Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy

George K Siberry, Denise L Jacobson, Heidi J Kalkwarf, Julia W Wu, Linda A DiMeglio, Ram Yogev, Katherine M Knapp, Justin J Wheeler, Laurie Butler, Rohan Hazra, Tracie L Miller, George R Seage 3rd, Russell B Van Dyke, Emily Barr, Mariam Davtyan, Lynne M Mofenson, Kenneth C Rich, Pediatric HIV/AIDS Cohort Study, Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Shearer, Mary Paul, Norma Cooper, Lynnette Harris, Shelley Buschur, Murli Purswani, Emma Stuard, Anna Cintron, Mildred Maldonado, Katherine Knapp, Kim Allison, Megan Wilkins, Pam Henry, Stephanie Nelson, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Chi Dola, Robert Maupin, Karen Craig, Patricia Sirois, Shantrice Joseph, Marilyn Crain, Newana Beatty, Dan Marullo, Paige Hickman, Elizabeth McFarland, Jenna Wallace, Carrie Chambers, Christine Reed, Lilian Millan, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Kenneth Rich, Lourdes Richardson, Renee Smith, Toni Frederick, Mariam Davtyan, Maribel Mejia, Paul A Krogstad, Violeta Crow, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio, George K Siberry, Denise L Jacobson, Heidi J Kalkwarf, Julia W Wu, Linda A DiMeglio, Ram Yogev, Katherine M Knapp, Justin J Wheeler, Laurie Butler, Rohan Hazra, Tracie L Miller, George R Seage 3rd, Russell B Van Dyke, Emily Barr, Mariam Davtyan, Lynne M Mofenson, Kenneth C Rich, Pediatric HIV/AIDS Cohort Study, Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, William Shearer, Mary Paul, Norma Cooper, Lynnette Harris, Shelley Buschur, Murli Purswani, Emma Stuard, Anna Cintron, Mildred Maldonado, Katherine Knapp, Kim Allison, Megan Wilkins, Pam Henry, Stephanie Nelson, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Chi Dola, Robert Maupin, Karen Craig, Patricia Sirois, Shantrice Joseph, Marilyn Crain, Newana Beatty, Dan Marullo, Paige Hickman, Elizabeth McFarland, Jenna Wallace, Carrie Chambers, Christine Reed, Lilian Millan, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Kenneth Rich, Lourdes Richardson, Renee Smith, Toni Frederick, Mariam Davtyan, Maribel Mejia, Paul A Krogstad, Violeta Crow, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio

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.

Keywords: HIV; infant bone mineral content; intrauterine exposure; tenofovir.

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.

Figures

Figure 1.
Figure 1.
Participants were enrolled 2 April 2011 to 4 June 2013 during pregnancy (gestation age ≥23 weeks) through 2 weeks after birth. Eligibility was confirmed at birth for those enrolled before birth; 21 infants were excluded for the following reasons: gestational age less than 36 weeks (N = 16, 1 of whom was fetal demise), born at another hospital (N = 1), stillborn (N = 1), mother lost custody of child (N = 1), disqualifying change in maternal antiretroviral regimen during pregnancy (N = 2). Abbreviations: DXA, dual-energy X-ray absorptiometry; TDF, tenofovir disoproxil fumarate.

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