Stunting Among HIV-Uninfected Children Perinatally Exposed to Maternal-HIV and Antiretroviral Drugs Compared to Unexposed Controls in Malawi and Uganda: A Prospective Study

Abstract

Background: Antiretroviral drug and HIV exposed uninfected (AHEU) children were associated with growth deficits in some but not all previous studies which had considerable limitations. Objective: To compare anthropometric outcomes among AHEU, and HIV unexposed uninfected (HUU) children at 12 and 24-months-of-age. Design: Prospective cohort of AHEU children co-enrolled from the PROMISE randomized clinical trial (NCT01061151: clinicaltrials.gov registry); and age-and-sex-matched HUU controls enrolled from child-wellness clinics, between 09/2013-10/2014 in Malawi and Uganda. Methods: Standardized anthropometric and clinical data were collected at 12 and 24-months-of-age. We used WHO-population (2006) growth-standards to derive weight-for-age (WAZ); length-for-age (LAZ); weight-for-length (WLZ); and head-circumference-for-age (HCAZ) z-scores. Wilcoxon Rank-Sum/Fischer's exact tests were used for AHEU and HUU comparisons; and Generalized-Estimating-Equations models controlling for maternal-age, tap-water, electricity/gas, and breastfeeding status were used to estimate adjusted relative risk (aRR). Findings: Overall, 472 (50.5%) AHEU and 462 (49.5%) HUU children were assessed. Ugandan AHEU compared to HUU children had significantly lower mean-Z-scores: LAZ (p 0.05). The risk of stunting (more than two standard deviations below the WHO-population LAZ median) was increased among AHEU compared to HUU children: aRR=2.13 (95% confidence interval (CI): 1.36, 3.33), p=0.001, at 12-months, and aRR=1.67 (95% CI: 1.16, 2.41), p=0.006, at 24-months-of-age, in Uganda; and aRR=1.32 (95% CI: 1.10, 1.66), p=0.018, at 24-months-of-age, in Malawi. Relative-risk of HCAZ below WHO median was increased among AHEU children at 24-months-of-age, aRR = 1.35 (95% CI: 1.02, 1.79), p=0.038, in Uganda; and in similar direction but not significant, aRR=1.35 (95% CI: 0.91, 2.02), p=0.139, in Malawi. Interpretation: Perinatal maternal-HIV and ARV exposures were associated with lower LAZ (including stunting), WAZ and HCAZ at 24 months-of-age compared to sex and age-matched HUU children from similar socioeconomic backgrounds. Funding Statement: The study was funded by the US National Institute of Child Health and Human Development (HD 073296). Declaration of Interests: The authors do not have financial, consultant, institutional or other relationships that might lead to a bias or conflict of interest. Ethics Approval Statement: Regulatory oversight was provided by Institutional Review Boards in Malawi and Uganda, and the Johns Hopkins Medical Institute.