Early childhood diarrhea and growth among HIV-exposed, uninfected infants in Kenya
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Background: Diarrhea and poor linear growth are leading causes of childhood morbidity and mortality in low- and middle- income countries. While global childhood mortality has been significantly reduced in the past decades, further reductions will likely require a better understanding of the causes of and relationship between diarrhea and linear growth in vulnerable populations. The massive success of programs aimed at preventing mother-to-child transmission of HIV has resulted in a growing number of HIV-infected women giving birth to uninfected children. These HIV-exposed, uninfected (HEU) children, are an understudied and uniquely vulnerable population who experience higher rates of death and disability than their unexposed counterparts. These HEU children may be an important group to target for reducing diarrhea morbidity and linear growth faltering in order to further decrease global burden. Methods: This dissertation used data from a historical cohort of HIV-infected mothers and their uninfected infants followed from pregnancy to 12 months postpartum in Nairobi, Kenya. Infant and maternal illness, including diarrhea, were ascertained at monthly study visits and sick visits. Infant length was recorded at monthly study visits. Anderson-Gill Cox models assessed maternal, environmental, and infant correlates of diarrhea, moderate-to-severe diarrhea (MSD; diarrhea with dehydration, dysentery, or related hospital admission), and prolonged/persistent diarrhea (Chapter 1). Length-for-age z-scores (LAZ) were used to measure infant linear growth. Mixed-effects models estimated the difference in monthly LAZ from 0-12 months by environmental, maternal, and infant characteristics (Chapter 2). The relationship between diarrhea severity, treatment, burden, and timing and infant linear growth in the following month was tested throughout the first year of life using mixed-effects models (Chapter 3). Results: Chapter 1: Over the 12 month follow-up period, HEU infants (n=373) experienced a mean 2.09 (95% Confidence Interval [CI]: 1.93, 2.25) episodes of diarrhea, 0.47 (95% CI: 0.40, 0.54) episodes of MSD, and 0.34 (95% CI: 0.29, 0.42) episodes of prolonged/persistent diarrhea. Postpartum maternal diarrhea was associated with increased risk of infant diarrhea (Hazard Ratio [HR]: 2.09; 95%: 1.43, 3.06) and infant MSD (HR: 2.89; 95% CI: 1.10, 7.59). In addition, maternal antibiotic use was a risk factor for prolonged/persistent diarrhea in these infants (HR: 1.63; 95% CI: 1.04, 2.55). Chapter 2: Among 372 HEU infants, mean LAZ decreased from -0.33 (standard deviation [SD]: 1.47) to -0.96 (SD: 1.23) between 0-12 months. Greater declines in LAZ were associated with household crowding and neonatal pneumonia, while higher maternal education and height were associated with greater gains in LAZ. Infants with low birthweight and birth stunting experienced some improvements in linear growth during infancy, with residual deficits at 12 months of age. Chapter 3: Diarrhea was associated an average loss of 0.07 (95% CI: -0.14, -0.00) in LAZ following the episode. More severe diarrhea (MSD) episodes were associated with greater declines in LAZ (adjusted difference [AD]: -0.18; 95% CI: -0.31, -0.06) compared to those without any diarrhea. Infants with any diarrhea (AD: -0.07 95% -0.16, 0.01) and MSD (AD: -0.22 95% -0.39, -0.04) not treated with antibiotics also experienced greater linear growth faltering than children with no diarrheal episodes and also no with antibiotics for any reason. Conclusions: HEU children are at risk for diarrhea and linear growth faltering and among these children, diarrhea contributes to linear growth faltering. In addition to improved community and nutritional support for these infants, interventions targeted at improving maternal health and education may decrease diarrhea and improve growth.
- Epidemiology