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

Early intrauterine death (< 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
R75257		 Berard - Fluconazole, 2019 Spontaneous abortion (6-20 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 2.67 [2.36;3.03] 594/2,592   28,864/318,276 29,458 2,592
ref
S17740
R75017		 Molgaard-Nielsen - Fluconazole (Oral) (Controls exposed to pivmecillinam), 2016 Spontaneous abortion (before week 22) 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 1.44 [1.14;1.82]
excluded (control group) 		140/3,018   143/3,018 283 3,018
ref
S17741
R75019		 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 Spontaneous abortion (before week 22) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose Matched 1.48 [1.23;1.77] 147/3,315   563/13,246 710 3,315
ref
S17748
R75064		 De Santis - Itraconazole, 2009 Spontaneous abortion 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 2.48 [1.15;5.34] C 23/206   10/207 33 206
ref
S17747
R75051		 Bar-Oz - Itraconazole, 2000 Spontaneous abortion 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 3.25 [1.43;7.40] C 25/199   8/189 33 199
ref
S17733
R74840		 Mastroiacovo - Fluconazole, 1996 Miscarriage 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Fluconazole not specified or mixed dose Matched 1.21 [0.67;2.21] 22/226   34/452 56 226
ref
Total 5 studies 2.01 [1.34;3.00] 30,290 6,538
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 2.67[2.36; 3.03]29,4582,59228%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016Molgaard-Nielsen - Fluconazol..., 2016 1 1.48[1.23; 1.77]7103,31527%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate De Santis - Itraconazole, 2009De Santis - Itraconazole, 2009 2.48[1.15; 5.34]3320614%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bar-Oz - Itraconazole, 2000Bar-Oz - Itraconazole, 2000 3.25[1.43; 7.40]3319913%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: criticalROB mesure: criticalROB reporting: moderate Mastroiacovo - Fluconazole, 1996Mastroiacovo - Fluconazole, 1996 1.21[0.67; 2.21]5622618%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 88% 2.01[1.34; 3.00]30,2906,5380.510.01.0ROB: 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 1.71[1.20; 2.45]8323,94645%NAMolgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 4 case control studiescase control studies 2.67[2.36; 3.03]29,4582,592 -NABerard - Fluconazole, 2019 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.01[1.34; 3.00]30,2906,53888%NABerard - Fluconazole, 2019 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 5 Tags Adjustment   - No  - No 2.81[1.60; 4.93]664050%NADe Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 2   - Yes  - Yes 1.76[1.07; 2.91]30,2246,13394%NABerard - Fluconazole, 2019 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 Mastroiacovo - Fluconazole, 1996 3 Fluconazole not specified or mixed doseFluconazole not specified or mixed dose 1.76[1.07; 2.91]30,2246,13394%NABerard - Fluconazole, 2019 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 Mastroiacovo - Fluconazole, 1996 3 MatchedMatched 2.01[1.34; 3.00]30,2906,53888%NABerard - Fluconazole, 2019 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 5 All studiesAll studies 2.01[1.34; 3.00]30,2906,53888%NABerard - Fluconazole, 2019 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 50.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.41.70.5040.000Berard - Fluconazole, 2019Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016De Santis - Itraconazole, 2009Bar-Oz - Itraconazole, 2000Mastroiacovo - Fluconazole, 1996

Asymetry test p-value = 0.7079 (by Egger's regression)

slope=0.8702 (0.2653); intercept=-0.9596 (2.3278); t=0.4122; p=0.7079

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) 2.01[1.34; 3.00]30,2906,53888%NABerard - Fluconazole, 2019 Molgaard-Nielsen - Fluconazole (Oral) (Controls unexposed, NOS), 2016 De Santis - Itraconazole, 2009 Bar-Oz - Itraconazole, 2000 Mastroiacovo - Fluconazole, 1996 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.44[1.14; 1.82]2833,018 -NAMolgaard-Nielsen - Fluconazole (Oral) (Controls exposed to pivmecillinam), 2016 10.510.01.0