akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2024.546akusherstvo-2287Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИThe relationship between clinical-anamnestic data and cell-free fetal DNA level assessed by semiconductor sequencing within non-invasive prenatal testingВзаимосвязь клинико-анамнестических данных и уровня внеклеточной фетальной ДНК, определенного в рамках неинвазивного пренатального скрининга с помощью полупроводникого секвенированияhttps://orcid.org/0000-0002-6996-8891ВашуковаЕ. С.VashukovaE. S.

Вашукова Елена Сергеевна, к.б.н.

199034 Санкт-Петербург, Менделеевская линия, д. 3

Elena S. Vashukova, MD, PhD in Biology

3 Mendeleevskaya Liniya, Saint Petersburg 199034

vi_lena@list.ruhttps://orcid.org/0000-0003-3394-7391ТарасенкоО. А.TarasenkoO. A.

 Тарасенко Ольга Александровна, к.б.н.

199034 Санкт-Петербург, Менделеевская линия, д. 3

Olga A. Tarasenko, MD, PhD in Biology

3 Mendeleevskaya Liniya, Saint Petersburg 199034

https://orcid.org/0000-0002-5647-6783МальцеваА. Р.MaltsevaA. R.

 Мальцева Анастасия Романовна 

199034 Санкт-Петербург, Менделеевская линия, д. 3

Anastasiya R. Maltseva, MD.

3 Mendeleevskaya Liniya, Saint Petersburg 199034

https://orcid.org/0009-0008-3512-2557ПоповаА. К.PopovaA. K.

Попова Анастасия Константиновна

199034 Санкт-Петербург, Менделеевская линия, д. 3

Anastasiia K. Popova, MD. 

3 Mendeleevskaya Liniya, Saint Petersburg 199034

https://orcid.org/0000-0003-4116-0222ПачулияО. В.PachuliiaO. V.

Пачулия Ольга Владимировна, к.м.н.

199034 Санкт-Петербург, Менделеевская линия, д. 3

Olga V. Pachuliia, MD, PhD.

3 Mendeleevskaya Liniya, Saint Petersburg 199034

https://orcid.org/0000-0002-6542-5953БеспаловаО. Н.BespalovaO. N.

Беспалова Олеся Николаевна, д.м.н. 

199034 Санкт-Петербург, Менделеевская линия, д. 3

Olesya N. Bespalova, MD, Dr Sci Med.

3 Mendeleevskaya Liniya, Saint Petersburg 199034

https://orcid.org/0000-0002-7465-4504ГлотовА. С.GlotovA. S.

Глотов Андрей Сергеевич, д.б.н. 

199034 Санкт-Петербург, Менделеевская линия, д. 3

Andrey S. Glotov, MD, Dr Sci Biol. 

3 Mendeleevskaya Liniya, Saint Petersburg 199034

ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияOtt Research Institute of Obstetrics, Gynecology and ReproductologyRussian Federation202410012025186820834Copyright © Vashukova E.S., Tarasenko O.A., Maltseva A.R., Popova A.K., Pachuliia O.V., Bespalova O.N., Glotov A.S., 20252025Вашукова Е.С., Тарасенко О.А., Мальцева А.Р., Попова А.К., Пачулия О.В., Беспалова О.Н., Глотов А.С.Vashukova E.S., Tarasenko O.A., Maltseva A.R., Popova A.K., Pachuliia O.V., Bespalova O.N., Glotov A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/2287

