FAQs – Section 1: Aneuploidy in Pregnancy

Aneuploidy is an abnormality in the number of chromosomes in a cell. Aneuploidy involving the autosomes, i.e. the numbered chromosomes, is usually associated with major developmental problems, e.g. trisomy 21 (Down syndrome) due to an additional copy of chromosome 21.

Aneuploidy can involve any of the different chromosomes in a cell. The most common clinically significant aneuploidies involve chromosomes 21, 18, 13, X and Y. Aneuploidy of other chromosomes can occur, but is usually associated with an early miscarriage.

Aneuploidy of the sex chromosomes (X and Y) is typically associated with less serious consequences. For example, Turner syndrome (having only one sex chromosome, an X) and Klinefelter syndrome (having three sex chromosomes, XXY) can be associated in some patients with impaired fertility but normal intellectual functioning. Harmony is an assessment for clinically significant aneuploidies involving the five chromosomes mentioned above; other aneuploidies are not considered further in this section.

This is a simple question, but the answer can be quite complex. There are three factors underlying the frequency of aneuploidy in pregnancy.

  • The first factor is maternal age. With increasing age, the chance of a woman’s unfertilised egg (ovum) having an abnormal number of chromosomes increases.
  • The second factor is gestational age. In the first few days of the pregnancy, there is a high chance that a new abnormality in the number of chromosomes will occur. This may involve all of the fetus and placenta, or just part of the fetus or part of the placenta.
  • The third factor is spontaneous miscarriage. The majority of fertilised eggs miscarry, and most of these miscarriages will be due to chromosome errors. Furthermore, most of these miscarriages will occur before a woman is aware that she is pregnant, and hence are not recognised. These miscarriages reduce the frequency of chromosome abnormalities by the third month of pregnancy (the time of NIPT) and by birth.

Overall (combining pregnant women of all ages), the chance of the developing embryo being aneuploid at the end of the first week of pregnancy is approximately 60%. The great majority of these aneuploid embryos will be lost by spontaneous miscarriage. At the 12th week of pregnancy, the chance of the fetus being aneuploid is 1-2%. Some of these abnormal fetuses will be lost due to further miscarriages, and the chance of a newborn baby being aneuploid is approximately 0.5%.

NIPT represents a test for relatively uncommon but significant conditions. This makes it a particularly challenging test to validate and provide, and is the reason that we place such a high priority on the quality of the test.

The risks of trisomy and Klinefelter syndrome rise markedly in women over 30–35 years of age. The probability of different chromosome disorders being present at 12 weeks’ gestation is shown in the Table below:

This Table does not include the probability of three sex chromosome abnormalities that can be identified by Harmony: XXX and XYY are not associated with a high probability of medical consequences, and XXYY is very rare.