Salivary Diagnostics for Sepsis Screening in the Neonate

Infection is a leading cause of mortality in the newborn and confers substantial life-long morbidities to survivors including deleterious changes in brain structure, worse neurodevelopmental outcomes, and a higher incidence of cerebral palsy. Early clinical symptoms of infection are subtle, nonspecific, or mirror symptoms commonly seen in the uninfected premature newborn, including difficulty breathing, jaundice, and temperature instability. For this reason, ‘rule out sepsis’ is one of the most common diagnostic tests in neonatal intensive care units. Existing testing requires culturing the infection from a blood draw that potentially negatively affects neurodevelopment and exaggerates anemia in the fragile premature infant. There is an urgent need to better discriminate between infected and uninfected newborns to provide timely treatment.

The goal of this research is to validate the first non-invasive test to quantify multiple inflammatory biomarkers in neonatal saliva from serial time points. This test aims to improve infection-screening accuracy and reduce unwarranted antibiotic exposure in the newborn. Biomarker quantification from saliva not only eliminates painful stimuli and blood loss, but also provides a safe alternative for the quantification of protein signatures of disease in the newborn. The Walt Lab has optimized salivary biomarker assays to successfully quantify inflammatory host response biomarkers in neonatal saliva. In a prospective, observational trial, with training and validation cohorts, the Walt Lab paired with international experts in neonatal infection and immune response to develop and validate a predictive model of neonatal sepsis. Co-Investigators include Dr. Jill Maron (Women and Infants’ Hospital), Dr. James Wynn (University of Florida, Gainesville), Dr. Elizabeth Yen (Tufts Medical Center), and Dr. Joseph Bliss (Women and Infants’ Hospital).  These samples have been banked and will be available to enable the quantification of additional biomarkers to predict other neonatal morbidities. The completion of this study will enhance the accuracy of sepsis screening, reduce unwarranted antibiotic therapy, and significantly improve neonatal care and outcomes.

Funding: National Institutes of Health (PA-18-484).