title: Fluconazole use and birth defects in the National Birth Defects Prevention Study.
abstract: BACKGROUND
  Low-dose fluconazole is used commonly to treat vulvovaginal candidiasis, a condition occurring frequently during pregnancy. Conflicting information exists on the association between low-dose fluconazole use among pregnant women and the risk of major birth defects.
  
  
  OBJECTIVE
  We used data from the National Birth Defects Prevention Study to examine this association.
  
  
  METHODS
  The National Birth Defects Prevention Study is a multisite, population-based, case-control study that includes pregnancies with estimated delivery dates from 1997 to 2011. Information on fluconazole use in early pregnancy was collected by self-report from 31,645 mothers of birth defect cases and 11,612 mothers of unaffected controls. Adjusted odds ratios and 95% confidence intervals were estimated for birth defects with 5 or more exposed cases; crude odds ratios and exact 95% confidence intervals were estimated for birth defects with 3-4 exposed cases.
  
  
  RESULTS
  Of the 43,257 mothers analyzed, 44 case mothers and 6 control mothers reported using fluconazole. Six exposed infants had cleft lip with cleft palate, 4 had an atrial septal defect, and each of the following defects had 3 exposed cases: hypospadias, tetralogy of Fallot, d-transposition of the great arteries, and pulmonary valve stenosis. Fluconazole use was associated with cleft lip with cleft palate (odds ratio = 5.53; confidence interval = 1.68-18.24) and d-transposition of the great arteries (odds ratio = 7.56; confidence interval = 1.22-35.45).
  
  
  CONCLUSIONS
  The associations between fluconazole and both cleft lip with cleft palate and d-transposition of the great arteries are consistent with earlier published case reports but not recent epidemiologic studies. Despite the larger sample size of the National Birth Defects Prevention Study, fluconazole use was rare. Further investigation is needed in large studies, with particular emphasis on oral clefts and conotruncal heart defects.
authors.affiliation: Congenital Malformations Registry, New York State Department of Health, Albany, NY. Electronic address: meredith.howley@health.ny.gov.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Howley
authors.affiliation: Center for Human Genetics, Marshfield Clinic, Marshfield, WI.
authors.forename: Tonia C
authors.initials: TC
authors.lastname: Carter
authors.affiliation: Congenital Malformations Registry, New York State Department of Health, Albany, NY; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY.
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Browne
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, NY.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Cunniff
authors.affiliation: Congenital Malformations Registry, New York State Department of Health, Albany, NY; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects*; D002177:Candidiasis / Q000188:drug therapy; D016022:Case-Control Studies; D005260:Female; D015725:Fluconazole / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole
keywords: birth defect; congenital malformation; fluconazole