Chromosomal anomalies in fetuses with structural malformation detected by ultrasonography at 11-13+6 gestational weeks

Objective To investigate the clinical performance of ultrasound screening for fetal structural anomalies at 11-13+6 weeks of gestation and to evaluate the relation of structural anomalies with karyotypes and copy number variations. Methods A retrospective analysis was conducted on fetuses with structural anomalies detected by ultrasound examination at 11-13+6 gestational weeks in First Affiliated Hospital of Sun Yat-Sen University from January 2013 to December 2017. Karyotype and chromosomal microarray analysis(CMA) were offered to these fetuses and ultrasound scans were repeated at 16-18 gestational weeks. All fetuses were followed up to termination or birth. Fisher's exact test was used for statistical analysis. Results A total of 362 fetuses with structural anomalies were studied including 101 (27.9%) fatal malformations, 253 (69.9%) major malformations and eight (0.2%) minor malformations. Cardiac malformation (32.6%, 118/362), central nervous system anomalies (24.9%, 90/362) and anterior abdominal wall defects (20.9%, 76/362) were the three most common abnormalities. Invasive prenatal test was performed in 107 cases including 25 fatal, 79 major and three minor malformations. Thirty (28%) out of the 107 cases had abnormal karyotypes, which were chromosomal aneuploidies (n=28) and chromosomal fragment abnormalities (n=2). Among the 99 cases received CMA, 25 had abnormal karyotypes, and copy number variations were identified in eight [three (4.05%) were pathogenic variations] out of the rest 74 with normal karyotypes. The incidence of chromosomal abnormalities in fetuses with major malformations was higher than that of fetuses with fatal malformation [32.9% (26/79) vs 12.0% (3/25), P=0.045]. Altogether, 117 cases repeated second-trimester ultrasound among which 16 (13.7%) were normal; 19 (16.2%) had cardiac defect which was discordant with the first-trimester evaluation and five (4.2%) were found to have additional malformations. Diagnosis of the other 77 cases were consistent with the first-trimester ultrasound findings. After the second-trimester ultrasound scanning, 49 pregnancies were terminated; 39 twin pregnancies and four triplet pregnancies underwent selective fetal reduction; 25 continued to delivery with good neonatal outcomes. Out of the 23 699 cases without abnormal ultrasound findings at 11-13+6 gestational weeks, 20 182 (85.2%) were successfully followed up, among which structural abnormalities were found in 178 during the second trimester and in 31 after birth. Conclusions A detailed ultrasound examination at 11-13+6 weeks of gestation is important to identify fetal structural defects. However, it could not replace the second-trimester ultrasound. There is a high risk of chromosomal abnormalities in fetuses with early-detected structural defects. CMA is able to identify pathogenic copy number variations with a relatively low detection rate. Key words: Congenital abnormalities; Chromosome aberrations; DNA copy number variations; Microarray analysis