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)

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.