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PEDIATRICS Vol. 108 No. 6 December 2001, pp. 1287-1296

Maternal and Infant Factors Associated With Failure to Thrive in Children With Vertically Transmitted Human Immunodeficiency Virus-1 Infection: The Prospective, P²C² Human Immunodeficiency Virus Multicenter Study

Tracie L. Miller, MD^*, Kirk A. Easley, MS, Weihong Zhang, MS, E. John Orav, PhD, Dennis M. Bier, MD^||, Elisabeth Luder, PhD^¶, Andrew Ting, MD^¶, William T. Shearer, MD, PhD^**, Jorge Humberto Vargas, MD, Steven E. Lipshultz, MD, for the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P²C² HIV) Study Group^,* and National Heart, Lung, and Blood Institute, Bethesda, MD

^* Division of Pediatric Gastroenterology and Nutrition, University of Rochester Medical Center
Department of Biostatistics and Epidemiology, the Cleveland Clinic Foundation, Cleveland
Department of Medicine, Brigham and Women’s Hospital, Boston
^|| Children’s Nutrition Research Center, Texas Children’s Hospital, Houston
^¶ Department of Pediatrics, Mount Sinai School of Medicine, New York
^** Baylor College of Medicine, Department of Pediatrics, Division of Allergy and Immunology
UCLA Center for the Health Sciences, Los Angeles
Division of Pediatric Cardiology, University of Rochester Medical Center

Objective. Many children with human immunodeficiency virus-1 (HIV-1) have chronic problems with growth and nutrition, yet limited information is available to identify infected children at high risk for growth abnormalities. Using data from the prospective, multicenter P²C² HIV study, we evaluated the relationships between maternal and infant clinical and laboratory factors and impaired growth in this cohort.

Methods. Children of HIV-1-infected women were enrolled prenatally or within the first 28 days of life. Failure to thrive (FTT) was defined as an age- and sex-adjusted weight z score -2.0 SD. Maternal baseline covariates included age, race, illicit drug use, zidovudine use, CD4⁺ T-cell count, and smoking. Infant baseline predictors included sex, race, CD4⁺ T-cell count, Centers for Disease Control stage, HIV-1 RNA, antiretroviral therapy, pneumonia, heart rate, cytomegalovirus, and Epstein-Barr virus infection status.

Results. The study cohort included 92 HIV-1-infected and 439 uninfected children. Infected children had a lower mean gestational age, but birth weights, lengths, and head circumferences in the 2 groups were similar. Mothers of growth-delayed infants were more likely to have smoked tobacco and used illicit drugs during pregnancy. In repeated-measures analyses of weight and length or height z scores, the means of the HIV-1-infected group were significantly lower at 6 months of age (P < .001) and remained lower throughout the first 5 years of life. In a multivariable Cox regression analysis, FTT was associated with a history of pneumonia (relative risk [RR] = 8.78; 95% confidence interval [CI]: 3.59–21.44), maternal use of cocaine, crack, or heroin during pregnancy (RR = 3.17; 95% CI: 1.51–6.66), infant CD4⁺ T-cell count z score (RR = 2.13 per 1 SD decrease; 95% CI: 1.25–3.57), and any antiretroviral therapy by 3 months of age (RR = 2.77; 95% CI: 1.16–6.65). After adjustment for pneumonia and antiretroviral therapy, HIV-1 RNA load remained associated with FTT in the subset of children whose serum was available for viral load analysis.

Conclusion. Clinical and laboratory factors associated with FTT among HIV-1-infected children include history of pneumonia, maternal illicit drug use during pregnancy, lower infant CD4⁺ T-cell count, exposure to antiretroviral therapy by 3 months of age (non-protease inhibitor), and HIV-1 RNA viral load.

Key Words: human immunodeficiency virus • children • failure to thrive • growth • malnutrition

Abbreviations: HIV-1, human immunodeficiency virus-1 • FTT, failure to thrive • RDA, recommended daily allowance • P²C², Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection study • ZDV, zidovudine • CDC, Centers for Disease Control and Prevention • CMV, cytomegalovirus • EBV, Epstein-Barr virus • PCP, Pneumocystis carinii pneumonia • NOS, not otherwise specified • CI, confidence interval • RR, relative risk

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Received for publication Mar 16, 2001; Accepted Jul 20, 2001.

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