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

Late intrauterine deaths (> 22 weeks)

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.
S17833
R75258		 Berard - Fluconazole, 2019 Stillbirth (fetal deaths with a birth weight of ≥ 500 g or ≥ 20 weeks of gestation) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose Matched 0.56 [0.12;2.64] 3/44   709/7,788 712 44
ref
S17742
R75021		 Pasternak - Fluconazole, 2018 Stillbirth (fetal loss after 22 or 28 completed weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose Matched 0.76 [0.52;1.10] 29/10,669   387/106,690 416 10,669
ref
S17740
R75018		 Molgaard-Nielsen - Fluconazole (Oral) (Controls exposed to pivmecillinam), 2016 Stillbirth (pregnancy loss from 23 weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Fluconazole not specified or mixed dose Matched 2.38 [1.06;5.32]
excluded (control group) 		17/4,357   9/4,357 26 4,357
ref
S17741
R75020		 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 Stillbirth (pregnancy loss from 23 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose Matched 1.32 [0.82;2.14] 21/5,382   77/21,506 98 5,382
ref
S17748
R75066		 De Santis - Itraconazole, 2009 Fetal death 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 3.03 [0.12;74.80] C 1/206   0/207 1 206
ref
S17747
R75053		 Bar-Oz - Itraconazole, 2000 Fetal death 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 1.50 [0.25;9.08] C 3/199   2/198 5 199
ref
S17733
R74842		 Mastroiacovo - Fluconazole, 1996 Stillbirth 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose Matched 0.36 [0.03;3.90] 1/177   3/409 4 177
ref
Total 6 studies 0.93 [0.70;1.23] 1,236 16,677
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 Berard - Fluconazole, 2019Berard - Fluconazole, 2019 0.56[0.12; 2.64]712443%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Pasternak - Fluconazole, 2018Pasternak - Fluconazole, 2018 0.76[0.52; 1.10]41610,66957%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016Molgaard-Nielsen - Fluconazol..., 2016 1 1.32[0.82; 2.14]985,38235%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate De Santis - Itraconazole, 2009De Santis - Itraconazole, 2009 3.03[0.12; 74.80]12061%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bar-Oz - Itraconazole, 2000Bar-Oz - Itraconazole, 2000 1.50[0.25; 9.08]51992%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: criticalROB mesure: criticalROB reporting: moderate Mastroiacovo - Fluconazole, 1996Mastroiacovo - Fluconazole, 1996 0.36[0.03; 3.90]41771%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 0.93[0.70; 1.23]1,23616,6770.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Oral) (Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.97[0.68; 1.37]52416,63312%NAPasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 5 case control studiescase control studies 0.56[0.12; 2.63]71244 -NABerard - Fluconazole, 2019 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.93[0.70; 1.23]1,23616,6770%NABerard - Fluconazole, 2019 Pasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 6 Tags Adjustment   - No  - No 1.78[0.37; 8.53]64050%NADe Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 2   - Yes  - Yes 0.91[0.61; 1.37]1,23016,27227%NABerard - Fluconazole, 2019 Pasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 Mastroiacovo - Fluconazole, 1996 4 Fluconazole not specified or mixed doseFluconazole not specified or mixed dose 0.91[0.61; 1.37]1,23016,27227%NABerard - Fluconazole, 2019 Pasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 Mastroiacovo - Fluconazole, 1996 4 MatchedMatched 0.93[0.70; 1.23]1,23616,6770%NABerard - Fluconazole, 2019 Pasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 6 All studiesAll studies 0.93[0.70; 1.23]1,23616,6770%NABerard - Fluconazole, 2019 Pasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 60.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.81.9630.000Berard - Fluconazole, 2019Pasternak - Fluconazole, 2018Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016De Santis - Itraconazole, 2009Bar-Oz - Itraconazole, 2000Mastroiacovo - Fluconazole, 1996

Asymetry test p-value = 0.8974 (by Egger's regression)

slope=-0.1015 (0.2526); intercept=0.0980 (0.7135); t=0.1374; p=0.8974

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 17740

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.93[0.70; 1.23]1,23616,6770%NABerard - Fluconazole, 2019 Pasternak - Fluconazole, 2018 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.38[1.06; 5.33]264,357 -NAMolgaard-Nielsen - Fluconazole (Oral) (Controls exposed to pivmecillinam), 2016 10.510.01.0