Introduction. Currently, non-invasive prenatal testing (NIPT) is widely used to assess a risk of fetal chromosomal anomalies. NIPТ accuracy depends on the cell-free fetal DNA (cffDNA) percentage relative to total cell-free DNA in the pregnant woman's blood (cfDNA fetal fraction, FF). Despite numerous studies, no consensus regarding FF-affecting factors has been reached yet.Aim: to investigate a relationship between FF and clinical-anamnestic parameters of pregnant women, pregnancy characteristics, and outcomes using the developed NIPТ technology.Materials and Methods. A prospective observational study was performed by assessing plasma samples from 5459 women with > 9 week-long singleton pregnancies. NIPТ was performed using semiconductor sequencing followed by bioinformatics data processing, including FF determination, according to a previously developed original algorithm.Results. Median FF was 11.7 [9.5–14.0] %. It was demonstrated that FF depends on blood collection tube type (p < 0.05). FF was found to decrease with woman age and body mass index, and increase with gestational age, elevated early prenatal screening (EPS) biochemical markers – pregnancy-associated plasma protein-A (РАРР-А) and free beta-subunit of human chorionic gonadotropin (β-hCG) levels (p < 0.05). It has been shown that the FF in pregnant women with trisomy 18 is lower than normal (p < 0.05). An increase in FF was observed in pregnant women with fetal congenital anomalies according to ultrasound results (p < 0.05). No association was found between FF and the conception type, first-trimester ultrasound parameters (nuchal translucency, crown-rump length, ultrasound chromosome anomalies markers), fetal trisomy 13 and 21, fetal sex chromosome anomalies, or pregnancy complications – preeclampsia, gestational diabetes, preterm birth, and fetal growth restriction (p > 0.05).Conclusion. The identified patterns are important to take into consideration while using and interpreting NIPТ.

Введение. В настоящее время технология неинвазивного пренатального скрининга (НИПС) широко используется для определения риска хромосомных аномалий плода. Точность НИПС зависит от процента внеклеточной фетальной ДНК (вкфДНК) относительно всей внеклеточной ДНК (вкДНК) в плазме крови беременной (плодной или фетальной фракции вкДНК, ФФ). Несмотря на многочисленные исследования, до сих пор нет единого мнения о факторах, влияющих на ФФ.Цель: исследование связи ФФ с клинико-анамнестическими параметрами беременной, особенностями течения беременности и ее исходов с помощью разработанной НИПС-технологии.Материалы и методы. Выполнено проспективное наблюдательное исследование. В работе использованы образцы плазмы от 5459 женщин с одноплодной беременностью сроком более 9 недель. НИПС проводили с использованием полупроводникого секвенирования с последующей биоинформатической обработкой данных, включая определение ФФ, согласно ранее разработанному оригинальному алгоритму.Результаты. Медиана уровня вкфДНК составила 11,7 [9,47–14,01] %. Показано, что ФФ зависит от типа пробирки для сбора крови (p < 0,05). Установлено, что ФФ снижается с увеличением возраста и индекса массы тела беременной и увеличивается с увеличением срока беременности и биохимических показателей раннего пренатального скрининга (РПС) – ассоциированного с беременностью протеина-А плазмы (англ. pregnancy-associated plasma protein-A, РАРР-А) и свободной бета-субъединицы хорионического гонадотропина человека (β-ХГЧ) (p < 0,05). Показано, что ФФ у беременных с трисомией 18 ниже, чем в норме (p < 0,05). Выявлено повышение ФФ у беременных с врожденными пороками развития у плода по данным ультразвукового исследования (p < 0,05). Не обнаружено связи ФФ со способом наступления беременности, ультразвуковыми показателями РПС (толщиной воротникового пространства, копчико-теменным размером, ультразвуковыми маркерами хромосомных аномалий), нарушениями по половым хромосомам, трисомиями по хромосомам 13 и 21 у плода, а также с осложнениями беременности – преэклампсией, гестационным сахарным диабетом, преждевременными родами и задержкой развития плода (p > 0,05).Заключение. Выявленные закономерности важно учитывать при назначении НИПС и интерпретации его результатов.

неинвазивный пренатальный скринингНИПСвнеклеточная фетальная ДНКвкфДНКфетальная фракцияФФбеременностьnon-invasive prenatal testingNIPТcell-free fetal DNAcfDNAfetal fractionFFpregnancyВыражаем признательность и благодарность сотрудникам ООО «НИПТ» (Санкт-Петербург) Козюлиной П.Ю. и Моршневой А.В. за помощь в анализе данных высокопроизводительного секвенирования. Статья подготовлена к публикации в рамках выполнения фундаментальной научной темы – государственного задания Министерства науки и высшего образования Российской Федерации №1021062512052-5-3.2.2 «Разработка диагностических критериев прогнозирования и преодоления репродуктивных потерь».We express gratitude and appreciation to the employees of NIPTS LLC (Saint Petersburg) Kozyulina P.Yu. and Morshneva A.V. for assistance in analyzing high-throughput sequencing data. 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The authors declare that there are no conflicts of interest present.