title: Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01310023.
authors.affiliation: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacobson
authors.affiliation: Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Ohio.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Kalkwarf
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Julia W
authors.initials: JW
authors.lastname: Wu
authors.affiliation: Section of Pediatric Endocrinology/Diabetology, Department of Pediatrics, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, Indianapolis.
authors.forename: Linda A
authors.initials: LA
authors.lastname: DiMeglio
authors.affiliation: Lurie Children's Hospital, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Knapp
authors.affiliation: Tufts University Body Composition Analysis Center, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Boston, Massachusetts.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Wheeler
authors.affiliation: Frontier Science Technology and Research Foundation, Amherst, New York.
authors.forename: Laurie
authors.initials: L
authors.lastname: Butler
authors.affiliation: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.affiliation: Department of Pediatrics, Miller School of Medicine at the University of Miami, Florida.
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Miller
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.affiliation: Children's Hospital Colorado, Department of Infectious Disease, University of Colorado, Denver.
authors.forename: Emily
authors.initials: E
authors.lastname: Barr
authors.affiliation: LAC+USC Maternal, Child & Adolescent Center for Infectious Diseases and Virology, Los Angeles, California.
authors.forename: Mariam
authors.initials: M
authors.lastname: Davtyan
authors.affiliation: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Rich
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir
keywords: HIV; infant bone mineral content; intrauterine exposure; tenofovir