Early Cognitive and Motor Development Among Infants Born to Women Infected With Human Immunodeficiency Virus

Objective. To examine the frequency, timing, and factors associated with abnormal cognitive and motor development during the first 30 months of life in infants born to women infected with human immunodeficiency virus type 1 (HIV-1). Methods. Serial neurodevelopmental assessment was performed with 595 infants born to women infected with HIV-1 in a multicenter, prospective, natural history cohort study. Survival analysis methods were used to evaluate 6 outcome events related to abnormal cognitive and motor growth (time to confirmed drop of 1 SD, time to first score <69, and time to confirmed drop of 2 SD) in Bayley Scales of Infant Development Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores among infected (n 5 114) and uninfected (n 5 481) infants. Proportional hazards modeling was used to evaluate the effects of HIV infection status, prematurity, prenatal exposure to illicit drugs, maternal educational attainment, and primary language. Results. HIV-1 infection was significantly associated with increased risk for all outcome events related to abnormal mental and motor growth. Differences between infected and uninfected infants were apparent by 4 months of age. Prematurity was associated with increased risk for MDI <69 and PDI <69. Maternal education of <9 completed years was associated with increased risk for MDI <69. Neither prenatal exposure to illicit drugs nor primary language other than English was associated with abnormal development. Conclusion. A significant proportion of infants with HIV-1 infection show early and marked cognitive and motor delays or declines that may be important early indicators of HIV disease progression. These abnormalities are independent of other risk factors for developmental delay. Pediatrics 2000;106(2). URL: http://www. pediatrics.org/cgi/content/full/106/2/e25; human immunodeficiency virus, child development. ABBREVIATIONS. HIV-1, human immunodeficiency virus type 1; AIDS, acquired immunodeficiency syndrome; WITS, Women and Infants Transmission Study; MDI, Mental Developmental Index; PDI, Psychomotor Developmental Index; BSID, Bayley Scales of Infant Development; SD, standard deviation; RR, risk ratio; CI, confidence interval. Neurological and developmental signs are often early markers of human immunodeficiency virus type 1 (HIV-1) disease in infants that may precede other signs of disease progression.1 Numerous observational data describe the frequency of severe neurodevelopmental abnormalities in pediatric HIV disease. A prospective study of French children with congenital or perinatal HIV-1 infection reported a 19% rate of significant central nervous system impairment.2 The European Collaborative Study reported a 13% rate of serious neurological signs and symptoms in infected children and a much higher rate (31%) in children with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.3 A recent multicenter epidemiologic study in the United States showed HIV-1 encephalopathy diagnosed in 23% of children with perinatally acquired AIDS.4 HIV encephalopathy was present in 15% of US pediatric AIDS cases reported in 19945 and 18% in 1995.6 However, the frequency and timing of early and less severe neurodevelopmental effects of HIV infection, and the interaction with other known risk factors for developmental impairment, are not wellcharacterized. Previous published analyses of neurodevelopmental abnormality in children with HIV-1 disease have been cross-sectional in design or had small sample size, reporting differences between HIV-infected and HIV-exposed but HIV-uninfected infants in mean scores on neurodevelopmental measures at specific ages.7–9 These studies generally have not adjusted for other important risk factors related to neurodevelopmental abnormality besides HIV status. The Women and Infants Transmission Study (WITS) is an ongoing observational study of maternal–infant HIV transmission and outcome in women infected with HIV-1 and their children. Accrual began in 1989, and From the *Department of Pediatrics, Division of Infectious Disease, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts; ‡Department of Pediatrics, Division of Infectious Diseases, Children’s Hospital, Harvard Medical School, Boston, Massachusetts; §Health Science Center, Brooklyn and State University of New York, Brooklyn, New York; iDepartment of Pediatrics, University of Puerto Rico, San Juan, Puerto, Rico; ¶Department of Pediatrics, University of Illinois, Urbana, Illinois; #Department of Pediatrics, Baylor College of Medicine, Houston, Texas; **Department of Pediatrics, Columbia-Presbyterian Hospital, New York, New York; ‡‡Division of Acquired Immunodeficiency Syndrome, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; §§Pediatric Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, Washington, DC; and iiNew England Research Institutes, Watertown, Massachusetts. Received for publication Dec 8, 1998; accepted Feb 22, 2000. Reprint requests to (C.C.) Boston Medical Center, DLG 7, One Boston Medical Center Pl, Boston, MA 02118-2393. E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2000 by the American Acad-