Ondansetron

Congenital heart defects

R analysis
id Study   Lib. in paper Exposition period    Study type  Control type 
 
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] 303/294   29,001/29,001 29,304 294
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] 59,616 116,155
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

StudyTE95% CIn casesn exposedweightROBABCDEF Huybrechts, 2019Huybrechts, 2019 0.97[0.86; 1.10]-23,86631%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zambelli-Weiner (Unexposed control, sick), 2019Zambelli-Weiner, 2019 1 1.48[1.14; 1.92]29,30429419%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Huybrechts (Unexposed control), 2018Huybrechts, 2018 2 0.99[0.93; 1.06]15,40888,44636%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Fejzo (Unexposed control, disease free), 2016Fejzo, 2016 3 0.84[0.28; 2.59]139522%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Danielsson, 2014Danielsson, 2014 1.62[1.04; 2.54]14,8911,34910%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Andersen, 2013Andersen, 2013 2.00[0.30; 3.10]-1,2482%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 66% 1.13[0.96; 1.33]59,616116,1550.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Unexposed control, sick; 2: Unexposed control; 3: Unexposed control, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.91; 1.14]30,312115,86136%moderateHuybrechts, 2019 Huybrechts (Unexposed control), 2018 Fejzo (Unexposed control, disease free), 2016 Danielsson, 2014 Andersen, 2013 5 case control studiescase control studies 1.48[1.14; 1.92]29,304294 -moderateZambelli-Weiner (Unexposed control, sick), 2019 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.02[0.91; 1.14]30,312115,86136%moderateHuybrechts, 2019 Huybrechts (Unexposed control), 2018 Fejzo (Unexposed control, disease free), 2016 Danielsson, 2014 Andersen, 2013 5 unexposed, sickunexposed, sick 1.48[1.14; 1.92]29,304294 -moderateZambelli-Weiner (Unexposed control, sick), 2019 1 Tags Adjustment   - No  - No 0.84[0.28; 2.59]13952 -moderateFejzo (Unexposed control, disease free), 2016 1   - Yes  - Yes 1.14[0.96; 1.35]59,603115,20373%moderateHuybrechts, 2019 Zambelli-Weiner (Unexposed control, sick), 2019 Huybrechts (Unexposed control), 2018 Danielsson, 2014 Andersen, 2013 5 IntravenousIntravenous 0.97[0.86; 1.10]-23,866 -moderateHuybrechts, 2019 1 All studiesAll studies 1.13[0.96; 1.33]59,616116,15566%moderateHuybrechts, 2019 Zambelli-Weiner (Unexposed control, sick), 2019 Huybrechts (Unexposed control), 2018 Fejzo (Unexposed control, disease free), 2016 Danielsson, 2014 Andersen, 2013 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.41.50.7150.000Huybrechts, 2019Zambelli-Weiner (Unexposed control, sick), 2019Huybrechts (Unexposed control), 2018Fejzo (Unexposed control, disease free), 2016Danielsson, 2014Andersen, 2013

Asymetry test p-value = 0.1557 (by Egger's regression)

slope=-0.0598 (0.0586); intercept=1.4674 (0.8403); t=1.7464; p=0.1557

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2778, 2852, 2757

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.17[0.95; 1.45]59,616117,04286%NAHuybrechts, 2019 Zambelli-Weiner (Unexposed control, NOS), 2019 Huybrechts (Unexposed control), 2018 Fejzo (Unexposed control, disease free), 2016 Danielsson, 2014 Andersen, 2013 6 unexposed, sick controlsunexposed, sick controls 1.48[1.14; 1.92]29,304294 -NAZambelli-Weiner (Unexposed control, sick), 2019 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.16[0.48; 2.83]2,15156,53117%NAHuybrechts (Control exposed to other treatment), 2018 Fejzo (Mainly exposed to other treatements, sick), 2016 20.510.01.0