Azoles (local routes 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.
S10366
R38031		 Zhu - Azoles (Local routes), 2020 Cardiovascular malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Route of exposure Azoles: Local (NOS) 1.07 [1.00;1.16] C 761/82,090   16,192/1,875,257 16,953 82,090
ref
S4170
R9629		 Rotem - Clotrimazole (Vaginal), 2018 Cardiovascular system 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Route of exposure Azoles: Vaginal 0.92 [0.68;1.24] 46/1,993   2,398/95,781 2,444 1,993
ref
S17545
R73873		 Carter - Clotrimazole, 2008 Cardiovascular defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Route of exposure Azoles: Local (NOS) 1.12 [0.35;3.53] C 5/12   3,044/7,811 3,049 12
ref
S17524
R73720		 Czeizel - Clotrimazole, 1999 Cardiovascular congenital anomalies 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Matched Route of exposure Azoles: Local (NOS) 0.95 [0.60;1.49] 39/537   3,433/35,739 3,472 537
ref
S4260
R9866		 Jick - Azole (Topical route), 1999 Heart defect 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Route of exposure Azoles: Local (NOS) 0.30 [0.02;5.44] C 0/492   5/1,629 5 492
ref
Total 5 studies 1.06 [0.99;1.14] 25,923 85,124
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 - Azoles (Local routes), 2020Zhu - Azoles, 2020 1 1.07[1.00; 1.16]16,95382,09092%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Rotem - Clotrimazole (Vaginal), 2018Rotem - Clotrimazole, 2018 2 0.92[0.68; 1.24]2,4441,9935%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Carter - Clotrimazole, 2008Carter - Clotrimazole, 2008 1.12[0.35; 3.53]3,049120%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Czeizel - Clotrimazole, 1999Czeizel - Clotrimazole, 1999 0.95[0.60; 1.49]3,4725372%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Jick - Azole (Topical route), 1999Jick - Azole, 1999 3 0.30[0.02; 5.44]54920%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 0% 1.06[0.99; 1.14]25,92385,1240.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Local routes; 2: Vaginal; 3: Topical route;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.06[0.99; 1.14]19,40284,5750%NAZhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Jick - Azole (Topical route), 1999 3 case control studiescase control studies 0.97[0.64; 1.48]6,5215490%NACarter - Clotrimazole, 2008 Czeizel - Clotrimazole, 1999 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.06[0.99; 1.14]25,92385,1240%NAZhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Carter - Clotrimazole, 2008 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 5 Tags Adjustment   - No  - No 1.07[1.00; 1.15]20,00782,5940%NAZhu - Azoles (Local routes), 2020 Carter - Clotrimazole, 2008 Jick - Azole (Topical route), 1999 3   - Yes  - Yes 0.93[0.72; 1.19]5,9162,5300%NARotem - Clotrimazole (Vaginal), 2018 Czeizel - Clotrimazole, 1999 2 MatchedMatched 0.95[0.60; 1.50]3,472537 -NACzeizel - Clotrimazole, 1999 1 Route of exposure Azoles   - Local (NOS)  - Local (NOS) 1.07[1.00; 1.15]23,47983,1310%NAZhu - Azoles (Local routes), 2020 Carter - Clotrimazole, 2008 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 4   - Vaginal  - Vaginal 0.92[0.68; 1.24]2,4441,993 -NARotem - Clotrimazole (Vaginal), 2018 1 All studiesAll studies 1.06[0.99; 1.14]25,92385,1240%NAZhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Carter - Clotrimazole, 2008 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 50.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.51.7740.000Zhu - Azoles (Local routes), 2020Rotem - Clotrimazole (Vaginal), 2018Carter - Clotrimazole, 2008Czeizel - Clotrimazole, 1999Jick - Azole (Topical route), 1999

Asymetry test p-value = 0.1232 (by Egger's regression)

slope=0.0919 (0.0236); intercept=-0.6287 (0.2954); t=2.1281; p=0.1232

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) 1.06[0.99; 1.14]25,92385,1240%NAZhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Carter - Clotrimazole, 2008 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 50.510.01.0