Blood test in pregnancy accurately diagnoses CF: Study
Unity screen could help babies get early CF treatment
The Unity Fetal Risk Screen, a test that uses a pregnant person’s blood to evaluate the fetus’s risk of cystic fibrosis (CF), accurately detected all cases of CF in a study involving more than 100,000 pregnant people.
The study found that most CF cases identified by the test are eligible for treatment with CFTR modulators, so this type of early diagnosis could help facilitate early treatment for babies with CF. The work was led by scientists at Billiontoone, the company that sells the Unity test, alongside several academic researchers.
“The ability to identify CF-affected pregnancies early in gestation, particularly those eligible for CFTR modulator therapy, represents a transformative advancement,” Aaron Trimble, MD, associate professor of medicine at Oregon Health and Science University and study co-author, said in a press release from Billiontoone.
The study, “Routine cell-free DNA prenatal screening identifies pregnancies at high risk for cystic fibrosis that may benefit from fetal therapy,” was published in the Journal of Cystic Fibrosis.
CF is caused by mutations in the CFTR gene, which provides instructions to make a protein that helps regulate mucus production. In CF, dysfunction of this protein leads to thick and sticky mucus that builds up in organs to drive most CF symptoms. CFTR modulators are medications that can increase the protein’s functionality in people with specific CF-causing mutations.
Test works with sample from only the pregnant parent
Everyone inherits two copies of the CFTR gene, one from each biological parent. CF develops if both copies are mutated. People with one mutated copy and one healthy copy are known as carriers because they will not develop CF but may pass the mutation to their biological children.
The Unity test isolates tiny amounts of fetal DNA taken from a pregnant person’s blood and tests it for CF-causing mutations in the CFTR gene. A notable advantage of this approach, according to the company, is that it requires samples only from the pregnant person, with no need for samples from the other biological parent. The test can also be done fairly quickly, with results typically available in less than two weeks.
The researchers used the test to screen 100,106 general-risk pregnancies, including 2,587 CF carriers. The study did not include people from high-risk couples — meaning those who were carriers of a CF-causing CFTR mutation and whose DNA analysis calculated a risk of a CF-affected pregnancy of at least a 1 in 4 chance of CF.
“These patients were unaware of their CF carrier status prior to [testing], demonstrating the power of this screening method for the general risk population,” the researchers wrote.
Forty of the pregnancies were identified as high risk. The researchers followed up with 20 of these, 13 of which were indeed diagnosed with CF. The test correctly identified all known affected fetuses as high risk, the team noted, meaning it had a sensitivity of 100%. At the same time, follow-up from hundreds of patients with low-risk results on the tests didn’t reveal any missed cases who were later diagnosed with CF.
All but one of the 13 babies diagnosed with CF carried at least one mutation responsive to CFTR modulator therapy. The researchers stressed that their study didn’t evaluate how early diagnosis affected treatment outcomes, but they said providing early diagnosis at such an early age could open new doors, including the possibility of using modulator therapy during a pregnancy to help prevent CF-related complications in the developing fetus.
“This could enable access to promising in utero treatments and fundamentally change outcomes for babies with cystic fibrosis,” Trimble said.
The study “validates our approach to comprehensive CF screening without requiring a partner sample, addressing a critical gap in traditional carrier screening where more than half of partners never complete testing when the pregnant mother is identified as a carrier,” said Haywood Brown, MD, chief medical officer, prenatal, at Billiontoone. “Most importantly, this gives families early insights they need to prepare for their child’s care and explore new therapeutic options that could significantly improve their child’s quality of life when CF is detected.”
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