Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa

Objectives: To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART). Design: Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother-infant pairs through 12-18 months postpartum. Setting: Peri-urban community, Cape Town, South Africa. Participants: HEU (n=215) and HIV-unexposed (n=306) children. Main outcome measures: Cognitive, motor and language development at median 13 (interquartile range 12-14) months of age: continuous and dichotomous Bayley Scales of Infant and Toddler Development Third Edition (delay defined as composite score <85). Results: Incidence of preterm delivery (<37 weeks) was similar among HEU and HIVunexposed children (11 vs. 9%, P=0.31; median gestation 39 weeks); 48% were boys. MedianbreastfeedingdurationwasshorteramongHEUvs.HIV-unexposedchildren(6vs.10 months). All HIV-infected mothers initiated lifelong ART (tenofovir-emtricitabine-efavirenz) antenatally.HEU(vs.HIV-unexposed)childrenhadhigheroddsofcognitivedelay[odds ratio(OR)2.28(95%confidenceinterval (CI)1.13-4.60)]andmotordelay[OR2.10(95%CI 1.03-4.28)], but not language delay, in crude and adjusted analysis. Preterm delivery modified this relationship for motor development: compared with term HIV-unexposed children, termHEUchildrenhadsimilaroddsofdelay, pretermHIV-unexposedchildrenhad five-fold increased odds of delay (adjustedOR 4.73, 95%CI 1.32; 16.91) and preterm HEU children, 16-fold increased odds of delay (adjusted OR 16.35, 95% CI 5.19; 51.54). Conclusion: Young HEU children may be at increased risk for cognitive and motor delay despite universal maternal ART and breastfeeding; those born preterm may be particularly vulnerable.