Maternal carrier screening for spinal muscular atrophy (SMA), cystic fibrosis, and hemoglobinopathies with reflex single-gene noninvasive prenatal screening (sgNIPS) delivered a personalized fetal risk estimate more accurately and timely, without the need for a paternal sample, as compared with traditional carrier screening, a study found.

Traditional carrier screening workflow results in inadequate end-to-end sensitivity for identifying high-risk pregnancies, the authors noted. Using the next-generation sequencing (NGS) of genomic DNA extracted from the buffy coat of a maternal peripheral blood sample, the sgNIPS screen first evaluates the maternal carrier status for genes linked with the most common single-gene recessive disorders, including cystic fibrosis, sickle cell disease, beta-thalassemia, alpha-thalassemia, and SMA, they added.

The study was published in the journal Genetics in Medicine.

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The sample is reflexed to sgNIPS if the pregnant individual is detected as heterozygous for a pathogenic variant in 1 or more of these genes. To determine the fetal risk, NGS is performed on the cell-free DNA extracted from the original blood sample.

In this cohort-based study, the research team assessed the clinical performance of carrier screening with reflex sgNIPS in 9151 pregnant individuals from 31 states and more than 240 providers. The analysis was done to identify the fetuses at risk for cystic fibrosis, alpha hemoglobinopathies, beta hemoglobinopathies, and SMA by comparing the sgNIPS results with those of prenatal diagnostic testing.  

Results of the study suggested that positive maternal carrier screens increased the a priori risk of having an affected fetus in both the traditional carrier screening and carrier screening with reflex sgNIPS. Moreover, the reflex sgNIPS produced an average positive predictive value of 48.3% without the need for paternal carrier screening, compared to 25% for traditional carrier screening. Furthermore, the sgNIPS sensitivity was 93.3% 

The estimated end-to-end sensitivity (including the carrier screening) was 90%, much greater than the estimated real-world end-to-end sensitivity (35%) of traditional carrier screening accomplished during pregnancy. The team noted that carrier screening with sgNIPS is a powerful and effective alternative compared to the traditional carrier screening for most individuals who have carrier screening after conception. 

In summary, the research team added that compared with traditional carrier screening, carrier screening with reflex sgNIPS might improve the prenatal identification of the affected pregnancies, the authors noted.

“It provides an sgNIPS fetal risk tailored to the pregnancy, facilitating appropriate counseling for diagnostic testing and follow-up,” the authors concluded.


Hoskovec J, Hardisty EE, Talati AN, et al. Maternal carrier screening with single-gene NIPS provides accurate fetal risk assessments for recessive conditions. Genet Med. Published online December 1, 2022. doi:10.1016/j.gim.2022.10.014