Antimycotic Azoles (all routes except local only) updated on 01-29-2025

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.
S17739
R74981		 Zhu - Fluconazole, 2020 Cardiovascular malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose 1.03 [0.93;1.13] 396/37,648   19,174/1,872,961 19,570 37,648
ref
S17735
R74926		 Molgaard-Nielsen - Fluconazole, 2013 Any heart defects 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose 1.20 [0.95;1.50] 76/7,352   7,835/968,236 7,911 7,352
ref
S17725
R74800		 Carter - Miconazole, 2008 Cardiovascular defects 1st trimester case control unexposed (general population or NOS) Adjustment: No 0.52 [0.28;0.98] C 13/52   3,036/7,771 3,049 52
ref
S17728
R74811		 Kazy - Ketoconazole, 2005 Cardiovascular congenital anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes 3.10 [0.60;15.60] 2/8   4,477/42,622 4,479 8
ref
S17745
R75033		 Jick - Fluconazole and Itraconazole (Oral), 1999 Heart defect 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 2.03 [0.39;10.51] C 2/322   5/1,629 7 322
ref
Total 5 studies 1.04 [0.81;1.34] 35,016 45,382
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 Zhu - Fluconazole, 2020Zhu - Fluconazole, 2020 1.03[0.93; 1.13]19,57037,64848%ROB confusion: lowROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Molgaard-Nielsen - Fluconazole, 2013Molgaard-Nielsen - Fluconazole, 2013 1.20[0.95; 1.50]7,9117,35236%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Carter - Miconazole, 2008Carter - Miconazole, 2008 0.52[0.28; 0.98]3,0495212%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Kazy - Ketoconazole, 2005Kazy - Ketoconazole, 2005 3.10[0.60; 15.60]4,47982%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Jick - Fluconazole and Itraconazole (Oral), 1999Jick - Fluconazole and Itraco..., 1999 1 2.03[0.39; 10.51]73222%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 53% 1.04[0.81; 1.34]35,01645,3820.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Oral;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.06[0.96; 1.17]27,48845,3223%NAZhu - Fluconazole, 2020 Molgaard-Nielsen - Fluconazole, 2013 Jick - Fluconazole and Itraconazole (Oral), 1999 3 case control studiescase control studies 1.08[0.19; 6.01]7,5286075%NACarter - Miconazole, 2008 Kazy - Ketoconazole, 2005 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.04[0.81; 1.34]35,01645,38253%NAZhu - Fluconazole, 2020 Molgaard-Nielsen - Fluconazole, 2013 Carter - Miconazole, 2008 Kazy - Ketoconazole, 2005 Jick - Fluconazole and Itraconazole (Oral), 1999 5 Tags Adjustment   - No  - No 0.82[0.23; 2.91]3,05637457%NACarter - Miconazole, 2008 Jick - Fluconazole and Itraconazole (Oral), 1999 2   - Yes  - Yes 1.10[0.93; 1.30]31,96045,00836%NAZhu - Fluconazole, 2020 Molgaard-Nielsen - Fluconazole, 2013 Kazy - Ketoconazole, 2005 3 Fluconazole not specified or mixed doseFluconazole not specified or mixed dose 1.07[0.94; 1.22]27,48145,00031%NAZhu - Fluconazole, 2020 Molgaard-Nielsen - Fluconazole, 2013 2 All studiesAll studies 1.04[0.81; 1.34]35,01645,38253%NAZhu - Fluconazole, 2020 Molgaard-Nielsen - Fluconazole, 2013 Carter - Miconazole, 2008 Kazy - Ketoconazole, 2005 Jick - Fluconazole and Itraconazole (Oral), 1999 50.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.02.01.0070.000Zhu - Fluconazole, 2020Molgaard-Nielsen - Fluconazole, 2013Carter - Miconazole, 2008Kazy - Ketoconazole, 2005Jick - Fluconazole and Itraconazole (Oral), 1999

Asymetry test p-value = 0.7815 (by Egger's regression)

slope=0.0224 (0.1038); intercept=0.3119 (1.0286); t=0.3032; p=0.7815

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.81; 1.34]35,01645,38253%NAZhu - Fluconazole, 2020 Molgaard-Nielsen - Fluconazole, 2013 Carter - Miconazole, 2008 Kazy - Ketoconazole, 2005 Jick - Fluconazole and Itraconazole (Oral), 1999 50.510.01.0