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

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

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.
S17614
R74401		 Araujo - Sertaconazole (Topical), 2022 Major congenital anomalies overall 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Route of exposure Azoles: Dermal/Topical 1.01 [0.84;1.21] -/-   -/91,976 - -
ref
S10366
R38030		 Zhu - Azoles (Local routes), 2020 Any congenital malformation 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Route of exposure Azoles: Local (NOS) 1.05 [1.01;1.10] C 2,840/82,090   61,633/1,875,257 64,473 82,090
ref
S4170
R38187		 Rotem - Clotrimazole (Vaginal), 2018 Major malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Route of exposure Azoles: Vaginal 1.11 [0.93;1.33] 134/1,993   5,777/95,781 5,911 1,993
ref
S17524
R73737		 Czeizel - Clotrimazole, 1999 Congenital abnormalities (excluding infants with three mild defects (congenital dislocation of hip based on Ortolani click, congenital inguinal hernia, and hemangiomas), syndromes of known origin (eg, chromosome disorders), and minor anomalies) 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Matched Route of exposure Azoles: Local (NOS) 0.95 [0.79;1.14] 253/751   18,262/50,568 18,515 751
ref
S4260
R38179		 Jick - Azole (Topical route), 1999 Congenital anomaly 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Route of exposure Azoles: Local (NOS) 0.60 [0.20;1.60] 5/492   26/1,629 31 492
ref
S4370
R10283		 Rosa - Clotrimazole, 1987 Birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Route of exposure Azoles: Local (NOS) 1.09 [0.90;1.40] 74/1,086   6,490/103,253 6,564 1,086
ref
Total 6 studies 1.05 [1.01;1.09] 95,494 86,412
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 Araujo - Sertaconazole (Topical), 2022Araujo - Sertaconazole, 2022 1 1.01[0.84; 1.21]--4%ROB confusion: unclearROB selection: lowROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Zhu - Azoles (Local routes), 2020Zhu - Azoles, 2020 2 1.05[1.01; 1.10]64,47382,09086%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Rotem - Clotrimazole (Vaginal), 2018Rotem - Clotrimazole, 2018 3 1.11[0.93; 1.33]5,9111,9934%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Czeizel - Clotrimazole, 1999Czeizel - Clotrimazole, 1999 0.95[0.79; 1.14]18,5157514%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Jick - Azole (Topical route), 1999Jick - Azole, 1999 4 0.60[0.20; 1.60]314920%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Rosa - Clotrimazole, 1987Rosa - Clotrimazole, 1987 1.09[0.90; 1.40]6,5641,0863%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Total (6 studies) I2 = 0% 1.05[1.01; 1.09]95,49486,4120.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Topical; 2: Local routes; 3: Vaginal; 4: Topical route;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.05[1.02; 1.09]70,41584,5750%NAAraujo - Sertaconazole (Topical), 2022 Zhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Jick - Azole (Topical route), 1999 4 case control studiescase control studies 1.00[0.87; 1.16]25,0791,8370%NACzeizel - Clotrimazole, 1999 Rosa - Clotrimazole, 1987 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.05[1.01; 1.09]95,49486,4120%NAAraujo - Sertaconazole (Topical), 2022 Zhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 Rosa - Clotrimazole, 1987 6 Tags Adjustment   - No  - No 1.05[1.02; 1.10]71,06883,6680%NAZhu - Azoles (Local routes), 2020 Jick - Azole (Topical route), 1999 Rosa - Clotrimazole, 1987 3   - Yes  - Yes 1.02[0.92; 1.14]24,4262,7440%NAAraujo - Sertaconazole (Topical), 2022 Rotem - Clotrimazole (Vaginal), 2018 Czeizel - Clotrimazole, 1999 3 MatchedMatched 0.95[0.79; 1.14]18,515751 -NACzeizel - Clotrimazole, 1999 1 Route of exposure Azoles   - Dermal/Topical  - Dermal/Topical 1.01[0.84; 1.21]-- -NAAraujo - Sertaconazole (Topical), 2022 1   - Local (NOS)  - Local (NOS) 1.05[1.01; 1.09]89,58384,4190%NAZhu - Azoles (Local routes), 2020 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 Rosa - Clotrimazole, 1987 4   - Vaginal  - Vaginal 1.11[0.93; 1.33]5,9111,993 -NARotem - Clotrimazole (Vaginal), 2018 1 All studiesAll studies 1.05[1.01; 1.09]95,49486,4120%NAAraujo - Sertaconazole (Topical), 2022 Zhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 Rosa - Clotrimazole, 1987 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.21.30.6370.000Araujo - Sertaconazole (Topical), 2022Zhu - Azoles (Local routes), 2020Rotem - Clotrimazole (Vaginal), 2018Czeizel - Clotrimazole, 1999Jick - Azole (Topical route), 1999Rosa - Clotrimazole, 1987

Asymetry test p-value = 0.3265 (by Egger's regression)

slope=0.0645 (0.0189); intercept=-0.4775 (0.4274); t=1.1172; p=0.3265

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) 1.05[1.01; 1.09]95,49486,4120%NAAraujo - Sertaconazole (Topical), 2022 Zhu - Azoles (Local routes), 2020 Rotem - Clotrimazole (Vaginal), 2018 Czeizel - Clotrimazole, 1999 Jick - Azole (Topical route), 1999 Rosa - Clotrimazole, 1987 60.510.01.0