Predicting preterm labor by combined testing of cytokines and cell-free DNA


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Abstract

Material and methods. The study comprised 80 patients, including 47 women with spontaneous preterm labor (study group) who were divided based on gestational ages as follows: 22-27weeks and 6 days (10), 28-33 weeks and 6 days (13) and 34-36 weeks and 6 days of gestation (24). Thirty-three women with normal pregnancies and full-term labor were enrolled in a control group. The levels total and fetal cell-free DNA in blood plasma was estimated by quantitative PCR by determining the concentration of the promoter of the RASSF1A gene and its hypermethylatedportion. The analysis included measurements of IL-2, IL-4, IL-6, IL-10, GM-CSF, IFNγ and TNFα concentrations using the multiplex method. The predictive value was determined by logistic regression. Results. Patients in the study group had increased levels of IL-6 at 22-27week and 6 days gestation, and in 60% (p = 0.003) of cases, there were signs of intrauterine infection. The level of IL-8 was significantly increased in the study group at 28-33 weeks and 6 days and 34-36 weeks and 6 days gestation. There were no differences between groups in the rates of intrauterine infection at 28-33 week and 6 days. In the study group, intrauterine infection was diagnosed in 37.5% of cases (p = 0.01) at 34-36 weeks and 6 days. The concentration of fetal cell-free DNA was increased at 28-33 week and 6 days gestation. The most predictive of preterm labor at 22-27 weeks and 6 days, 28-33 weeks and 6 days, and 34-36 weeks and 6 days was combined testing of IL-6 and cfDNA (AUC 0.925; 95% CI, 0.83-1), IL-8 and cffDNA (AUC 0.92; 95% CI, 0.85-1), and IL-8, cfDNA, and cffDNA (AUL 0.92; 95% CI, 0.85-1), respectively. Conclusion. Combined testing of cell-free DNA and cytokines is a promising approach for predicting preterm labor.

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About the authors

Aleksey M. Krasnyi

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

Email: alexred@list.ru
PhD, head of the cytology laboratory

Natalia E. Kan

National Medical Research Center for Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russian Federation

Email: n_kan@oparina4.ru
MD, professor, head of Department of Obstetric Observatory

Victor L. Tyutyunnik

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

Email: tioutiounnik@mail.ru
MD, head of the Obstetric Physiological Department

Alsu A. Sadekova

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

Email: a_sadekova@oparina4.ru
scientific researcher of the cytology laboratory

Alena G. Saribekova

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

Email: arushanovaa@mail.ru
the postgraduate student

Diana N. Kokoeva

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

Email: dikokoeva@mail.ru
the postgraduate student

Zalina Kh. Salpagarova

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

Email: z.salpagarovaI990@yandex.ru
the postgraduate student

Marzanat K. Medzhidova

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

Email: marzhana-m@yandex.ru
PhD candidate

Valentina V. Vtorushina

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

Email: v_vtorushina@oparina4.ru
PhD in medical sciences, doctor of laboratory diagnostics in Laboratory of Clinical Immunology

Lubov V. Krechetova

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

Email: l_krechetova@oparina4.ru
PhD the head of the immunology laboratory

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