# Molecular Signatures of Early-Onset Neonatal Sepsis in Umbilical Cord Blood

> **NIH NIH K23** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2021 · $189,432

## Abstract

PROJECT SUMMARY
Early-onset sepsis (EOS) due to invasive bacterial infection is a leading cause of morbidity in infants and
disproportionately affects those born preterm. Accurate diagnosis of EOS remains inadequate. The low
sensitivity and delayed time to culture results combined with the poor predictive values of available laboratory
markers leads to our inability to rule-out EOS. Thus, infants are exposed to extended duration broad-spectrum
empiric antibiotics, which have serious associated adverse consequences such as necrotizing enterocolitis,
antibiotic resistant infections, and an altered microbiome. The proposed research will apply proteomics to identify
gestational age-specific umbilical cord blood markers toward development of a proposed diagnostic tool with
strong negative risk prediction for EOS. Cord blood is promising to identify EOS as it reflects the intrauterine
environment where infection originates in preterm birth. In previous work, we found that inflammatory proteins
serum amyloid A, C-reactive protein and haptoglobin are substantially elevated in cord blood of preterm infants
with culture-confirmed EOS. These data inform our hypothesis that a combination of cord blood proteins provides
a signature to differentiate impending EOS and uninfected states. Archived cord blood from infants in an existing
longitudinal cohort will be used in a nested case-control design. Aim 1 will measure the cord blood proteome of
uninfected infants (controls) across gestational ages using an untargeted proteomics approach to characterize
the developmental spectrum. Aim 2(a) will then determine the cord blood proteome signatures of infants with
confirmed EOS (cEOS) and culture-negative presumed sepsis (PS). cEOS will be compared to matched controls
to identify differentially expressed proteins and candidate markers. PS proteomes will be analyzed to help
delineate true infection versus inflammatory subtypes in this heterogeneous group. Bioinformatics pathway
analysis may provide novel insights into fetal immune response. Aim 2(b) will determine the best combination of
markers to exclude EOS through machine learning decision analysis of proteomics data. Paired placental
proteomics in Aim 2(c) will explore origins of fetal inflammation. Aim 3(a) will quantify candidate proteins by an
orthogonal immunoassay method. In a validation set of new subjects, Aim 3(b) will measure candidate markers
by targeted proteomics and test application of the proposed diagnostic tool. With formal didactics and a
mentorship team at Northwestern University with expertise in prematurity, sepsis, biomarker discovery,
biostatistics, and decision modeling led by Patrick Seed MD Ph.D., the candidate will gain advanced translational
research experience and skills in perinatal research study design, advanced immunology, proteomics, and
bioinformatics to further her research agenda. The proposed research and career development will be
fundamental towards achieving the candidate’s ...

## Key facts

- **NIH application ID:** 10086375
- **Project number:** 5K23AI139337-03
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Leena Bhattacharya Mithal
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,432
- **Award type:** 5
- **Project period:** 2019-02-04 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086375

## Citation

> US National Institutes of Health, RePORTER application 10086375, Molecular Signatures of Early-Onset Neonatal Sepsis in Umbilical Cord Blood (5K23AI139337-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086375. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*