Analysis of tissue from pregnancy loss and aborted fetus with ultrasound anomaly using subtelomeric MLPA and chromosomal array analysis

Objective To evaluate the incidence and types of chromosomal abnormalities in pregnancy loss and aborted fetuses with anomaly and compare the performance of subtelomeric MLPA and chromosomal microarray analysis (CMA) in these specimens. Methods Samples were collected from spontaneous miscarriages, stillbirths and aborted fetuses with anomaly between January 2015 and April 2019. Chromosomal abnormalities were detected using subtelomeric MLPA and CMA. Results Among the 172 miscarriage samples, CMA detected pathogenic chromosomal abnormalities in 88 cases. MLPA could identified all aneuploidies and most pathogenic CNVs, missing all polyploidies; Of the 30 stillbirths, one pathogenic CNV and two VOUS were identified by CMA, all of which were missed from MLPA; Of the 135 aborted fetuses with anomaly, CMA identified pathogenic chromosomal abnormalities in 32 fetuses (23.7%); 18.95% in fetuses with isolated, and 35% in fetuses with multiple anomalies. MLPA can identify all aneuploidies but missing most pathogenic CNVs. Conclusion Our systematical comparison of subtelomeric MLPA and CMA for chromosomal analysis of tissue from pregnancy loss and aborted fetuses with anomaly is useful for assessing clinical utility of these techniques. MLPA screening, coupled with CMA analysis, is a cost-effective approach to detect chromosomal abnormalities in miscarriage and anomalous fetuses. However, MLPA might not be appropriate for chromosome analysis in stillbirth without structural anomaly; further research with more samples is needed.