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Published online August 28, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. e1139-e1145 (doi:10.1542/peds.2006-0525)
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ARTICLE

A Prospective Controlled Study of Neurodevelopment in HIV-Uninfected Children Exposed to Combination Antiretroviral Drugs in Pregnancy

Ariane Alimenti, MDa, John C. Forbes, BSc, MB, ChB, FRCP(C)a, Tim F. Oberlander, MD, FRCP(C)a, Deborah M. Money, BSc, MD, FRCSCb, Ruth E. Grunau, BA, MA, EdD, PhD/RPsycha, Michael P. Papsdorf, PhDc, Evelyn Maan, RNd, Lesley J. Cole, RN, BSNe, David R. Burdge, BSc, MD, FRCP(C)d

a Departments of Pediatrics
b Obstetrics and Gynecology
d Medicine, University of British Columbia, Vancouver, British Columbia, Canada
c Centre for Community Child Health Research
e Maternal Fetal Medicine, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada

OBJECTIVE. Our intent was to investigate the neurodevelopment of HIV-uninfected children exposed to combination highly active antiretroviral therapy in pregnancy compared with children not exposed to highly active antiretroviral therapy but with similar socioeconomic backgrounds.

PATIENTS AND METHODS. A prospective controlled cross-sectional study of the neurodevelopment of children exposed to highly active antiretroviral therapy versus those not exposed was performed by using the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales at 18 to 36 months of age. The highly active antiretroviral therapy–exposed children were born to HIV-infected women but were uninfected themselves. The control children were born to HIV-uninfected women with similar anticipated socioeconomic background (hepatitis C infected and high proportion of substance use). Sociodemographic, clinical, highly active antiretroviral therapy (antenatal, intrapartum, neonatal), and substance-use histories were collected. Results were compared by using analyses of covariance and {chi}2 analysis.

RESULTS. Thirty-nine highly active antiretroviral therapy–exposed and 24 control children were assessed. All mean scores were lower for those in the highly active antiretroviral therapy–exposed group than those in the control group (Bayley Mental Development Index: 85.4 vs 94.3; Bayley Psychomotor Development Index: 93.4 vs 96.6; Vineland mean communication score: 90.1 vs 94.4; Vineland mean daily-living score: 91.2 vs 93.6; Vineland mean socialization score: 97.1 vs 98.4). However, when maternal substance use during pregnancy was controlled for, there were no significant differences between the groups in any domains assessed. Children in both groups exposed to maternal substance use scored significantly lower than children not exposed in all domains except communication skills. It is important to note that there were no differences between the highly active antiretroviral therapy–exposed children with no substance exposure and the control children with no substance exposure in any of the scores.

CONCLUSIONS. HIV- and highly active antiretroviral therapy–exposed HIV-uninfected children had lower development and adaptive behavior scores when compared with children who had not been exposed. However, these differences were not significant after correcting for maternal substance use, which had a greater impact on neurodevelopment than highly active antiretroviral therapy exposure. These results suggest that perinatal highly active antiretroviral therapy exposure is not associated with altered development and behavior at 18 to 36 months of age.

Key Words: HIV • child development • pregnancy • drug effects • anti-HIV agents • toxicity

Abbreviations: HAART—highly active antiretroviral therapy • BSID-II—Bayley Scales of Infant Development-II • MDI—Mental Development Index • PDI—Psychomotor Development Index

Accepted May 8, 2006.


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