Exposure to HIV In Utero May Lead to Poor Neurodevelopment in Children

Investigators assessed neurodevelopment outcomes among uninfected children exposed to HIV infection and different maternal antiretroviral therapy regimens.

Results of a systematic review and meta-analysis published in The Lancet Child & Adolescent Health found that uninfected children exposed to HIV infection in utero were at risk for developing mild impairments in expressive language skills and gross motor development by 2 years of age.

Investigators at the Red Cross War Memorial Children’s Hospital searched publication databases through May 2020 for studies that assessed the effects of in utero exposure to maternal antiretroviral therapy (ART) on neurodevelopment in early childhood. The primary outcomes assessed were cognitive, receptive and expressive language, fine and gross motor development, and social and emotional adaptive behavior. 

The final analysis comprised 31 studies, of which 21 compared neurodevelopment between uninfected children exposed to HIV infection vs HIV-unexposed children and 10 compared the effects of in utero exposure to different maternal ART regimens. Most studies (79%) were conducted in Africa.

Results of approximately half of the studies (57%) that assessed neurodevelopment showed that outcomes were worse among children exposed to HIV infection compared with unexposed children. Of the remaining 9 studies on neurodevelopment, 8 showed no differences between exposed vs unexposed children, and 1 showed exposed children had better social and emotional development.

Compared with HIV-unexposed children, uninfected children exposed to HIV infection had worse expressive language skills (effect size [ES], -0.17; 95% CI, -0.27 to -0.07; P =.0013; I2, 55.44%) and worse gross motor development (ES, -0.13; 95% CI, -0.20 to -0.07; P <.0001; I2, 0%). No differences were observed for cognitive, receptive language, or fine motor development.

After stratification of HIV-unexposed and exposed children by age (12 vs 24 months), differences in expressive language skills were observed at 24 months, but outcomes of gross motor development were similar at both 12 and 24 months.

In the 10 studies that compared the effect of different maternal ART regimens, 75% of the included children were exposed to ART regimens comprising 3 different drug classes and 25% were exposed to zidovudine monotherapy. In 1 study, findings showed that exposure to atazanavir-based ART resulted in worse expressive language skills, especially if exposure occurred within the second or third trimester. However, these findings were observed only at 12 months of age.

This meta-analysis was limited by substantial heterogeneity among the included studies.

Despite the small effect sizes, the investigators observed “subtle yet clear” differences in neurodevelopment outcomes between HIV-unexposed vs exposed children. According to the investigators, “[future] studies should consider factors that are known to affect child neurodevelopment at the design stage, such as low birth weight and preterm birth, small for gestational age, hearing impairment, genetic syndromes, and neurologic disorders.”, 

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Wedderburn CJ, Weldon E, Bertran-Cobo C, et al. Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis. Lancet Child Adolesc Health. Published online April 25, 2022. doi:10.1016/S2352-4642(22)00071-2