New Biomarker: iAP Accurately Diagnoses Deadly Infant Disease Called NEC (Necrotizing Enterocolitis).
Researchers and clinicians at LSU Health New Orleans School of Medicine have discovered a new biomarker, a protein called iAP
for the noninvasive detection of necrotizing enterocolitis
) that only mostly affects infants. The diagnostic study was one of the largest prospective clinical studies in premature infants yet, involved 136 premature infants.
is a life-threatening illness almost exclusively affecting neonates. NEC
has a mortality rate as high as 50%. Inflammation of the intestine leads to bacterial invasion causing cellular damage and cell death, which causes necrosis of the colon and intestine. As NEC
progresses, it can lead to intestinal perforation causing peritonitis, sepsis and death. To date, no clinical test has been established as the gold standard to diagnose NEC. X-rays are used to diagnose advanced disease, but their sensitivity can be as low as 44%.
Dr Sunyoung Kim, Ph.D., Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine and senior author told Thailand Medical
News, "This study exemplified academic medicine at its best. It creates linkages between unexplained patient presentations and scientific inquiry. We were driven by the desire to build unique and useable tools to fight a disease that has been unexplained for nearly 200 years in the most fragile patient population, preemie babies."
Past research suggested that NEC
is preceded and accompanied by changes in the complex and dynamic collection of microorganisms called gut microbiota, which live in the intestine. In this study, the research team measured and analyzed the activity of the protein, intestinal alkaline phosphatase (iAP
) obtained from stool samples from the babies enrolled in the study at Children's Hospital of New Orleans, Touro Infirmary, and St. Louis Children's Hospital. Clinical data collected included gestational age, birth weight, Apgar scores, delivery type, race, gender, feeding, antibiotics, laboratory and radiology results, as well as surgical notes. Eighteen percent of the babies were classified as having severe NEC
; 14% had suspected NEC
; and 68% were NEC
activity precedes the chemical process triggering inflammation, the researchers studied the abundance and enzyme activity of iAP
shed in stool to assess the correlation of two iAP
biochemical measures with disease severity. They found that elevated levels of iAP
protein linked to NEC
were shed in the samples, but the proteins were dysfunctional in the NEC patients. The accuracy rates using iAP
levels and iAP
activity as markers for severe NEC
were 97% and 76%, respectively. The accuracy values were similar for suspected NEC
,97% and 62%, respectively.
These findings indicate that iAP
biochemistry and abundance can be used as diagnostic biomarkers for both severe and suspected NEC
strong>. Significantly, iAP measures were not biomarkers for sepsis, another potentially fatal condition that can exhibit symptoms similar to NEC. A correct diagnosis is crucial to treatment decisions.
The new biomarker has doubled the diagnostic identification of the disease, compared to the current gold standard a milestone important at both the bench and the bedside.
Dr. Kim further added "Intestinal AP is the first candidate diagnostic biomarker, unique in its predictive value for NEC. It is correlated only with NEC and is not associated with sepsis or other non-GI infections. The clinical potential of this noninvasive tool lies in its use to identify infants most at risk to develop NEC, to facilitate management of feeding and antibiotic regimens, and monitor response to treatment.”
The team is planning more clinical studies before submitting it to regulatory bodies and medical councils to adopt the new biomarker as a to be adopted standard diagnostic platform for NEC in infants.
Reference: JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.14996