Expanded Prenatal Genetic Screening Could Help Identify Chromosomal Abnormalities

Miscarriage and other abnormalities during pregnancy are often left unexplained, but a group of researchers now say that extending our prenatal screening efforts to include the sequences of all 24 human chromosomes could help to detect these issues. The researchers published their findings in the journal, Science Translational Medicine.

Women who opt for prenatal genetic screening are most often tested for extra copies of chromosomes 21, 18 and 13, with the former two being the most common chromosomal abnormalities. Trisomy 21 is the genetic aberration behind Down syndrome, while trisomy 18 causes Edwards syndrome, both of which are characterized by intellectual disability.

It’s rare that all of the chromosomes are evaluated. However, according to the researchers, if prenatal testing were expanded to include all chromosomes, it could help to identify other abnormalities and even reduce the risk of getting a false positive result from one of the established trisomy tests.

“Extending our analysis to all chromosomes allowed us to identify risk for serious complications and potentially reduce false-positive results for Down syndrome and other genetic conditions,” said senior study author Dr. Diana W. Bianchi, chief of the Prenatal Genomics and Therapy Section at NIH’s National Human Genome Research Institute (NHGRI).

In their study, Dr. Bianchi and her team analyzed DNA sequences generated from around 90,000 samples of maternal blood plasma. Nearly 73,000 of these samples were collected from women in the US, with the remainder being taken from those in Australia.

For each sample, the study investigators made predictions on whether it contained two normal copies of each chromosome using a measure known as the normalized chromosome denominator quality (NCDQ). If a sample’s NCDQ were calculated at, or below, 50, the sample underwent further analysis.

Less than one percent (0.45) of the US samples were found to be abnormal, compared to 0.42 percent of those from the Australian cohort. The most common trisomies found in both study cohorts were trisomies 7, 15, 16 and 22.

Of the 71 abnormal samples flagged in the Australian cohort, 60 were found to contain a rare trisomy. In particular, trisomies 15 and 22 were associated with early miscarriage before 12 weeks of pregnancy.

As prenatal screening for these chromosomal abnormalities is not regularly offered, women who carry these trisomies may be unaware they are at a higher risk of miscarriage. According to the researchers, a more complete panel of chromosomal sequencing should be offered to help provide this information to patients.

“We found that pregnancies at greatest risk of serious complications were those with very high levels of abnormal cells in the placenta,” said Dr. Mark D. Pertile, co-first author of the study and head of the division of reproductive genetics at Victorian Clinical Genetics Services, part of Murdoch Childrens Research Institute in Melbourne, Australia. “Our results suggest that patients be given the option of receiving test results from all 24 chromosomes.”

The NIH reports that the cost of genetic testing can be as high at $2000. It’s unclear how expanding chromosomal screening to include all 24 would affect the cost, and whether insurance providers would cover the expense.