Maternal Determinants Of Fetal Growth, Pregnancy Outcomes, And Early Childhood Growth And Development Among Hiv-Exposed And Hiv-Unexposed Infants

Abstract

Maternal HIV infection during pregnancy is associated with increased risk of adverse obstetric and infant outcomes, and understanding the factors responsible for this association is essential for designing effective interventions. Maternal malnutrition is an important determinant of maternal and infant health for both HIV-infected and - uninfected women. However, the relative contributions of food insecurity and infectioninduced changes in appetite and body weight regulation that alone, or in combination, contribute to malnutrition among HIV-infected women is largely unknown. The goal of this research was to advance the understanding of the underlying mechanisms by which maternal HIV infection influences pregnancy and early childhood outcomes. A prospective cohort of 114 pregnant women of mixed HIV-status was established in northwestern Tanzania. Pregnant women were followed through delivery and mother-infant dyads participated in follow-up visits at 1, 2, 3 and 6 months postpartum. This study had three main research aims: (1) to investigate maternal HIV and maternal anthropometric indicators as potential determinants of infant outcomes, (2) to characterize maternal and umbilical cord blood cytokine profiles and relate these to infant outcomes, and (3) to evaluate maternal cachexia characteristics during pregnancy. Maternal HIV status and maternal gestational mid-upper arm circumference (MUAC) were compared to infant anthropometric measurements from birth to six months of age. Infants born to HIV-infected mothers weighed, on average, 235 g less and were 1 cm shorter at birth compared to those born to HIV-uninfected mothers. Among mothers of mixed HIV-status, infants born to women with low MUAC had lower birth length and head circumference than infants born to women with higher MUAC. Maternal HIVinfection and low MUAC were also associated with poorer infant growth indicators through six months postpartum. Examination of cytokine profiles during pregnancy in this cohort revealed that HIV-infected pregnant women experienced elevated tumor necrosis factor (TNF)-[alpha]inflammation compared to HIV-uninfected pregnant women. On average, TNF-[alpha] concentrations were 14% higher among HIV-infected pregnant women. Among HIVinfected women, longer duration of antiretroviral therapy and more aggressive antiretroviral therapy were associated with more favorable cytokine profiles. Umbilical cord blood cytokine concentrations were used as a proxy for intrauterine exposure. Elevated umbilical cord blood cytokine concentrations were associated with lower infant birth weight and length. Pregnant women were also evaluated based on biopsychosocial characteristics related to cachexia. Based on a modified cachexia scoring system, HIV-infected and HIV-uninfected pregnant women had comparable cachexia symptoms. Evidence of increased gestational cachexia was associated with less favorable infant birth anthropometrics; and, among HIV-infected mothers, cachexia score was associated with lower infant weight-for-age and length-for-age z-scores at six months of age. These results provide evidence that maternal and fetal inflammation, and secondary biopsychosocial consequences, may have important implications for early childhood growth. Evaluated together, the findings of this dissertation research suggest that maternal HIV, immune abnormalities and undernutrition during pregnancy are important determinants of infant outcomes in rural and semi-rural Tanzania, and are interrelated. Understanding the relationships between maternal infections, nutrition and infant outcomes may be essential for designing successful interventions to improve infant health and growth outcomes in this context.