Non-immune hydrops fetalis: improved diagnosis

The incidence of this pathology ranges from 1:1700 to 1:3000 cases. NIHF is a rare condition that occurs during pregnancy and is characterized by excessive fluid accumulation in two or more fetal body cavities and tissues (ascites, pleural effusion, hydropericardium, and generalized skin edema) in the absence of alloimmunization. Both the clinical picture and prognosis of the fetus depend on the timing of the disease manifestation, amount of fluid, and volume of the lesion.

Researchers worldwide are investigating the causes of this pathology. According to the literature, chromosomal aneuploidies are more common in the early stages of pregnancy (first trimester) and manifest on ultrasound with an increase in the thickness of the nuchal translucency, generalized fetal edema, and gross malformations.

The primary causes of NIHF in later stages of pregnancy include cardiovascular abnormalities, infections, gastrointestinal and respiratory pathologies, hematological disorders, severe fetal anemia, lymphatic dysplasia, and monogenic diseases.

The range of causes of NIHF is expanding due to improvements in diagnosis. However, in most cases, the etiology of NIHF is still unknown, which is attracting the attention of many researchers. According to specialists from the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, determining the etiology of NIHF helps to optimize prenatal care and in some cases save the life of the child. In addition, identification of the genetic causes of the disease allows parents to be informed about the prognosis and risk of having a child with NIHF in subsequent pregnancies.

In their article, the authors described two clinical cases illustrating the antenatal diagnosis of rare lysosomal storage diseases (LSDs) that may be the cause of non-immune hydrops. These are Sly syndrome, identified in a fetus with NIHF at 21-22 weeks of gestation, and galactosialidosis, diagnosed at delivery.

The examination of pregnant women with NIHF was carried out according to the algorithm developed at the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. DNA samples from the fetus and parents were studied using chromosomal microarray analysis and special examination methods, including whole exome sequencing and Sanger sequencing. To analyze pathogenicity, a joint analysis of data from whole exome sequencing of the fetus and parents (trio-whole exome sequencing) was also performed.

After receiving data from genetic testing of the parents, geneticists determined the type of inheritance of these diseases. Both parents in each observation were carriers of probable pathogenic variants in the GUSB and CTSA genes associated with autosomal recessive diseases.

Genetic counseling was provided to the parents to inform them about the high risk of recurrence of this pathology in subsequent pregnancies (25% of adverse outcomes) and the possibility of preimplantation or prenatal diagnosis.

Thus, the proposed examination makes it possible to optimize pregnancy management tactics, predict the risk of identified pathology in subsequent pregnancies, and expand the possibilities for genetic counseling.

The authors conclude that the proposed examination enables the optimization of pregnancy management strategies, prediction of the risk of identified pathology in subsequent pregnancies, and expands the possibilities of genetic counseling.