Maternal use of fluconazole and risk of congenital malformations: a Danish population-based cohort study.
OBJECTIVE
Fluconazole is widely used for the treatment of candidiasis. Although the drug is also prescribed to pregnant women, data on the safety of use of fluconazole during pregnancy are limited. We examined the association between the maternal use of fluconazole during pregnancy and the risk of congenital malformations.


METHODS
In this population-based cohort study in Northern Denmark, we included 1079 women who had a live birth or a stillbirth after the 20th week of gestation and who redeemed at least one prescription for fluconazole during the first trimester. The reference cohort comprised 170 453 pregnant women who redeemed no fluconazole prescription during pregnancy. The women were identified through the Danish Medical Birth Registry. Data on drug use, birth outcome and covariates were extracted from population-based healthcare databases. We used logistic regression to estimate the prevalence odds ratio (POR) for congenital malformations after fluconazole exposure, while adjusting for maternal smoking, parity, maternal age and concurrent prescriptions for antiepileptics or antidiabetics.


RESULTS
Among 1079 women who filled a fluconazole prescription during the first trimester, 797 (74%) received a total of 150 mg of fluconazole, 235 (22%) received 300 mg of fluconazole, 24 (2%) received 350 mg of fluconazole and 23 (2%) received 600 mg of fluconazole. These women gave birth to 44 (4.1%) children with congenital malformations. The 170 453 women without fluconazole prescriptions gave birth to 6152 (3.6%) children with congenital malformations. For congenital malformations overall, the adjusted POR associated with the first-trimester fluconazole use was 1.0 (95% confidence interval: 0.8-1.4).


CONCLUSIONS
We found no overall increased risk of congenital malformations after exposure to short-course treatment with fluconazole in early pregnancy.
Nørgaard
Mette
M
Department of Clinical Epidemiology, Aarhus University Hospital, Denmark. m.noergaard@rn.dk
Pedersen
Lars
L
Gislum
Mette
M
Erichsen
Rune
R
Søgaard
Kirstine Kobberøe
KK
Schønheyder
Henrik Carl
HC
Sørensen
Henrik Toft
HT
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000935:Antifungal Agents / Q000009:adverse effects*; D002177:Candidiasis / Q000188:drug therapy*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D015725:Fluconazole / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011248:Pregnancy Complications; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy
D000935:Antifungal Agents; D015725:Fluconazole