[Detection of fetal cardiac dysgenesis by SNP array technology and the variation hotspots of the local population]

Objective: To investigate the application of single nucleotide polymorphism array (SNP array) in the detection of fetal cardiac dysplasia and to explore the characteristics of chromosomal variants associated with fetal cardiac dysplasia in the local population. Methods: A total of 556 pregnant women who underwent SNP array examination in Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University from January 2021 to December 2024 because of abnormal soft index or structural malformations of fetal heart development by ultrasound examination were collected. According to the results of fetal ultrasound examination, they were divided into single abnormal soft markers group (237 cases), multiple abnormal soft index group (232 cases), soft index combined with cardiac structural abnormalities group (24 cases), isolated cardiac structural abnormalities group (47 cases), and cardiac structural abnormalities combined with other systemic abnormalities group (16 cases). According to the age of pregnant women, they were divided into ≤25 years old group (20 cases), 26-29 years old group (155 cases), 30-34 years old group (190 cases), 35-39 years old group (149 cases) and ≥40 years old group (42 cases). The differences in the detection of chromosomal abnormalities in pregnant women with different echocardiographic results and different ages were compared. Results: (1) Among the 556 pregnant women who underwent SNP array for fetal cardiac anomalies, 110 cases of fetal chromosomal variations were detected, with a detection rate of 19.8% (110/556), including 72 cases of pathogenic variations (12.9%, 72/556) and 38 cases of variants of uncertain significance (VUS; 6.8%, 38/556). Pathogenic copy number variations (CNV) involved 9 chromosomes, with 3q29, 16p13.11, 17p13.3p13.2 and 22q11.21 being the most common. (2) Among the pregnant women with different ultrasound results, the highest detection rate of fetal chromosomal variation was in the group with cardiac structural abnormalities combined with other systemic abnormalities, with a detection rate of 10/16. The detection rates of single abnormal soft index group, multiple abnormal soft index group, soft index combined with cardiac structural abnormalities group and isolated cardiac structural abnormalities group were 17.3% (41/237), 18.1% (42/232), 41.7% (10/24) and 14.9% (7/47), respectively, and the differences were statistically significant (χ²=27.680, P<0.001). (3) In different age groups, the detection rate of chromosome aneuploidy increased with age, and the detection rate of ≥40 years old group (16.7%, 7/42) was the highest. There was no significant difference in the detection rate of pathogenic CNV, VUS and chromosomal abnormalities among different age groups (all P>0.05). Conclusions: SNP array technology has important application value in prenatal diagnosis of fetal cardiac anomalies. The study on the characteristics of chromosomal variants associated with fetal cardiac abnormalities in the local population is conducive to the precise treatment of congenital heart disease.