Preterm birth and severe morbidity in hospitalized neonates who are HIV exposed and uninfected compared with HIV unexposed

Abstract

Objectives: Infants who are HIV exposed but uninfected (HEU) compared with HIV unexposed uninfected (HUU) have an increased risk of adverse birth outcomes, morbidity and hospitalization. In the era of universal maternal antiretroviral treatment, there are few insights into patterns of neonatal morbidity specifically.Design: A prospective cohort study. Methods:We compared neonatal hospitalizations among infants who were HEU (n ¼ 463) vs. HUU (n ¼ 466) born between 2017 and 2019 to a cohort of pregnant women from a large antenatal clinic in South Africa. We examined maternal and infant factors associated with hospitalization using logistic regression.Results: Hospitalization rates were similar between neonates who were HEU and HUU (13 vs. 16%; P ¼ 0.25). Overall, most hospitalizations occurred directly after birth (87%); infection-related causes were identified in 34%. The most common reason for hospitalization unrelated to infection was respiratory distress (25%). Very preterm birth (<32 weeks) (29 vs. 11%; P ¼ 0.01) as well as very low birthweight (<1500 g) (34 vs. 16%; P ¼ 0.02) occurred more frequently among hospitalized neonates who were HEU. Of those hospitalized, risk of intensive care unit (ICU) admission was higher in neonates who were HEU (53%) than HUU (27%) [risk ratio ¼ 2.1; 95% confidence interval (95% CI) 1.3-3.3]. Adjusted for very preterm birth, the risk of ICU admission remained higher among neonates who were HEU (aRR ¼ 1.8; 95% CI 1.1-2.9). Conclusion:Neonates who were HEU (vs. HUU) did not have increased all-cause or infection-related hospitalization. However, very preterm birth, very low birthweight and ICU admission were more likely in hospitalized neonates who were HEU, indicating increased severity of neonatal morbidity.

Increased infectious-cause hospitalization among infants who are HIV-exposed uninfected compared with HIV-unexposed

“…Among women with available data, 88% had viral load less than 400 copies/ml at the measurement closest to delivery and mean CD4 þ cell count was 488 cells/ml (95% CI 466-511). The maternal cohort was previously described [29].…”

“…Much of the existing evidence of infectious morbidity in infants HEU predates the era of universal maternal ART. We previously found similar allcause and infection-related hospitalization rates in a cohort of neonates HEU vs. HUU, although hospitalized neonates HEU had increased risk of very preterm birth, very low birthweight, and intensive care admission [29]. In this additional analysis of the cohort, we describe hospitalization patterns in the postneonatal period until 1 year of age and we examine maternal and infant factors associated with infectious-cause hospitalization.…”

It is a question of equity: time to talk about children who are HIV‐exposed and “HIV‐free”

“…However, we do know that maternal ART has not resolved the issue and that being born with one of these adverse birth outcomes and to a woman living with HIV multiplicatively impacts further on child outcomes even in the absence of vertical HIV acquisition. Compared to children who are HIV‐unexposed born preterm, those who are HIV‐exposed and HIV‐free born preterm experience higher rates of neonatal mortality, require neonatal intensive care twice as often and experience worse infant cognitive and motor developmental outcomes [9–11]. Similarly, infants who are HIV‐exposed with foetal growth restriction do not catch up their growth deficits during the first year of life as children who are HIV‐unexposed with foetal growth restriction do [12].…”

Host-Viral Interactions at the Maternal-Fetal Interface. What We Know and What We Need to Know

“…A number of investigators have noted that even when MTCT of HIV-1 is prevented, HIV-1-exposed infants and children (HEU) exhibit impaired immunity in postnatal life associated with adverse clinical outcomes compared with HIV-unexposed/-uninfected (HUU) children. Most infection-related hospitalizations are associated with bloodstream or respiratory infections ( 17 , 42 , 43 ). HCMV infection in HIV-1-infected pregnant women was shown to alter fetal immune responses even in the absence of MTCT of HIV-1 ( 44 ).…”