Application of Copy Number Variation Detection to Fetal Diagnosis of Echogenic Intracardiac Focus During Pregnancy.

Yaxian Song,Fang Yang,Jiong Gao,Wen Liu,Jing Wang,Limin Wu,Guoping He,Hongmiao Li,Yue Hu,Jingjing Xu,Xiaohua Jiang,Yaqin Peng

doi:10.3389/fgene.2021.626044

Abstract

Echogenic intracardiac focus (EIF) is one of the most common ultrasound soft markers (USMs) in prenatal screening. However, the association of EIF with chromosomal abnormalities is still controversial. From January 2018 to April 2020, a total of 571 fetuses with USMs in our center were enrolled, among which 150 (26.27%) presented EIFs. We analyzed the karyotype anomalies and copy number variations (CNVs) in fetuses who presented EIFs by comparing their ultrasound indications, maternal ages and gestational stages. There were no statistically significant differences in the incidence of chromosomal abnormalities between fetuses with EIFs and the fetuses with USMs (4.00 vs. 7.71%, p = 0.112). Additionally, the incidence of chromosomal abnormalities was not related to maternal age (4.10% in maternal age below 35 yeas vs. 3.57% in maternal age above 35, p = 1.000). Interestingly, after 28 weeks of gestation, fetuses with EIFs showed more chromosomal abnormalities (20.00%) than that in the group before 28 weeks of gestation (2.22%, p = 0.014), and this result was attributed to the detection of pathogenic CNVs. After birth, 25 of children conducted cardiac development re-examination. Among them, 9 (36%, 9/25) were diagnosed with congenital heart disease, primarily patent foramen oval and ventricular septal defects (7/9, 77.77%). We concluded that the appearance of EIFs in early or mid-trimester would not indicate an increased risk of fetal chromosomal abnormalities. However, the persistence of EIFs in late trimester was associated with a higher risk of pathology-related CNVs and its persistent appearance may indicate heart development defects after birth. Thus, our results suggest that CNV detection has its advantages in prenatal diagnosis, especially for those with EIFs that persist in the third trimester.

Highlights

Ultrasound screening in the first and second trimesters of pregnancy is one of the most commonly performed genetic screenings
From year 2018 to 2020, among 3,377 cases of prenatal diagnosis in our center, the incidence of Echogenic intracardiac focus (EIF) identified by sonographic screening was 4.44% (150 in 3,377); and the most common cardiac lesions were in the left ventricle (75.33%), in accordance to the previous literatures (How et al, 1994; Bromley et al, 1995, 1998; Wax et al, 2000; Nyberg et al, 2001; Wang et al, 2018)
We analyzed the risk of fetal chromosomal abnormalities by both karyotyping and copy number variations (CNVs)-seq

Summary

Introduction

Ultrasound screening in the first and second trimesters of pregnancy is one of the most commonly performed genetic screenings. An increased incidence of trisomy 21 was found in fetuses who presented EIFs in high-risk pregnancies, some studies had failed to show this association (Dildy et al, 1996; Simpson et al, 1996; Achiron et al, 1997; Bromley et al, 1998; Manning et al, 1998; Winter et al, 2000). It was reported that 6.0% of fetuses presenting structural anomalies under ultrasound scanning had abnormal CNVs even karyotypes were normal (Wapner et al, 2012). The CNV character in fetuses with EIFs is still seldom revealed

Methods

Results

Conclusion