HQ Team
December 5, 2024: Abnormal prenatal blood results are indicative of hidden cancers in pregnant women, researchers at the US nation’s medical research agency, the National Institutes of Health, found.
About half of the 107 women study participants screened using the prenatal cell-free DNA (cfDNA) testing for chromosomal disorders in the fetus were diagnosed with cancer, according to researchers at the NIH’s National Human Genome Research Institute (NHGRI), National Cancer Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Cancers included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma (bile duct cancer) and renal carcinoma.
Prenatal blood tests, known as non-invasive prenatal testing, were initiated by the child health clinic in 2011, giving parents the option to screen for the presence of extra chromosomes, such as trisomy 21 (Down syndrome), in the fetus in early pregnancy.
These tests detect freely floating DNA in the bloodstream, consisting of the pregnant person’s DNA along with placental DNA, which is genetically similar to fetal DNA.
Red blood stem cells
In addition to fetal DNA, cfDNA testing detects DNA released from the mother’s red blood stem cells and, occasionally, abnormal DNA that may result from an undetected cancer in the asymptomatic pregnant person.
“Since the tests are highly accurate and only involve a blood draw, they have quickly become routine in pregnancy screening,” according to an NIH statement. “Standard diagnostic techniques, such as taking a medical history, assessing symptoms, and physical examination, were of limited use in identifying a participant’s cancer or its location.”
During the recent analysis of the ongoing study, which began in 2019, researchers performed cancer screening of 107 participants using whole-body magnetic resonance imaging (MRI), standard medical diagnostic tests, and cfDNA sequencing.
“A total of 52 participants were diagnosed with cancer. For this group, the authors found that whole-body MRI was the most effective method for detecting cancer,” according to the statement.
“Other abnormal cfDNA results were attributed to fibroids (benign uterine tumours), placental chromosomes that differed from fetal chromosomes, and clonal hematopoiesis in the mother — a precancerous state that can lead to blood cancers.”
‘Unexpected results’
Each year, around two million pregnant people in the US undergo non-invasive prenatal testing, according to Diana Bianchi, MD, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
A few years into the use of these tests, clinicians started to see unexpected results, she said.
The blood test might indicate extra chromosomes in the fetus, but more invasive diagnostic follow-up tests — such as those that sample fluids surrounding the fetus or placental cells — might indicate a typical set of chromosomes in the fetus.
In some of these cases, the atypical results could be explained by benign tumours, autoimmune diseases, or blood abnormalities in the pregnant person. In rare cases, the pregnant person has cancer.
When a person has cancer, the tumour grows and sheds DNA into the bloodstream, which is then detected by prenatal testing methods. While there are guidelines for clinicians to order additional follow-up tests to evaluate the fetus, there aren’t any evidence-based guidelines to evaluate the pregnant person.
‘Gap in clinical practice’
“We knew that there was an association between these abnormal test results and cancer, but there is a big gap in clinical practice about what to do when a test result comes back as ‘non-reportable,’ or inconclusive,” said Dr Bianchi.
“We wanted to understand the best approach to decide which pregnant people receiving these results need further testing for cancer. Our goal is to save lives.”
The researchers also found that a specific pattern of multiple extra and missing chromosomes or parts of chromosomes was highly suggestive of the presence of cancer in the pregnant person.
They found that whole-body MRI could detect these silent cancers 98% of the time and is an effective and safe diagnostic tool for pregnant people who receive prenatal screening results suggesting malignancy.
Other lab tests that clinicians typically use to scan for cancer, such as physical examination, blood tests and faecal tests, did not seem to help diagnose cancer in these patients.
‘Fishing expedition’
When the study was initiated in 2019, “people thought we were on a fishing expedition,” said Amy Turriff, ScM, a genetic counsellor at NHGRI and first author of the paper. “Many people thought it would be unlikely to find cancer in young and healthy pregnant people, but our study challenged everyone’s expectation.”
The researchers hope to find more genetic biomarkers, or measurable substances, in the blood that may be indicative of cancer, which can help with diagnoses.
Biomarkers that are easy to test are important for people living in rural areas who may not have access to medical facilities with MRI machines.
