Most women enjoy a healthy pregnancy. Some babies, however, are born with problems and about one-sixth of these are due to chromosome abnormalities. There are 46 chromosomes in each cell of our bodies, arranged in 23 different pairs with one pair coding for sex (XY for boys and XX for girls). The most common chromosome abnormality is Down syndrome which occurs when there is an extra copy of chromosome 21 in every cell, which is why it is also referred to as trisomy 21. Down syndrome is associated with mild to moderate intellectual disability and may also lead to digestive issues and congenital heart defects. It is estimated that Down syndrome is present in 1 out of every 800 newborn. Babies can be conceived with additional copies of chromosome 18 (Edwards syndrome) or 13 (Patau syndrome). These syndromes are associated with high rates of miscarriage or stillbirth and surviving babies have major anatomic abnormalities, intellectual handicap and a shortened lifespan. They occur in about 1 in every 5000 – 13000 live births.
Sex chromosome conditions occur when there is a missing, extra, or incomplete copy of one of the sex chromosomes which are seen in 1 out of every 1000 newborns. There is significant variability in the severity of these conditions with most individuals having mild, if any, physical or behavioural features, but they often face growth and reproductive disorders.
Current screening for chromosome abnormalities in early pregnancy
The main form of screening in Australia combines ultrasound features of the baby at 11-14 weeks (nuchal translucency measurement of a small pocket of fluid at the back of the baby’s neck] and assessment of the fetal nasal bone) with measurement of chemicals that come from the placenta into your bloodstream (free beta hCG and PAPP-A) to create an individual risk for trisomies 21, 18 and 13. It is unable to provide risk assessment for the sex chromosome abnormalities. If the risk is elevated (a figure higher than 1 in 300), then definitive chromosome testing by invasive sampling of the placenta (chorionic villus sampling [CVS] at around 12 weeks) or amniocentesis (at around 16 weeks) is discussed. These tests can identify all chromosome abnormalities (not just trisomies 21, 18 and 13) and new DNA technology can also detect a wide range of genetic abnormalities.
This form of screening is able to detect approximately 92% of the major trisomies. It is important to know that most of the women who fall into the ‘increased risk’ group have perfectly normal babies (these are called false positive screening results) and they experience considerable anxiety as well as undertaking invasive tests that have a small miscarriage risk.
Non-invasive prenatal testing (NIPT)
This test can detect a small amount of baby’s DNA in the mother’s bloodstream. Testing of this DNA can identify the vast majority of babies with trisomies 21, 18 and 13 and the major sex chromosome abnormalities.
The blood test can be performed from 10 weeks onwards. It is important to have an ultrasound scan before the blood test to confirm the baby is progressing normally. The blood test can also be performed in twin pregnancies, but not in triplets or higher order multiples. The cost of NIPT testing is approximately $445 with Sydney Ultrasound for Women.
This test is not 100% accurate and cannot look at all chromosomes and their arrangement, therefore it cannot replace CVS or amniocentesis. The result will usually take the form of a “low risk” (less than 1 in 10,000 chance of an affected baby) or “high risk” (greater than 99% chance of an affected baby). As the test can sometimes produce a false high risk result, absolute confirmation of the abnormality by CVS or amniocentesis is important before making any decisions about the pregnancy.
Another consideration is that occasionally the percentage of baby’s DNA in the blood stream is too low (< 5%) to produce an accurate result. This circumstance arises in 1 in every 50 NIPT tests and will require another blood sample to be drawn, delaying the results by a further two weeks.
There has been a lot of enthusiasm for NIPT from both doctors and consumers but finding the right place for this test in the early pregnancy screening process, taking into account the benefits and limitations of NIPT, has been a little difficult. NIPT is essentially a very accurate screening test that complements traditional first trimester ultrasound-based screening. Combining this with the 11-14 week ultrasound screening of the nuchal translucency maintains the benefits of ultrasound (detection of structural abnormalities, assessment of risk for congenital heart defects and certain genetic syndromes) and placental biochemistry (risk assessment for early severe high blood pressure in pregnancy and other adverse outcomes) whilst improving the detection rate for the common chromosome abnormalities to above 98%.
There are two current approaches to NIPT testing. The first is to do the NIPT blood test at 10 weeks and follow this with the ultrasound and placental biochemistry blood test at 12-13 weeks, getting all the results at one time. The other approach is do the traditional first trimester screening at 12 weeks to derive an individual risk for the common chromosome problems. If the risk is very high (above 1 in 50) then definitive testing by CVS would be most appropriate as the risks for other rare chromosome problems and genetic syndromes are also increased in this group of women and these are not covered by the blood test. A Down syndrome risk below 1 in 1000 may be sufficiently reassuring for you to do no further testing. About 8% of women have a risk between 1 in 50 to 1 in 1000 and they often like the reassurance provided by NIPT.
This blood test is an exciting development in prenatal screening and can significantly reduce the number of invasive diagnostic tests that are performed, but it does have some limitations and may not be for everyone. You should talk to your doctor and the prenatal screening specialist to get the most up-to-date information on this fast changing area to decide what is the best approach for you and your baby.
By Dr Andrew McLennan