Fejzo (Mainly exposed to other treatements, sick), 2016	Heart Defect	1st trimester	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No	5.12 [0.28;92.79] C excluded (control group)	5/952   0/441	5	952		ref
S2776 R3745	Fejzo (Unexposed control, disease free), 2016	Heart defects	1st trimester	retrospective cohort	unexposed, disease free	Adjustment: No	0.84 [0.28;2.59] C	5/952   8/1,286	13	952		ref
S2752 R3661	Danielsson, 2014	Cardiovascular defect	early pregnancy	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	1.62 [1.04;2.54]	19/1,349   14,872/1,501,434	14,891	1,349		ref
S2753 R3672	Andersen, 2013	Heart defects	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	2.00 [0.30;3.10]	-/1,248   -/895,770	-	1,248		ref
					Total	6 studies	1.13 [0.96;1.33]		59,616	115,861
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 2778, 2852, 2757