Growth patterns and their contributing factors among HIV‐exposed uninfected infants

Abstract

With expanded HIV treatment and prevention programmes, most infants born to HIV-positive women are uninfected, but the patterns and determinants of their growth are not well described. This study aimed to assess growth patterns in a cohort of HIV-exposed uninfected (HEU) infants who participated in an experimental HIV vaccine trial and to test for associations with maternal and infant factors, including in-utero exposure to antiretroviral therapy (ART), mode of delivery, exclusive breastfeeding, mother's education and receipt of the vaccine. Infants in the trial were seen at regular clinic visits from birth to 48 weeks of age. From the anthropometric measurements at these visits, weight-forage z-scores (WAZ), weight-for-length zscores (WLZ) and length-forage z-scores (LAZ) were computed using World Health Organization (WHO) software and reference tables. Growth patterns were investigated with respect to maternal and infant factors, using linear mixed regression models. From 94 infants included at birth, growth data were available for 75.5% at 48 weeks. The determinants of infant growth in this population are multifactorial: infant LAZ during the first year was significantly lower among infants delivered by caesarean section (p = 0.043); both WAZ and LAZ were depressed among infants with longer exposure to maternal ART (WAZ: p = 0.015; LAZ: p < 0.0001) and among infants of mothers with lower educational level (WAZ: p = 0.038; LAZ: p < 0.0001); the effect of maternal education was modified by breastfeeding practice, with no differences seen in exclusively breastfed infants. These findings inform intervention strategies to preserve growth in this vulnerable infant population.

No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi

“…Our data highlight that CHEU repeatedly presented with lower WAZ and LAZ than the reference population, with some evidence of early catch-up growth from enrollment to visit 1, although not prolonged as z-scores declined by visit 2. Our findings approximate those of previous Eastern and Southern African studies ( 10 – 15 , 17 , 21 ), including a large cohort of South African CHEU, where ART coverage in pregnancy was estimated at 96–97% (2013–2016) ( 37 ) and CHEU presented with negative LAZ between the ages of 6 weeks and 12 months, with some recovery between 6 weeks and 3 months of age ( 10 ). Consistent with our findings, several studies [conducted when antenatal ART coverage was estimated at 85–90% in Eastern and Southern Africa ( 37 )] have reported a decline in WAZ or LAZ in CHEU starting as early as the age of 3 months and often between the ages of 6 and 9 months, around the time of introduction to complementary foods ( 10 , 11 , 17 , 20 ).…”

“…CHEU in resource-limited settings experience complex and multifactorial exposures ( 9 ), including maternal ill health, increased risk of infectious disease, poverty, and poor nutrition. Whether in utero and early life exposures to HIV and ART have the potential to adversely affect the fetal and postnatal growth independently of other factors is unclear, although there is growing evidence suggesting that this is the case for CHEU ( 10 – 17 ).…”

“…Recently, findings from the PROMISE trial in Malawi and Uganda demonstrated that maternal HIV and ART were associated with lower length-for-age z-scores (LAZ) and weight-for-age z-scores (WAZ), and that CHEU were more likely to be stunted at Up to 24 months of age than CHU ( 15 ). Evidence on the effect of timing of ART exposure on growth is inconsistent ( 17 – 22 ); some studies have reported poorer growth in CHEU exposed to ART from conception compared with that of later, while others have noted no difference.…”

Relationship between pre‐pregnancy maternal body mass index and infant weight trajectories in HIV‐exposed and HIV‐unexposed infants

“…18 Impaired growth has been reported among CEUH, relative to CUH, in other sub-Saharan African cohorts. [50][51][52] However, in this cohort high levels of overweight and rapid weight gain were observed and did not differ by HIV exposure status. In the South African context, high levels of maternal obesity and relatively short duration of breastfeeding may in part explain the high prevalence of overweight and rapid weight gain observed in infants.…”

“…For infants exposed to HIV and ART in utero, the mechanisms by which HIV and ART exposure may influence growth and metabolic health are not well understood but may be related to mitochondrial toxicity or placental insufficiency 18 . Impaired growth has been reported among CEUH, relative to CUH, in other sub‐Saharan African cohorts 50–52 . However, in this cohort high levels of overweight and rapid weight gain were observed and did not differ by HIV exposure status.…”