Project Details

The role of maternal STI interventions on infant inflammation, growth, and outcomes in Zimbabwe

Jonathan Sturgeon, MBBS, MA, PhD, DMCC, DTM&H

Summary

BACKGROUND: Low birth weight (LBW, < 2500g) and preterm birth (< 37 weeks’ gestation) are significant contributors to neonatal mortality and long-term morbidity. Inflammation during pregnancy is strongly associated with LBW and poorer neonatal outcomes, likely through changes in the inflammation-growth factor axis, yet the causal inflammatory mechanism is poorly understood. It is likely exacerbated by chronic infections such as sexually transmitted infections (STIs), which in many settings are only treated if the mother has symptoms, missing 90% of these infections. Zimbabwe, with the fourth-highest global preterm birth rate and a high 20% prevalence of untreated maternal STIs, presents a unique setting to explore this interaction, and provide deeper evidence on the effect of increased STI testing and treatment in pregnancy. GAP: The role of maternal STIs in driving higher chronic inflammation in the baby in a high-burden setting is unknown. HYPOTHESIS: Untreated STIs in pregnancy will result in higher neonatal exposure to chronic inflammation, decreasing birthweight and subsequent growth, and increase the risk of neonatal sepsis and death. Aim 1: Examine the impact of randomized maternal STI testing/treatment on neonatal inflammatory and growth biomarkers at birth Aim 2: Examine transcriptomic signatures to elucidate the upstream causative pathways of the inflammation in those with higher inflammation, correlating expression with presence of STIs Aim 3: Examine the association of increased inflammation with growth and/or poorer outcomes METHODS: This will be a sub-study of the PROMISE trial, an MRC-funded randomized interventional study examining the benefits of additional STI screening in pregnancy. It is being run in 15 antenatal clinics in Harare, Zimbabwe. It will recruit 150 babies from the standard-of-care arm with symptomatic STI treatment only (missing ~90% of infections), and 150 babies in the intervention arm with extra testing for chlamydia, gonorrhoea, and trichomonas. Blood from babies taken shortly after birth will be analyzed for a multiplex suite of 25 biomarkers covering systemic and vascular inflammation, and growth factors. A subset (n=50) will undergo transcriptomic analysis, finding the inflammatory pathways. Primary outcomes are biomarker concentrations, growth by 6 weeks, and neonatal death or admission with sepsis in this time. RESULTS: Pending. IMPACT: This study could provide critical insights into the role of untreated maternal STIs in driving neonatal inflammation, offering downstream evidence to support policies of comprehensive STI screening. By elucidating the inflammatory pathways involved, the findings could also inform targeted therapeutics to enhance infant growth/survival after STI treatment. Website Link: https://www.imperial.ac.uk/people/j.sturgeon