Subchromosomal anomalies in small for gestational-age fetuses and newborns

Purpose To analyze copy number variants (CNVs) in subjects with small for gestational age (SGA) in China. Methods A total of 85 cases with estimated fetal weight (EFW) or birth weight below the 10th percentile for gestational age were recruited, including SGA associated with structural anomalies (Group A, n = 20) and isolated SGA (Group B, n = 65). In all cases, cytogenetic karyotyping and infection screening were normal. We examined DNA from fetuses (amniocentesis or cordocentesis) and newborns (cord blood) to detect CNVs using a single nucleotide polymorphism (SNP, n = 75) array or low-pass whole-genome sequencing (WGS, n = 10). Results Of 85 total cases, 3 (4%) carried pathogenic chromosomal abnormalities, including 2 cases with pathological CNVs and 1 case with upd(22)pat. In Group A, the mean gestational age at the time of diagnosis was 26.8 (SD 4.1) weeks and mean EFW/birth weight was 907.2 (SD 567.8) g. In Group B, the mean gestational age at the time of diagnosis was 34.1 (SD 5.8) weeks. Mean EFW/birth weight was 1879.2 (SD 714.5) g. The pathologic detection rate was 10% (2/20) in Group A and 2% (1/65) in Group B. It was inclined that the lower the EFW percentile, the more frequent the occurrence of CNVs. Conclusions Pathological subchromosomal anomalies were detected by CMA or low-pass WGS in 10% and 2% of SGA subjects with and without malformation, respectively. SGA fetuses with structural anomalies presented with higher pathological subchromosomal anomalies. The molecular genetic analysis is not recommended for isolated SGA pregnancies without other abnormal findings.