Prevalence of chromosomal abnormalities in fetal heart defects, congenital diaphragmatic hernia and non-immune hydrops fetalis based on molecular karyotyping data (experience of the National Center)
Pak V.S., Lyushnina D.G., Naberezhnev Yu.I., Bokerija E.L., Zaretskaya N.V., Bolshakova A.S., Barkov I.Yu., Tetruashvili N.K., Trofimov D.Yu.
The prevalence of congenital fetal malformations is about 3–4%. According to the World Health Organization, about 240,000 children with congenital malformations die each year before 28 days of life, and 170,000 die before the age of 5 years. The management of patients with malformations represents a financial and human resource challenge to the healthcare system, and a significant proportion of these patients require palliative care. Therefore, the search for the causes of congenital malformations at the antenatal stage has been a priority.
Objective: To evaluate the role of chromosomal abnormalities in the development of fetal heart defects, congenital diaphragmatic hernia, and non-immune fetal hydrops.
Materials and methods: The prospective study was conducted between 2018 and 2024 and included 155 pregnant women: 61 with fetal cardiac malformation, 57 with fetal congenital diaphragmatic hernia, and 37 with non-immune fetal hydrops. The study was carried out at the National Medical Research Centre for Obstetrics, Gynecology and Perinatology in Moscow. All patients underwent invasive prenatal diagnostic procedures at different gestational ages. Fetal DNA was examined using SNP oligonucleotide chromosome microarray analysis on CytoScan Optima microarrays (Thermo Fisher Scientific, USA).
Results: The analysis of clinical and anamnestic data of the patients from the three groups did not reveal any statistically significant differences. The analysis of pregnancy complications and outcomes showed that pregnancy in the group of patients with fetal congenital diaphragmatic hernia was more often complicated by threatened preterm labor and anemia, p<0.001 and p=0.002, respectively, while patients with non-immune fetal hydrops were significantly more likely to experience antenatal fetal death, p<0.001. The study revealed that the prevalence of chromosomal abnormalities in fetuses of pregnant women of the study groups was 19.4% (30/155), including 11.6% (18/155) of cases with pathogenic copy number variations.
Conclusion: Conventional karyotyping would classify these patients as fetuses without chromosomal abnormalities. Given these findings, chromosomal microarray analysis is recommended as a first-line test in the genetic study of fetuses with congenital malformations and non-immune fetal hydrops. Since a number of fetal malformations tend to be detected late, it is recommended to perform invasive prenatal diagnostic procedures at more than 22 weeks gestation in order to provide complete perinatal counseling to the couple and to enable the family to make a reproductive choice.
Authors’ contributions: Tetruashvili N.K., Bokerija E.L., Trofimov D.Yu. – developing the concept and design of the study;
Pak V.S., Lyushnina D.G., Naberezhnev Yu.I., Zaretskaya N.V., Bolshakova A.S., Barkov I.Yu. – collecting and processing
of the material; Pak V.S., Lyushnina D.G., Naberezhnev Yu.I., Tetruashvili N.K. – writing the text; Pak V.S., Lyushnina D.G. – statistical processing of the data; Tetruashvili N.K., Bokerija E.L., Bolshakova A.S., Barkov I.Yu., Trofimov D.Yu. – editing the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The study was carried out without sponsorship.
Ethical Approval: The study was approved by the Ethical Review Board of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
Patient Consent for Publication: The patients signed informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Pak V.S., Lyushnina D.G., Naberezhnev Yu.I., Bokerija E.L., Zaretskaya N.V., Bolshakova A.S., Barkov I.Yu.,
Tetruashvili N.K., Trofimov D.Yu. Prevalence of chromosomal abnormalities in fetal heart defects, congenital diaphragmatic hernia and non-immune hydrops fetalis based on molecular karyotyping data
(experience of the National Center).
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (12): 33-41 (in Russian)
https://dx.doi.org/10.18565/aig.2024.281
Keywords
fetal heart defect
congenital diaphragmatic hernia
non-immune fetal hydrops
chromosomal microarray analysis
molecular karyotyping
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Received 07.11.2024
Accepted 05.12.2024
About the Authors
Viktoriia S. Pak, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(913)897-28-49, v_pak@oparina4.ru, https://orcid.org/0009-0002-1444-9071Daria G. Lyushnina, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,
4 Acad. Oparin str., Moscow, Russia, 117997, +7(906)308-60-78, d_lyushnina@oparina4.ru, https://orcid.org/0009-0004-3160-8737
Yu. I. Naberezhnev, PhD, Head of the Department of Perinatal Care, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(910)323-12-47, rubick@yandex.ru, https://orcid.org/0000-0003-2547-9735
Ekaterina L. Bokerija, PhD, Researcher at the Department of Patology for Newdorn and Prematurely-Born Children No. 2, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-27-05,
e_bokeriya@oparina4.ru, https://orcid.org/0000-0002-8898-9612
Nadezhda V. Zaretskaya, PhD, Head of the Laboratory of Clinical Genetics of the Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-24-11,
n_zaretskaya@oparina4.ru, https://orcid.org/0000-0001-6754-3833
Anna S. Bolshakova, MD, Geneticist, Department of Clinical Genetics of the Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-24-11, a_bolshakova@oparina4.ru, https://orcid.org/0000-0002-7508-0899
Ilya Yu. Barkov, PhD, Head of the Laboratory of Prenatal DNA Screening of the Institute of Reproductive Genetics Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-24-10, i_barkov@oparina4.ru, https://orcid.org/0000-0001-6297-2073
Nana K. Tetruashvili, PhD, Head of the Obstetric Department of Pregnancy Pathology No. 2, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, +7(495)438-14-77, n_tetruashvili@oparina4.ru,
https://orcid.org/0000-0002-9201-2281
Dmitry Yu. Trofimov, PhD, Professor of the RAS, Corresponding Member of the RAS, Director of the Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-49-51,
d_trofimov @oparina4.ru, https://orcid.org/0000-0002-1569-8486
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