Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth

Mølgaard-Nielsen, Ditte; Svanström, Henrik; Melbye, Mads; Hviid, Anders; Pasternak, Björn

doi:10.1001/jama.2015.17844

Cited by 87 publications

(82 citation statements)

References 35 publications

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“…However, some miscarriages may not be registered because of unawareness of pregnancy or missing hospital referral. Our study relied on hospital diagnoses and we restricted miscarriages to gestational weeks 7‐21 . It is likely that awareness of pregnancy is greater in women with surgery during early pregnancy than in women without surgery.…”

Section: Discussionmentioning

confidence: 99%

“…We calculated GA in days as GA(weeks)*7 + GA(days). Miscarriages before week 7 of gestation are poorly registered and were therefore not included . Live births at all GAs were registered in the DMBR.…”

Section: Methodsmentioning

confidence: 99%

“…Miscarriages before week 7 of gestation are poorly registered and were therefore not included. 26 Live births at all GAs were registered in the DMBR. We excluded births registered before week 22, the inclusion limit for miscarriages in the DNPR.…”

Section: And the Danish Medical Birthmentioning

confidence: 99%

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Non‐obstetric abdominal surgery during pregnancy and birth outcomes: A Danish registry‐based cohort study

Rasmussen

Christiansen

Ulrichsen

et al. 2019

Acta Obstet Gynecol Scand

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Introduction Surgery during pregnancy may increase the risk of adverse birth outcomes. In this nationwide registry‐based cohort study including women aged 15‐54 years with singleton birth or miscarriage, we examined the association between non‐obstetric abdominal surgery during pregnancy and the birth outcomes small‐for‐gestational‐age (SGA), preterm birth, and miscarriage. Material and methods The study used data on births or miscarriages from the large national Danish registries in 1997‐2015. We calculated absolute risks and risk differences for the main outcomes and used Cox regression analysis with non‐obstetric abdominal surgery as a time‐varying exposure, adjusting for maternal age, year of last menstrual period, major abdominal surgery before pregnancy, maternal smoking status, rheumatoid arthritis, diabetes and inflammatory bowel disease. Our main outcome measures were risks and hazard ratios (HRs) for SGA, very preterm or preterm birth, and miscarriage after gestational week 7 overall, stratified by calendar year, and, for SGA, trimester of pregnancy. Finally, absolute risk of miscarriage stratified by time since surgery. Results Absolute risks in surgically treated vs untreated were 3.4% vs 2.7% for SGA (adjusted HR 1.3, 95% CI 1.1‐1.5), 2.2% vs 0.8% for very preterm birth (adjusted HR 2.8, 95% CI 2.2‐3.5), 8.3% vs 4.3% for preterm birth (adjusted HR 2.1, 95% CI 1.9‐2.3), and 8.2% vs 6.1% for miscarriage (adjusted HR 3.1, 95% CI 2.7‐3.5). For miscarriage, the risk was highest the first week after surgery and levelled out after 2 weeks. Conclusions Surgery during pregnancy is associated with an increased risk of SGA, very preterm birth, preterm birth and miscarriage, and the risk of miscarriage is highest the first week after surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Non‐obstetric abdominal surgery during pregnancy and birth outcomes: A Danish registry‐based cohort study

Rasmussen

Christiansen

Ulrichsen

et al. 2019

Acta Obstet Gynecol Scand

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“…The nature of these birth defects suggests that the teratogenic effect may occur early in the first trimester and has been confirmed by at least one animal study . Several studies support the risk of low‐dose fluconazole during pregnancy, especially when used for short durations . One recent cohort study identified an association between oral fluconazole during pregnancy and the risk of spontaneous abortion .…”

Section: Systemic Azole Antifungalsmentioning

confidence: 99%

“…44,45 One recent cohort study identified an association between oral fluconazole during pregnancy and the risk of spontaneous abortion. 45 Women who were exposed to either low-dose (150-300 mg) or high-dose (350-5600 mg) fluconazole during 7 through 22 weeks' gestation were matched to unexposed pregnancies. Fluconazole-exposed women had a significantly increased risk of spontaneous abortion compared with unexposed women (147 of 3315 and 563 of 13,246 women, respectively; hazard ratio [HR] 1.48, 95% CI 1.23-1.77).…”

Section: Fluconazolementioning

confidence: 99%

A Review of Antiviral and Antifungal Use and Safety during Pregnancy

Cottreau

Barr

2016

Pharmacotherapy

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Antiviral and antifungal use in pregnancy presents challenges because of the paucity of clinical and safety data for many agents in these classes. If untreated, viral and fungal infections can have deleterious effects on both maternal and fetal health. Understanding the use and risks of these medications in pregnancy is vital to provide appropriate care. This article reviews the current literature for the use of antiviral and antifungals, the pharmacokinetics of these agents, and their safety in pregnancy.

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Oral Fluconazole in Pregnancy and Risk of Stillbirth and Neonatal Death

Pasternak

Wintzell

Furu

et al. 2018

JAMA

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Although treatment with oral fluconazole during pregnancy is generally discouraged, 1 approximately 4% of pregnant women in the United States use fluconazole. 2 There are concerns that fluconazole use may be associated with stillbirth, particularly in doses above those commonly used for the treatment of vaginal candidiasis (150 mg, administered once or twice). In a nationwide Danish study, 3 any fluconazole exposure was not associated with an increased risk of stillbirth, but the estimate had limited precision (hazard ratio [HR], 1.32 [95% CI, 0.82-2.14]); exposure to doses above 300 mg was associated with stillbirth (HR, 4.10 [95% CI, 1.89-8.90]). We investigated if fluconazole use during pregnancy is associated with stillbirth and neonatal death. Methods | Nationwide register data were used to identify all pregnancies with singleton live births and stillbirths in

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Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth

Cited by 87 publications

References 35 publications

Non‐obstetric abdominal surgery during pregnancy and birth outcomes: A Danish registry‐based cohort study

Non‐obstetric abdominal surgery during pregnancy and birth outcomes: A Danish registry‐based cohort study

A Review of Antiviral and Antifungal Use and Safety during Pregnancy

Oral Fluconazole in Pregnancy and Risk of Stillbirth and Neonatal Death

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