Meredith M Howley1, Tonia C Carter2, Marilyn L Browne3, Paul A Romitti4, Christopher M Cunniff5, Charlotte M Druschel3. 1. Congenital Malformations Registry, New York State Department of Health, Albany, NY. Electronic address: meredith.howley@health.ny.gov. 2. Center for Human Genetics, Marshfield Clinic, Marshfield, WI. 3. 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. 4. Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA. 5. Department of Pediatrics, Weill Cornell Medical College, New York, NY.
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. STUDY DESIGN: 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.
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. STUDY DESIGN: 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: John E Edwards; Michael M Schwartz; Clint S Schmidt; Jack D Sobel; Paul Nyirjesy; Florian Schodel; Erica Marchus; Mary Lizakowski; Elizabeth A DeMontigny; Jesse Hoeg; Tuomas Holmberg; M Timothy Cooke; Keila Hoover; Lance Edwards; Mark Jacobs; Steven Sussman; Michael Augenbraun; Michael Drusano; Michael R Yeaman; Ashraf S Ibrahim; Scott G Filler; John P Hennessey Journal: Clin Infect Dis Date: 2018-06-01 Impact factor: 9.079
Authors: Yanmin Zhu; Brian T Bateman; Kathryn J Gray; Sonia Hernandez-Diaz; Helen Mogun; Loreen Straub; Krista F Huybrechts Journal: BMJ Date: 2020-05-20