A novel noninvasive prenatal diagnosis (NIPD) assay for β-thalassemia appears to be highly reliable and accurate and, with optimization, could serve as an alternative to traditional invasive prenatal diagnosis (IPD) for carriers of pathogenic HBB variants with pregnancy, according to study results published in BJOG.

Weigang Lv, MRes, of the Center for Medical Genetics, School of Life Sciences, Central South University in China, and colleagues conducted a retrospective study using archived plasma from 102 pregnant Chinese couples, in which both partners had a pathogenic HBB gene variant, to evaluate the clinical feasibility of using circulating single molecule amplification and resequencing technology (cSMART) for fetal genotyping.

Previously, IPD, via fetal cell sampling with amniocentesis, was used to manage these pregnancies, and HBB genotypes were determined using a standard polymerase chain reaction-based assay. The NIPD cSMART assay for HBB determines the fetal genotypes by measuring the allelic ratios in the maternal cell-free DNA.

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According to the IPD, there were 29 affected homozygotes or compound heterozygotes, 54 heterozygotes, and 19 nonaffected homozygotes. The results of the IPD and NIPD were concordant (99/102; 97%). Of the 5 discordant samples, 2 were false positives and 1 was a heterozygote carrier that was called as a nonaffected homozygote. For the novel assay, the sensitivity was 100% and the specificity was 97.26%.

The authors suggested that the unexplained discordant samples may be attributable to poor sample storage or handling. Other limitations of the study included the retrospective design and the limited coverage of the HBB gene by the current primer set.

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“Based on our findings, our cSMART test holds great promise and should have general appeal as a method of noninvasive testing for β-thalassemia at risk pregnancies,” wrote the authors. “However, before clinical implementation, the test will require further expansion to a more comprehensive and universal assay.”


Lv W, Linpeng S, Li Z, et al. Non‐invasive prenatal diagnosis for pregnancies at risk for β‐thalassemia: a retrospective study [published online May 4, 2020]. BJOG. doi: 10.1111/1471-0528.16295