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The SPITSS study

09/06/2019

Jill Maron, MD, MPH is a neonatologist at Floating Hospital for Children.Dr. Jill Maron, Executive Director of MIRI, has been awarded $3.6 million from the NICHD for a five-year multi-site grant entitled “Salivary Profiling in Infants Treated for Suspected Sepsis: The SPITSS Study.” Dr. Maron, whose expertise is salivary diagnostics, will oversee the 4,000 subject study, which also includes Women & Infants Hospital, Rhode Island, the University of Florida, Gainesville, and Brigham and Women’s Hospital, Boston.

The study will test the first comprehensive sepsis-screening platform developed for neonatal care. It will evaluate whether repeated analyses of neonatal saliva for cytokines (biomarkers of infection) could provide a more rapid manner of diagnosing sepsis and other infections in newborns.

Reduced infant exposure to antibiotics for newborns

Infection accounts for nearly 24% of neonatal mortality worldwide. Premature infants are especially at risk for infections since their immune systems are immature. The most severe form of infection can lead to sepsis, a serious condition with multi-end organ failure, cardiovascular instability, and an exaggerated systemic inflammatory response.  Premature neonatal sepsis survivors have greater risk of impaired growth, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and prolonged hospitalizations. They also suffer from damage to brain structure with poorer neurodevelopmental outcomes and a higher incidence of cerebral palsy.  

In order to rule out the possibility that an infant has sepsis, a ROS (rule out sepsis) test is commonly performed on infants whose symptoms are similar to those of sepsis, and the infant receives antibiotics during the ROS test. While it is important to start an infected infant on antibiotics as quickly as possible, caregivers struggle to correctly identify which infants are truly infected, since both infected and uninfected newborns can exhibit identical symptoms, such as apnea (forgetting to breathe), jaundice, and temperature instability.  

Furthermore, the prescription of antibiotics in itself, once thought benign and prophylactic, has been shown to cause susceptibilities to other conditions, such as side effects from the antibiotics themselves, development of a resistant strain of bacteria, and an increased risk of mortality.  Hence, doctors must strike a delicate balance in prescribing antibiotics to infants who exhibit signs of infection and those who exhibit signs of prematurity. Thus the fundamental aim and importance of the study is reducing the amount of time a newborn is receiving antiobiotics during a ROS test.  

About the study

Samples of saliva will be taken from a total of 4,000 newborns: 1,300 from Tufts Medical Center; 1,450 from Women & Infants Hospital in Rhode Island (site PI Joseph Bliss, MD, PhD); and 2,250 from the University of Florida in Gainesville (site PI James Wynn, MD). The samples will be taken when subjects begin antibiotics for a ROS, and 18-36 hours later. The saliva samples will then be shipped to Dr. David Walt’s laboratory at the Brigham and Women’s Hospital for cytokine analysis. Statistical analyses of these biomarkers will confirm sepsis, other types of infection, or lack of infection.  

Potential benefits of the study

The method being tested, if successful, could have several other benefits besides reducing antibiotic exposure in newborns. Hospitalizations could be shortened, saving tens of millions of dollars.  If successful, this approach may also allow doctors to better differentiate bacterial from viral infections, and more quickly prescribe the proper drugs to treat them.  For premature infants, their saliva profiles may help determine risk for other conditions associated with prematurity and inflammation, including lung and eye disease.