Prenatal genome sequencing
Photo source: NHGRI, Ernesto del Aguila III
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This article waslast modified on November 6, 2017.

A recent study in Science Translational Medicine found that examining all 24 chromosomes (22 pairs of autosomes plus the X and the Y sex chromosomes) during prenatal screening can be used to identify additional disorders not currently detected by traditional non-invasive prenatal screening (NIPS). This may help improve the scope of disorders detected by prenatal genetic screening.

Non-invasive prenatal screening (NIPS) is typically performed around the 10th week of pregnancy and involves drawing a sample of the mother's blood, which contains genetic material released by the placenta. This circulating cell-free DNA (cfDNA) generally reflects the genetic makeup of the developing baby (fetus). NIPS analyzes cfDNA to identify chromosome abnormalities and imbalances, typically focusing on determining whether chromosomes 21, 18, and 13 are present in three copies instead of two. These trisomies are associated with Down syndrome, Edwards syndrome, and Patau syndrome, respectively.

Though the American College of Medical Genetics and Genomics (ACMG) recommends NIPS as the most sensitive method for prenatal Down syndrome screening, NIPS typically focuses solely on 13, 18, 21, X and Y and does not evaluate any of the other chromosomes. According to the new study, using a blood sample from the mother, the placental cfDNA can be evaluated to look at all chromosomes, not just the five that are currently evaluated. This method allows for the identification of trisomies and chromosome imbalances for all the chromosomes.

For the new study, researchers reviewed the data from whole genome sequencing of almost 90,000 blood samples obtained during or after the 10th week of pregnancy from women in two groups: one in Australia and one in the U.S. They found that 71 samples (0.42%) from the Australian group and 328 samples (0.45%) from the U.S. group had abnormalities of chromosomes other than 13, 18, 21, X or Y.

Trisomy 7 (an extra chromosome 7) was the most commonly identified additional trisomy in both study groups, followed by trisomies 15, 16, and 22. In 52 patients from the Australian group, 22 of those abnormal NIPS results were associated with miscarriages occurring before 11 or 12 weeks of pregnancy, and three were associated with fetal death in the second or third trimester.

The researchers suggest that in the future, pregnant women should be given the option of NIPS for all chromosomes, rather than a select few. Additional study is needed before this screening could be used in clinical care. For example, fourteen samples were flagged as showing a chromosomal abnormality by NIPS but resulted in healthy pregnancies, indicating that false-positive results remain an issue for NIPS. The number of pregnancies for which follow-up was available was low compared to the number of pregnancies included in the study. In addition, validation of the analysis of all chromosomes will need to take place in the clinical lab setting prior to offering the test to patients.

As is the case with current NIPS, any woman considering genetic prenatal screening should receive pre-test genetic counseling as well as post-test genetic counseling for any abnormal results, followed by confirmatory studies using a diagnostic test like chorionic villus sampling (CVS) or amniocentesis.

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Tests: Cell-free Fetal DNAAmniotic Fluid Analysis 
Conditions: Pregnancy

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(August 30, 2017) Sequencing all 24 human chromosomes uncovers rare disorders. National Institutes of Health Press Release. Available online at Accessed September 21, 2017.

Pertile M, et al. Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease. Science Translational Medicine. 30 Aug 2017: Vol. 9, Issue 405, eaan1240. Abstract available online at Accessed September 2017.

© 2017 Mayo Clinic. Prenatal cell-free DNA screening. Available online at Accessed September 2017.