Ondansetron

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

id	Study   Auto Bérard, 2019Huybrechts, 2019Huybrechts (Control exposed to other treatment), 2018Huybrechts (Unexposed control), 2018Fejzo (Mainly exposed to other treatements, sick), 2016Fejzo (Unexposed control, disease free), 2016Shahraki, 2016Danielsson, 2014Ozdemirci, 2014Andersen, 2013Colvin, 2013Einarson (Control exposed to other antiemetics), 2004Einarson (Unexposed control), 2004	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.
S3471 R11257	Bérard, 2019	Major malformations	1st trimester	population based cohort propective	unexposed (general population or NOS)	Adjustment: Yes	0.57 [0.13;2.49]	2/31   14,402/179,106	14,404	31		ref
S3852 R11260	Huybrechts, 2019	Congenital malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Intravenous	1.02 [0.96;1.08]	-/23,866   -/1,762,018	-	23,866		ref
S2852 R11261	Huybrechts (Control exposed to other treatment), 2018	Any congenital malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: Yes	1.00 [0.95;1.05] excluded (control group)	2,067/55,579   6,137/185,699	8,204	55,579		ref
S2844 R11262	Huybrechts (Unexposed control), 2018	Any congenital malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes	1.01 [0.98;1.05]	3,275/88,446   54,163/1,727,546	57,438	88,446		ref
S2778 R3782	Fejzo (Mainly exposed to other treatements, sick), 2016	Birth Defects (major and minor)	1st trimester	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.02 [0.55;1.90] C excluded (control group)	33/952   15/441	48	952		ref
S2776 R3744	Fejzo (Unexposed control, disease free), 2016	Birth Defects (major and minor)	1st trimester	retrospective cohort	unexposed, disease free	Adjustment: No	1.89 [1.11;3.22] C	33/952   24/1,286	57	952		ref
S2856 R3995	Shahraki, 2016	Congenital anomaly	during pregnancy (anytime or not specified) excluded	randomized controlled trial	exposed to other treatment, sick	Adjustment: Randomisation	1.14 [0.02;57.92] C excluded (exposition period)	0/88   0/100	0	88		ref
S2752 R3659	Danielsson, 2014	Any malformation	early pregnancy	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	0.95 [0.72;1.26]	49/1,349   64,215/1,501,434	64,264	1,349		ref
S3184 R5102	Ozdemirci, 2014	Fetal anomaly	1st trimester	retrospective cohort	exposed to other treatment, sick	Adjustment: No	0.20 [0.02;1.87] C	1/100   4/85	5	100		ref
S2753 R11255	Andersen, 2013	Major congenital malformations	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	1.30 [1.00;1.70]	58/1,248   31,357/895,770	31,415	1,248		ref
S2775 R3722	Colvin, 2013	Any birth defect	during pregnancy (anytime or not specified) excluded	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	1.30 [0.80;2.10] excluded (exposition period)	16/263   4,749/98,062	4,765	263		ref
S2755 R11258	Einarson (Control exposed to other antiemetics), 2004	Major malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.93 [0.47;7.84] C excluded (control group)	6/169   3/160	9	169		ref
S2754 R11259	Einarson (Unexposed control), 2004	Major malformations	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	1.95 [0.48;7.94] C	6/169   3/162	9	169		ref
					Total	8 studies	1.04 [0.96;1.12]		167,592	116,161
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 2755, 2778, 2852