Correlation between types of Ventricular Septal Defect and chromosomal abnormalities in Low-Risk Non-Invasive Prenatal Testing

1 Clinical dataThis retrospective cohort study was conducted at Tianjin Central Hospital of Obstetrics and Gynecology and included pregnant women who underwent amniocentesis due to fetal VSD between May 2017 and May 2022. Those who were diagnosed with either isolated VSDs or non-isolated VSDs through echocardiography were included in the study, while pregnant women without Non-Invasive Prenatal Testing (NIPT), those at high risk of NIPT, and those with genetic disorders were excluded. The focus of the analysis was on the population undergoing amniocentesis due to fetal VSD under the condition of low-risk NIPT. High-risk NIPT cases, which included chromosomal number abnormalities, segment deletions or duplications, and polymorphisms, were also taken into consideration. To monitor the pregnancy outcomes, phone calls were made and newborns were followed up for at least six months after delivery. Postpartum diagnoses and prognoses were documented, including those that required surgical intervention and those that healed naturally without surgery, either inside or outside the uterus. 2 The ultrasonic diagnosis criteria and classification of fetal VSDThe transabdominal ultrasound was conducted using the GE Volson E10 color Doppler ultrasound diagnostic instrument, accompanied by the C1-5-D probe of 3.5-5.5MHz frequency. Diagnosis of fetal VSD was determined by the presence of a continuous disruption of the ventricular septum in the parasternal four-chamber view, and enhanced echo at the septal end, which was made visible with the use of color Doppler imaging. This diagnosis was made by cardiac ultrasound experts with more than 5 years of experience in our hospital.The presence of other cardiac and extracardiac abnormalities on ultrasound examination was used to divide VSD into isolated and non-isolated types. Isolated VSD was further divided into muscle defect and non-muscle defect groups, with the latter including perimembranous and mixed-type defects. Non-isolated VSD included intracardiac and extracardiac structural abnormalities, such as atrioventricular septal defect, coarctation of the aorta, and Fallot's tetralogy. Additionally, extracardiac abnormalities could include Fetal Growth Restriction (FGR), lateral ventricles expansion, double renal pelvis expansion, digestive tract obstruction, hypospadias, and short long bones. 3 Chromosomal examinationChromosome G banding karyotype analysis and CNV seq based on high-throughput sequencing were conducted at 18-24 weeks of gestation, with Fluorescence in situ hybridization (FISH) and CNV-seq also performed at more than 24 weeks. The results of CNV-seq were classified according to the ACMG2019 guidelines, which included Pathogenic (P), Likely Pathogenic (LP), Uncertain Significance (VUS), Likely Benign (LB), and Benign (B). After a comprehensive analysis of CNV seq and G banding karyotype analysis/FISH, the cases in this study were categorized as non-probable pathogenic (LP) CNV patients, which were divided into pathogenic CNV (P) and nonpathogenic CNV. The latter included CNV of unknown clinical significance and benign CNV. Women and their families could then decide to continue or terminate the pregnancy based on the presence of pathogenic CNV, gestational age, and the severity of fetal structural abnormalities.4 Statistical analysisSPSS 24.0 was utilized in data processing. To compare the incidence of pathogenic CNV in various kinds of VSD and the rate of surgical intervention between the groups, χ2 test (with continuous correction or Fisher's test) was employed. A P-value of less than 0.05 showed that the difference was statistically significant.Table 1 Incidence of pathogenic CNV of different types of VSDTable 2 Comparison of the incidence of pathogenic CNV in different groupsTable 3 Clinical data and pregnancy outcome of 7 fetuses with pathogenic CNVTable 4 Clinical data and pregnancy outcome of 7 fetuses with CNV of unknown clinical significanceTable 5 Surgical interventions in 59 neonates with normal and surviving CNVs