Prenatal diagnosis and pregnancy outcomes in fetuses with vertebral abnormalities

To investigate the genetic risk and pregnancy outcomes of fetuses who had the sonographic diagnosis of vertebral abnormalities (VA).

Fifty-two fetuses with sonographically detected VA (excluding neural tube defects) were included in the study. Data on prenatal ultrasound scan, prenatal genetic testing by amniocentesis, and pregnancy outcomes were collected and reviewed.

Four types of VA were identified among 52 fetuses: butterfly vertebrae (26.9%, 14/52), hemivertebrae (59.6%, 31/52), hemivertebrae combined with butterfly vertebrae (9.6%, 5/52), and block vertebrae (3.9%, 2/52). Of the 52 fetuses, 33 presented VA as the sole sonographic anomaly, while the remaining 19 had associated anomalies. The positive rate of prenatal diagnosis for fetuses with VA was 19.2% (10/52). Chromosomal analysis, including karyotyping and chromosomal microarray analysis (CMA), detected one case of mosaic trisomy 9 and six cases of (likely) pathogenic copy number variants (CNVs). Whole exome sequencing (WES) identified four likely pathogenic variants in three cases with negative CMA results, specifically c.5110-1G > A in FLNB, c.8366G > A in KMT2D, and c.1275_1283dup as well as c.870 + 2T > C in DLL3. Among the 10 cases with diagnostic genetic testing results, seven fetuses exhibited isolated VA. There was no significant difference in the diagnostic rates between the isolated VA group (21.2%, 7/33) and the non-isolated VA group (15.8%, 3/19) (odds ratio [OR] 0.696, 95% confidence interval [CI] 0.157-3.087, p = 0.910). However, the live birth rate was significantly higher in the isolated VA group (71.9%, 23/32) compared to the non-isolated VA group (38.9%, 7/18) (OR 4.016, 95% CI 1.184-13.622, p = 0.022). Among the 30 live birth cases, two underwent spinal surgery and another two were identified with additional abnormalities. Following appropriate interventions, no apparent abnormalities were observed in the growth and development of 30 live birth cases.

Invasive prenatal diagnosis is recommended for all fetuses diagnosed with VA, regardless of whether associated anomalies are present. WES can enhance the diagnostic yield for fetuses with negative CMA results. Fetuses with isolated VA can have favorable pregnancy outcomes when genetic testing results are negative. However, long-term follow-up remains necessary for the assessment of the prognosis of these fetuses.