NEW YORK (Reuters Health) – Children exposed to or infected by HIV in utero may have worse neurodevelopmental outcomes than those who were not exposed to the virus during gestation, researchers suggest.
Dr. Megan McHenry, of Indiana University in Indianapolis, and colleagues 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).
As reported online January 26 in Pediatrics, the systematic review summarized data from 45 studies of 46 cohorts: 20 from the U.S., 18 from sub-Saharan Africa, 4 from Europe, 3 from South America, and one from Asia. The studies had been published from January 1990 to January 2017.
Eleven of those studies were included in the meta-analysis because they contained Bayley Scales of Infant and Toddler Development scores.
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, according to the authors.
In addition, 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, the authors note. In addition, all included studies had at least one methodological flaw.
In 28 studies, researchers indicated HIV+ children had worse developmental outcomes relative to comparison group(s); in three studies, HEU children had worse developmental outcomes than HUU children.
Of the latter finding, Dr. McHenry said, “one wonders what might be happening (to HEU) children in utero or after birth that is affecting them. More research is needed to answer that question.”
Rates of developmental delay varied considerably across studies. For example, among HIV+ children, rates of severe cognitive delays varied from 3% to 90%.
“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. “We do know that good nutrition and health, nurturing environments, and stimulating play all help promote positive development in all children. By providing these experiences for their child, as well as being compliant with ART during pregnancy, HIV-infected mothers will be maximizing the developmental potential of their children.”
Dr. Amanda Evans, Pediatric Infectious Disease Specialist at Children’s Health and Assistant Professor of Pediatrics, Division of Infectious Diseases at UT Southwestern Medical Center in Dallas told Reuters Health, “I agree with the authors’ findings that, taken as a whole, HIV-infected children likely have worse developmental outcomes compared to other children.”
“However, there are a number of subtle but important limitations to this study, some of which the authors address, which need to be further explored,” she said by email.
“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.”
“In my experience, children with uncontrolled HIV infection tend to fare worse than children with well-controlled HIV infection,” she added. “The authors did not address this aspect in their analysis. It may be misleading to examine these groups as a single cohort.”
“As the authors observe,” she continued, “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 prompt introduction of early childhood developmental interventions may help such children.”
SOURCE: http://bit.ly/2neW3Jk
Pediatrics 2018.
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