In-utero exposure to antiretrovirals and neurodevelopment among HIV-exposed-uninfected children in Botswana

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Abstract

Objective:

Conflicting data exist regarding the impact of in-utero exposure to maternal combination antiretrovirals. We compared neurodevelopmental outcomes between HIV-exposed-uninfected (HEU) children exposed in utero to three-drug combination antiretroviral therapy (ART) vs. zidovudine (ZDV) monotherapy.

Design:

Prospective study of child neurodevelopment, nested within two cohorts of HIV-infected mothers and their children in Botswana (one observational, one interventional).

Methods:

The Tshipidi and Mma Bana studies enrolled HIV-infected women during pregnancy and followed their HEU children for 24 months. Mothers took three-drug ART or ZDV during pregnancy. ART-exposed babies were mostly breastfed, and ZDV-exposed were formula-fed. Neurodevelopmental outcomes, measured at 24 months using Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) and Development Milestones Checklist (DMC), were compared in adjusted linear regression according to antiretroviral exposure.

Results:

Of 598 HEU children with valid neurodevelopment assessments, 382 were ART-exposed and 210 were ZDV-exposed. Adjusted mean Bayley-III scores were similar among ART-exposed vs. ZDV-exposed, with adjusted mean differences (95% confidence interval): Bayley-III Cognitive: −0.3 (−1.4, 0.9); Gross Motor: 0.8 (−0.1, 1.7); Fine Motor: 0.5 (−0.2, 1.3); Expressive Language: 0.7 (−0.3, 1.7); Receptive Language: 0.1 (−0.7, 0.8); and DMC Locomotor: 0.0 (−0.5, 0.6); Fine Motor: 0.3 (−0.3, 0.8); Language: −0.1 (−0.5, 0.4); Personal-Social: 0.2 (−0.7, 1.1). Similarly, when restricted to formula-fed children in one cohort (Tshipidi), there were no differences in adjusted mean scores.

Conclusion:

Neurodevelopmental outcomes at 24 months of age were similar in ART-exposed vs. ZDV-exposed HEU children. Maternal ART with breastfeeding does not appear to have an adverse effect on neurodevelopment.

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