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Mental Development Equivalent in ARV-Exposed and Unexposed Kids Without HIV
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XVII International AIDS Conference
August 3-8, 2008
Mexico City
Mark Mascolini
US children not infected with HIV by their seropositive mothers before or during birth, but exposed to antiretrovirals (ARVs) their mothers took, develop neurologically and cognitively as well as children not exposed to ARVs through their HIV-infected mothers [1]. This observational study--the largest assessing cognitive and motor development in ARV-exposed but uninfected children--allays some concerns over potential dangers of ARVs during gestation. But follow-up of these children lasted only to age 2 and ARVs may have other toxic effects not assessed in this study.
Paige Williams (Harvard University) and Pediatric AIDS Clinical Trials Group (PACTG) investigators studied 1840 infants born to HIV-infected mothers from 1993 through 2006 at 80 sites in the USA and Puerto Rico. Half of the children were girls, 55% black, and 32% Hispanic. PACTG investigators recorded low birth weight (below 2500 grams) in 294 children (16%).
Mothers of 1694 children (92%) took ARVs during pregnancy, so 146 children (8%) did not encounter ARVs before birth. ARV-exposed children were more likely to be born after 1994, but mothers or caregivers of exposed and unexposed children did not differ demographically.
The PACTG team analyzed Mental Development Index (MDI) and the Psychomotor Development Index (PDI) of children when they reached 2 years of age. Statistical analysis of MDI and PDI took into account potential confounding factors, including age, race, primary language, gender, primary caregiver, caregiver education level, low birth weight, geographical and urban versus rural location, birth year, and maternal use of heroin, cocaine, or stimulants.
Adjusted average MDI was marginally higher in ARV-exposed children than in their unexposed counterparts (94.8 versus 92.2, P = 0.07). Adjusted average PDI was similar in the two groups. Among children with low birth weight, adjusted MDI and PDI scores were 10 to 12 points higher in ARV-exposed children (P = 0.01 and P < 0.01). Antiretroviral therapy, Williams observed, may be associated with low birth weight. Notably, MDI and PDI scores in the whole study group lay significantly below norms in the US population, a finding that may reflect the socioeconomic status of the mothers and caregivers.
Use of heroin, cocaine, or stimulants during pregnancy (by 17% of mothers) had no effect on MDI or PDI, as substance abuse did in a smaller, earlier study of HIV-exposed but uninfected infants [2]. In the earlier study comparing 39 HIV-exposed children with 29 unexposed children with similar demographics, ARV exposure did not slow development after statistical adjustment for maternal substance abuse [2].
Williams cautioned that this analysis is limited by the 2-year follow-up cutoff, by reliance on self-report to gauge maternal substance abuse, and by potential biases inherent in any observational study. Socioeconomic status and access to prenatal care, she proposed, may differ between mothers who took ARVs and those who did not.
"While these results are reassuring," the PACTG investigators concluded, "continued evaluation of uninfected infants with in utero ARV exposure for late outcomes is important."
References
1. Williams P, Marino M, Malee K, et al. Neurodevelopmental status and prenatal antiretroviral exposure in HIV-exposed uninfected infants. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract MOAB0102.
2. Alimenti A, Forbes JC, Oberlander TF, et al. A prospective controlled study of neurodevelopment in HIV-uninfected children exposed to combination antiretroviral drugs in pregnancy. Pediatrics. 2006;118:e1139-e1145.
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