In-utero HIV exposure and postnatal growth to 8 years of age: a prospective cohort study in the Western Cape, South Africa.

backgroundThe global scale-up of antiretroviral therapy for people living with HIV has led to an increase in children who are HIV-exposed uninfected (HEU), almost a quarter of whom lived in South Africa in 2024. These children might have suboptimal growth compared with children who are HIV-unexposed (HU), but few data are available beyond early childhood. We therefore evaluated differences in anthropometry by HIV exposure status from birth or from age 6 weeks, up to 8 years.

methodsThe Drakenstein Child Health Study-a prospective, longitudinal cohort study in the Western Cape of South Africa-recruited adult (age ≥18 years) women with and without HIV at 20-28 weeks' gestation from two primary health-care centres during routine antenatal care. Women and their liveborn children were followed up at least annually until age 8 years. The primary outcome was differences in anthropometry at birth or age 6 weeks and postnatally by HIV exposure, which was assessed at least annually by trained study staff and converted to sex-specific weight-for-age Z scores (WAZ), length-for-age or height-for-age Z scores (HAZ), and BMI-for-age Z scores (BMIZ) per WHO growth standards. All outcomes were assessed in all children with anthropometry data after birth. Stunting (HAZ <-2 SD from age 12 months) and overweight (BMIZ >2 SD from age 6 months) were secondary outcomes. Mixed-effects models adjusted for size at birth and prenatal covariates were used to estimate overall and age-specific associations between in-utero HIV-exposure status and WAZ, HAZ, BMIZ, stunting, and overweight from age 6 weeks to 8 years.

findings1225 pregnant women were enrolled from March 5, 2012, to March 31, 2015. 88 women were ineligible or withdrew and the remaining 1137 delivered 1143 livebirths, of whom 71 children were ineligible or withdrew. The remaining 1072 children (HEU 236 [22·0%] vs HU 836 [78·0%]) were enrolled and followed up until age 8 years. Mean birthweight was 3035 g (SD 592; HEU 3012 g [598] vs HU 3041 g [590]) and 168 (15·7%) of 1070 infants were preterm (HEU 43 [18·3%] of 235 vs HU 125 [15·0%] of 835). In overall multivariable estimates, children who were HEU had lower overall WAZ (marginal difference -0·16 [95% CI -0·32 to -0·01]) and HAZ (-0·26 [-0·41 to -0·11]) from age 6 weeks to 8 years compared with children who were HU. Age-specific differences were largest before age 6 months for WAZ and before age 3 years for HAZ. In overall multivariable estimates, there was no association between HIV exposure and BMIZ (-0·02 [-0·17 to 0·12]), stunting (0·05 [-0·04 to 0·13]), or overweight (-0·01 [-0·04 to 0·02]) from age 6 weeks to 8 years.

interpretationCompared with children who were HU, children who were HEU had lower overall WAZ and HAZ from age 6 weeks to 8 years, with the largest differences in early childhood. Early-life growth deficits are predictors of adverse health outcomes in later life; therefore, future work should focus on understanding the causes of growth deficits to improve health outcomes for children who are HEU. Interventions to optimise growth for all children in South Africa remain crucial.

fundingThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The Gates Foundation, and the National Health and Medical Research Council (Australia).