Congenital Infections as Risk Factor For Adverse Birth Outcomes Among HIV-Exposed Neonates in Uganda

Prematurity and low birth weight (LBW) are leading risk factors for morbidity among HIV-exposed uninfected (HEU) neonates. The IMPAACT PROMISE 1077BF trial found high rates of adverse pregnancy outcomes among women living with HIV (WLHIV) randomized to triple antiretroviral treatment compared to zidovudine alone. We sought to elucidate the possible association of select congenital infections with preterm delivery (PTD) and low birth weight (LBW) among Women Living with HIV (WLHIV) on ART.

This study was designed as 1:2 nested case-control study of Ugandan mother/infant pairs enrolled in the IMPAACT 1077BF trial. All eligible mother/infant pairs with a PTD (< 37 weeks) or LBW (<2500 gm) HIV Exposed Uninfected (HEU) infants were selected as cases. For every case, up to two control maternal-infant pairs of similar maternal age, parity, and infant specimen availability were selected.PCR testing for cytomegalovirus (CMV) and syphilis testing (RPR and Treponema test if RPR positive) were done for all maternal samples at delivery. Infant testing was performed if the maternal sample was positive. Weighted estimates of prevalence were calculated for each congenital infection. Multivariable weighted modified Poisson models were fit to assess the association between maternal congenital infections and adverse pregnancy outcomes.

Among 158 women, the estimated prevalence (95% CI) of syphilis or CMV was 49% (39%, 58%). Prevalence estimates for maternal CMV and syphilis were 44% and 7%, respectively. Infant prevalence estimates were 7% for CMV and 2% for syphilis. CMV was associated with a significantly increased risk of PTD and/or LBW; Risk Ratio (95% CI): 2.2 (1.2, 4.1).

This study found a high burden of congenital infections among women with HIV, and maternal CMV was associated with increased risk of PTD and/or LBW. Further evidence is needed on feasibility and clinical benefit of CMV screening for HEU infants in high-burden settings.