A blood sample taken from a newborn in Zimbabwe within hours of birth can reveal whether inflammation—driven by untreated maternal infections—is stunting their growth before they have even left the hospital. Low birth weight and preterm birth kill more than a million newborns each year, mostly in lower-income countries. In Zimbabwe, where sexually transmitted infections are common but often go untreated, the link between maternal infection, fetal inflammation, and poor birth outcomes is suspected but not understood at a molecular level. This study will analyse blood from 300 Zimbabwean newborns using protein assays and RNA sequencing, comparing those who develop sepsis, die, or are born underweight against healthy controls. If the research succeeds, it will identify specific inflammatory pathways and protein biomarkers that predict which babies are at risk. That could lead to a simple blood test for newborns in high-risk settings, enabling early intervention before damage is done. It could also strengthen the case for treating maternal STIs during pregnancy—not just to prevent transmission, but to protect fetal growth. The work is mechanistic, not yet a clinical tool, but it directly addresses a gap in knowledge that keeps neonatal mortality high in regions with limited resources.
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Low birth weight (LBW) and preterm birth remain significant contributors to neonatal mortality and long-term morbidity, particularly in lower- and middle-income countries (LMICs). Systemic inflammation during pregnancy is strongly linked to LBW and poor neonatal outcomes, yet the underlying mechanisms remain poorly understood. In Zimbabwe, where preterm birth rates are among the highest globally and sexually transmitted infections (STIs) are prevalent but often untreated unless symptomatic, maternal and neonatal inflammation may play a crucial role in child growth and birth outcomes. This study, a sub-study of the PROMISE trial, will investigate the hypothesis that neonatal inflammation, exacerbated by maternal STIs, reduces growth and leads to poorer outcomes. Blood samples from 300 neonates shortly after birth will be analysed using multiplex protein assays, while transcriptomic profiling will be performed on a case-control subset of those with neonatal sepsis or mortality by 6 weeks (n=30), LBW infants (n=30), and well-grown infants (n=30). RNA sequencing will identify differentially expressed genes and inflammatory pathways associated with LBW and poor outcomes. Findings will provide mechanistic insights into the role of inflammation in neonatal health and help identify biomarkers predictive of adverse outcomes. By integrating protein biomarker and transcriptomic analyses, this study will advance our understanding of neonatal immune responses and inform targeted STI interventions, or other testing to improve birth outcomes in high-risk populations. This research will contribute to the development of predictive tools for neonatal health, with potential applications in clinical screening and early intervention strategies.
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