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

Abstract

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 < or =-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.

Conclusions: 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.

Fig 1

Longitudinal changes in growth patterns in children born to HIV-1–infected women. The time trend lines are the model-based means and 95% CIs graphed according to age and HIV status. A, B, and C, Weight (kg), height (cm), and weight for height for HIV-1–infected children (N = 92) and HIV-1–uninfected children (N = 439). D, E, and F, z Scores for weight, height, and weight for height for HIV-1–infected children (N = 92) and HIV-1–uninfected children (N = 439).

Fig 2

Cumulative rates of failure to thrive (FTT) and 95% CIs by HIV-1 status. A, 92 HIV-1–infected children; B, 439 HIV-1–uninfected children.

Fig 3

Cumulative rates of mortality by FTT status among 92 HIV-1–infected children. Children with FTT (N = 42) had higher mortality rates than did children without FTT (N = 50, P = .02).

Fig 4

Cumulative rates of FTT by disease progression among 92 HIV-1–infected children. Rapid progressors (RP, N = 45) had higher FTT rates than non–rapid progressors (N = 47, P = .001).