Significance of Low Maternal Serum B-hCG Levels in the Assessment of the Risk of Atypical Chromosomal Abnormalities

Introduction: The introduction of prenatal cell-free DNA as a screening test has surpassed traditional combined first-trimester screening (cFTS) in the detection of common trisomies. However, its current limitation in detecting only common trisomies is affecting the diagnostic yield for other clinically significant chromosomal abnormalities. Methods: In efforts to optimize the detection of fetuses with genetic abnormalities, we have analyzed the relationship between the cFTS risk score and biomarkers with atypical chromosomal abnormalities. Furthermore, we have evaluated the impact of prenatal cell-free DNA screening on the detection of chromosomal abnormalities in our population. For these purposes, we performed a retrospective study of 877 singleton pregnancies who underwent chromosomal microarray analysis (CMA) between 2013 and 2020 and for whom cFTS data were available. Results: The results demonstrated that low levels of free beta-human chorionic gonadotropin (beta-hCG) (<= 0.37 multiples of the median) and increased fetal nuchal translucency (NT) (>= 3.5 mm) were statistically associated with the presence of atypical chromosomal abnormalities. In fact, the risk of pathogenic CMA results increased from 6 to 10% when fetal NT was increased and from 6 to 20% when a low serum beta-hCG level was detected in the high-risk cFTS group. Moreover, our results showed that altered serum levels of beta-hCG can have a substantial impact on the early detection of clinically relevant copy number variants. Discussion/Conclusion: Traditional cFTS can potentially identify a substantial proportion of atypical chromosomal aberrations, and women with increased NT or low maternal serum beta-hCG levels are at increased risk of having pathogenic CMA results. Our results may help clinicians and women decide whether invasive testing or prenatal cell-free DNA screening testing is more appropriate for each situation. (C) 2021 The Author(s).

Automated summary

The study found that low levels of free beta-hCG and increased fetal NT were statistically associated with atypical chromosomal abnormalities; additionally, altered serum levels of beta-hCG have a substantial impact on the early detection of clinically relevant copy number variants; traditional cFTS has the potential to identify a significant proportion of atypical chromosomal aberrations, with women with increased NT or low maternal serum beta-hCG levels at an increased risk of having pathogenic CMA results.