Genetic predictors of necrotizing enterocolitis in neonates


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Abstract

Aim. To reveal molecular genetic predictors of necrotizing enterocolitis (NEC) in preterm neonates. Materials and methods. The study included 590 neonates (gestational age (GA) 24-41 weeks) admitted to the Neonatal Intensive Care Unit during the first hours of life from January 2015 to December 2017. All neonates underwent sampling of biological material (venous blood and buccal swabs) before the start of medical treatment and enteral feeding. The reverse transcription method was used to measure gene expression levels: IL1b, IL6, IL8, IL10, К12а, IL15, IL18, TNFa, TGFb1, TBX21, GATA3, RORC2, CD45, CD68, CD69, TLR2, TLR4, TLR9 and MMP8. We compared gene expression in venous blood and buccal swabs of neonates who developed NEC and those without NEC. Results. The development of NEC was noted in 25 out of590 newborns initially included in the study (4.2%). After the technical assessment of biomaterial and exclusion of 172 newborns, there were remaining 418 patients with 18 cases of NEC. After statistical adjustment according to GA there were 130 patients remaining: 16 neonates with NEC and 114 patients in control group (without NEC). In premature infants, a statistically significant increase in the level of expression of the TLR4 in blood was associated with the development of NEC. The study also revealed a downward trend in GATA3 in neonates with NEC compared with the control group. The decimal Lg (TLR4/GATA3) then was calculated and ROC analysis showed decent prognostic value of this criterion. Threshold value of 0.74, the sensitivity of the model - 88%, and the specificity - 77%; positive predictive value (PPV) - 39%, negative predictive value (NPV) - 97%. The same analysis in the buccal epithelium didn’t show significant differences between the groups. The expression level of other genes did not differ statistically significantly between groups. Conclusion. The determination of the TLR4 gene expression in very premature infants born on 24-32 weeks of gestation can be used as a predictor of necrotizing enterocolitis.

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About the authors

Irina V. Nikitina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: i_nikitina@oparina4.ru
MD, Ph.D., Leading Researcher of the Neonatal Intensive Care Unit №2 of the Institute of neonatology and pediatrics

Andrey E. Donnikov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_donnikov@oparina4.ru
M.D., Ph.D., Head of laboratory of molecular genetic methods

Olga A. Krogh-Jensen

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: olgaborisevich@gmail.com
M.D., Ph.D., neonatologist of the Neonatal Intensive Care Unit No. 2 of the Institute of Neonatology and Pediatrics

Regina V. Krasheninnikova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: r_krasheninnikova@oparina4.ru
MD, Geneticist of laboratory of molecular genetic methods

Oksana S. Nepsha

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_nepsha@oparina4.ru
Ph.D., Researcher of the Institute of Reproductive Medicine

Anna A. Lenyushkina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a-lenushkina@yandex.ru
MD, Ph.D., Head of the Neonatal Intensive Care Unit №2 of the Institute of neonatology and pediatrics, Associate Professor of Neonatology Department

Dmitriy N. Degtyarev

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: d_degtiarev@oparina4.ru
MD, PhD, Vice director of Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Professor of Neonatology Department, Professor, Head of neonatal department at Pediatric Faculty

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