Children exposed to or infected with HIV in utero may have worse neurodevelopmental outcomes than those who were not exposed to the virus during gestation, researchers suggest. The findings are reported online in Pediatrics

Researchers conducted a systematic review and meta-analysis comparing neurodevelopmental performance in children infected with HIV (HIV+), those exposed to HIV in utero but uninfected (HEU), and those who were neither exposed nor infected (HUU).

The systematic review summarized data from 45 studies of 46 cohorts.Within the meta-analysis, when compared with their HUU peers, HIV+ and HEU children had lower Mental Development Index (cognitive) and Psychomotor Development Index (motor) scores.

Besides, HIV+ and HEU children exposed to antiretroviral therapy (ART) also had lower cognitive and motor scores compared with those without ART exposure, although the authors urge caution regarding this finding.

As Dr. McHenry told Reuters Health by email, other studies “have shown that early ART for HIV-infection improves neurodevelopment in infants. Additionally, early ART also improves growth and immune function while reducing the number of infant deaths, making it critically important for children born to HIV-infected mothers.”

Results of the systematic review were heterogeneous because of the number of neurodevelopmental assessments used. In addition, all included studies had at least one methodological flaw.

In 28 studies, researchers indicated HIV+ children had worse developmental outcomes relative to the comparison group(s); in three studies, HEU children had worse developmental outcomes than HUU children.Rates of developmental delay varied considerably across studies. 

“The cause of worse development in children born to HIV-infected mothers is still unknown, but multiple factors likely play a role,” Dr. McHenry concluded.

Dr. Amanda Evans, Pediatric Infectious Disease Specialist told Reuters Health that HIV-infected children likely have worse developmental outcomes compared to other children.

“The studies included in the meta-analysis ranged over two decades,” she noted, “during which time, many advances in the care of children occurred – including the availability of newer, safer, and more efficacious medications.”

Multiple potential confounders can impact the neurodevelopment of children. In Dallas, children born to HIV-positive mothers are more likely to come from resource-poor settings, with a higher proportion born to teen mothers or mothers dealing with substance abuse.”

“It is unclear from this meta-analysis whether the control subjects (non-HIV infected or exposed) included children from the same background,” Dr. Evans observed. “If not, this could also bias the results of the unexposed group.”

“Therefore, I would consider the possibility that the ‘worse neurodevelopmental outcomes’ found by the authors among HIV-exposed children may have been in part due to other aspects of their environment,” she suggested, “rather than a relatively brief exposure to antiretrovirals.

“That said, the study does highlight the overall vulnerability of the HIV-exposed,” she concluded. “This is an important finding, as a prompt introduction of early childhood development interventions may help such children.”