George K Siberry1, Denise L Jacobson2, Heidi J Kalkwarf3, Julia W Wu4, Linda A DiMeglio5, Ram Yogev6, Katherine M Knapp7, Justin J Wheeler8, Laurie Butler9, Rohan Hazra1, Tracie L Miller10, George R Seage4, Russell B Van Dyke11, Emily Barr12, Mariam Davtyan13, Lynne M Mofenson1, Kenneth C Rich14. 1. Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. 2. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 3. Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Ohio. 4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 5. Section of Pediatric Endocrinology/Diabetology, Department of Pediatrics, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis. 6. Lurie Children's Hospital, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 7. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee. 8. Tufts University Body Composition Analysis Center, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Boston, Massachusetts. 9. Frontier Science Technology and Research Foundation, Amherst, New York. 10. Department of Pediatrics, Miller School of Medicine at the University of Miami, Florida. 11. Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana. 12. Children's Hospital Colorado, Department of Infectious Disease, University of Colorado, Denver. 13. LAC+USC Maternal, Child & Adolescent Center for Infectious Diseases and Virology, Los Angeles, California. 14. Department of Pediatrics, University of Illinois at Chicago.
Abstract
BACKGROUND: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. METHODS: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. RESULTS: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. CONCLUSIONS: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01310023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. METHODS: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. RESULTS: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. CONCLUSIONS: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01310023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Entities:
Keywords:
HIV; infant bone mineral content; intrauterine exposure; tenofovir
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