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Vitamin D Insufficiency in HIV-infected Pregnant Women Receiving Antiretroviral Therapy is Not Associated With Morbidity, Mortality or Growth Impairment in Their Uninfected Infants in Botswana

Powis, Kathleen MD, MPH*†‡; Lockman, Shahin MD, MSc†‡§; Smeaton, Laura MS; Hughes, Michael D. PhD; Fawzi, Wafaie MBBS, DrPH; Ogwu, Anthony MBBS; Moyo, Sikhulile MSc, MPH; van Widenfelt, Erik; von Oettingen, Julia MD**; Makhema, Joseph MB, ChB, MRCP; Essex, Max DVM, PhD†‡; Shapiro, Roger L. MD, MPH†‡††

Pediatric Infectious Disease Journal: November 2014 - Volume 33 - Issue 11 - p 1141–1147
doi: 10.1097/INF.0000000000000428
HIV Reports

Background: Low maternal 25(OH)D (vitamin D) values have been associated with higher mortality and impaired growth among HIV-exposed uninfected (HEU) infants of antiretroviral (ART)-naive women. These associations have not been studied among HEU infants of women receiving ART.

Methods: We performed a nested case-control study in the Botswana Mma Bana Study, a study providing ART to women during pregnancy and breastfeeding. Median maternal vitamin D values, and the proportion with maternal vitamin D insufficiency, were compared between women whose HEU infants experienced morbidity/mortality during 24 months of follow-up and women with nonhospitalized HEU infants. Growth faltering was assessed for never hospitalized infants attending the 24-month-of-life visit. Multivariate logistic regression models determined associations between maternal vitamin D insufficiency and infant morbidity/mortality and growth faltering.

Results: Delivery plasma was available and vitamin D levels assayable from 119 (86%) of 139 cases and 233 (84%) of 278 controls, and did not differ significantly between cases and controls [median: 36.7 ng/mL, interquartile range (IQR): 29.1–44.7 vs. 37.1 ng/mL, IQR: 30.0–47.2, P = 0.32]. Vitamin D insufficiency (<32 ng/mL) was recorded among 112 (31.8%) of 352 women at delivery and occurred most frequently among women delivering in winter. Multivariate logistic regression models adjusted for maternal HIV disease progression did not show associations between maternal vitamin D insufficiency at delivery and child morbidity/mortality, or 24-month-of-life growth faltering.

Conclusions: Vitamin D insufficiency was common among ART-treated pregnant women in Botswana, but was not associated with morbidity, mortality or growth impairment in their HIV-uninfected children.

From the *Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; §Brigham and Women’s Hospital, Infectious Disease Division; Center for Biostatistics in AIDS Research, Harvard School of Public Health; Department of Global Health and Population, Harvard School of Public Health; **Division of Endocrinology, Boston Children’s Hospital; and ††Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA.

Accepted for publication May 4, 2014.

The trial registration number was Clinical Registration Number: NCT00270296.

M.D.H. has served as a paid Data Safety and Monitoring Board member for Boehringer Ingelheim, Pfizer, Tibotec and Medicines Development. L.S. served as a paid Data Monitoring Committee member for Pfizer.

Mma Bana study was supported by a grant (U01-AI066454) from the National Institute of Allergy and Infectious Diseases. Funding support from Brigham and Women’s Global Women’s Health Fellowship supported K.P.’s salary during the Mma Bana study. K.P. received salary support from a Harvard University Center for AIDS Research grant (P30 AI060354) and a National Institute of Child Health and Human Development Grant (1K23HD070774-01A1) for this project. The Fogarty AITRP grant (D43 TW000004) provided funding for A.O. and S.M. Mma Bana study drugs were provided by Abbott Pharmaceuticals, GlaxoSmithKline, and the government of Botswana.

K.P., W.F., L.S., M.D.H., S.L., A.O., S.M., J.M., M.E., R.L.S., Vitamin D insufficiency in HIV-infected women on HAART is not associated with morbidity, mortality or growth impairment of uninfected infants in Botswana. 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, USA. March 3 to March 6, 2013. Abstract #920.

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Address for correspondence: Kathleen Powis, MD, MPH, 100 Cambridge St, 15th floor, Boston, MA 02114. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.