Blood test may broaden prenatal genetic screening, researchers say

A new prenatal blood-testing approach may detect many fetal genetic variants now found mainly through invasive procedures, according to research being presented at the annual conference of the European Society of Human Genetics. The work matters because current noninvasive prenatal tests screen for a limited set of abnormalities, while broader testing often requires amniocentesis or chorionic villus sampling.

Dr. Christopher Whelan, a senior computational scientist in Dr. Michael Talkowski’s laboratory at the Broad Institute of MIT and Harvard and at Massachusetts General Hospital’s Center for Genomic Medicine, said the method is designed to provide diagnostic value closer to invasive genome sequencing without the procedure-related drawbacks.

The technique, called noninvasive fetal sequencing, or NIFS, analyzes cell-free fetal DNA found in a pregnant patient’s blood. According to the European Society of Human Genetics, it can screen nearly 23,000 genes while also covering the conditions currently assessed by standard noninvasive prenatal testing.

How the study was done

The researchers evaluated NIFS in 565 pregnancies at an average gestational age of 17 weeks, according to the society. They used deep sequencing of cell-free fetal DNA from maternal blood samples and computational tools to identify fetal genetic variants across the exome, the protein-coding portion of the genome.

The team checked the blood-test results against direct fetal sequencing results obtained after amniocentesis or chorionic villus sampling. The researchers reported that NIFS found about 95% to 99% of genetic variants detected by invasive sequencing, with performance varying by variant type and inheritance pattern.

For variants tied to clinically important conditions in the study, the test identified 97.2%, according to Whelan’s team. Whelan said the method also picked up clinically relevant findings that current noninvasive tests would miss.

The researchers also reported unexpected findings during testing, including twin pregnancies involving abnormal tissue and evidence that some mothers had received bone marrow transplants from male donors, which affected noninvasive prenatal test results. Whelan said those findings supported the method’s ability to detect complex signals in maternal blood.

Potential advantages and next steps

Current noninvasive prenatal tests are generally lower-resolution and vary across providers, according to the European Society of Human Genetics. Broader prenatal gene testing is now usually available through invasive methods, which Whelan said some pregnant patients decline because of fetal risk, stress, limited access and cost.

The society said NIFS is expected to cost less than invasive genome sequencing because it uses capabilities already available in many commercial diagnostic laboratories and does not require a medical procedure. The test uses slightly more sequencing than invasive genome sequencing, according to the researchers.

The researchers said NIFS may also be usable earlier in pregnancy than many abnormalities can be seen on imaging. They reported accuracy in samples taken as early as 10 weeks of gestation, including when the fetal fraction in maternal blood was as low as 3%.

Whelan’s group plans to improve NIFS so it can detect additional clinically relevant variants beyond those assessed by standard exome sequencing. The researchers are also expanding studies with the goal of making the approach available for screening in all pregnancies.

Professor Alexandre Reymond, chair of the conference and not involved in the research, said the ability to sequence a fetal genome without directly sampling fetal tissue could open earlier opportunities for treatment and prevention in reproductive medicine.

This story draws on original reporting from Medical Xpress.