Amino acid profile of umbilical cord blood plasma of premature newborns in early diagnosis of necrotizing enterocolitis: a pilot study

BACKGROUND: Necrotizing enterocolitis is a common emergency condition in premature infants, which is characterized by high rates of mortality and disability. Its diagnosis is complex and often ineffective, thus, the search for biomarkers for prognosis and early diagnosis of the disease is underway.

AIM: To identify changes in the amino acid spectrum of umbilical cord blood plasma that precede the development of necrotizing enterocolitis in extremely premature infants.

MATERIALS AND METHODS: The study was conducted from June 2023 to May 2024. Umbilical cord blood was obtained from physiological and operative deliveries of extremely preterm newborns of ≤32 weeks gestational age, considering the informed consent obtained from the mother, absence of standard contraindications, and exclusion criteria. The children were observed from birth to discharge. Necrotizing enterocolitis was diagnosed by identifying laboratory signs of a systemic inflammatory response in combination with clinical and instrumental data. Amino acid levels in cord blood plasma were determined by capillary electrophoresis. Based on the results of monitoring patients, two groups were retrospectively formed: the comparison group including 10 extremely premature newborns who did not develop necrotizing enterocolitis during the entire observation period, and the main group consisting of 5 patients with necrotizing enterocolitis. The study participants were comparable in body weight and Apgar and Ballard scores at birth. In the main group, necrotizing enterocolitis of stages I–III was diagnosed within 2 weeks of birth.

RESULTS: The development of necrotizing enterocolitis is preceded by a decrease in proteinogenic amino acid level in the umbilical cord blood plasma by 13.9% (p=0.019). This includes the levels of arginine and proline (by 36.2 and 32.8%, p=0.008 and p=0.028, respectively), leucine and isoleucine (41.8 and 36.9%, p=0.030 and p=0.005, respectively), and tryptophan (by 35.5%, p=0.019). A decrease in the levels of methionine (by 28.0%, p=0.028), serine (by 24.1%, p=0.013), and phenylalanine (by 15.8%, p=0.040) was less pronounced, but statistically significant.

CONCLUSION: Comparing the data obtained to the results of other studies, disturbances in the biosynthesis and/or transplacental transfer of amino acids (primarily arginine and amino acids with branched hydrocarbon radicals) can be considered as crucial links in the pathogenesis of necrotizing enterocolitis. The present study used umbilical cord blood obtained at the birth of a child, hence, the identified changes should be considered not as a consequence of intestinal damage but as specific changes in the pool of free amino acids, against which necrotizing enterocolitis is highly possible to develop.