Exhaled Breath Carbon Isotopes Are A Marker For Inflammation In Neonates With A Chorioamnionitis Risk Factor
Authors: Butz Daniel E , Pillers De‐Ann 
Published: November 2023

Chorioamnionitis is an inflammatory response of the chorioamnion (i.e. fetal membranes) related to infection. Chorioamnionitis is a leading cause of premature rupture of membranes and of premature birth. Although only 3 to 10% of neonates develop congenital sepsis from confirmed cases of chorioamnionitis, empiric antibiotic treatment is initiated as a precautionary measure in all chorioamnionitis cases. Antibiotic treatment continues for 48–72 hours while infants are evaluated and cultures grown to confirm the presence or absence of infection. During this time, the infant may be isolated from the mother while they are in the neonatal intensive care unit for antibiotic treatment. Thus up to three days of unnecessary treatment and isolation occurs in almost 97% of cases, at a significant cost to the healthcare system. Furthermore, there are untold human costs associated with separation of the neonate from their mother, including compromise of maternal‐infant bonding, disruption of breastfeeding, and uncertainty and stress for the parent.

We have recently demonstrated that the exhaled breath delta value (BDV or 13CO2/12CO2 ratio) is a marker of the acute phase response to infection in critically ill subjects.

The objective of this study was to evaluate the BDV as a marker for early onset sepsis in neonates born to mothers with a chorioamnionitis risk factor. Expecting mothers were screened for clinical chorioamnionitis. Eligible neonates were enrolled in the study as soon after birth as practical. Breath samples were obtained via nasal cannula and samples were collected in aluminized breath sample bags. Breath samples were collected at enrollment and every 8 hours thereafter for up to 72 hours. The BDV was determined by Isomark, LLC using the Canary™ breath monitor, a medical device being developed for determining the exhaled breath carbon isotope ratio. Information relating to inflammation and infection was abstracted from the medical record. In addition to demographic data and placental pathology, we collected white blood cell count, body temperature, heart rate, respiratory rate, blood pressure, blood oxygen saturation, absolute neutrophil count, C‐reactive protein, immature to total neutrophil ratio and infection status. We separated the subjects by the number of inflammation parameters that were outside of the reference range for age and correlated the severity of inflammation to the BDV over time. Mean trend in BDV during the first three days of life for neonates with zero or one inflammation criteria was flat while subjects with two or more inflammation criteria had a trend with a negative slope. While none of the subjects developed an overt infection during our study due to empiric antibiotic treatment, our data demonstrates that the BDV correlates with the level of systemic inflammation. These data suggest that BDV could serve as a decision‐support tool for determining whether continued antibiotic use is needed beyond the prophylactic “sepsis rule‐out” period.

Support or Funding Information

NIH ‐ EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

Title: A new smart neonatal incubator for real‐time detection of sepsis

Award ID: R43HD072926