Foetal testing in the future

Imagine a world where chromosomal abnormalities could be detected – and fixed – while a foetus is still in the womb.

Within the next 10 years, in-utero surgery will provide parents with the option of having a chromosomal repair performed before a baby is born, says Professor Ermos Nicolaou, specialist obstetrician and gynaecologist, and specialist in maternal and foetal medicine at Mediclinic Morningside. Together with an international team, Professor Nicolaou has already performed successful spinal surgery on a foetus with spina bifida.

“We aren’t there yet, but if we continue with the development and research that’s happened over the past decade, I believe there’ll be a lot more we’ll be able to discover and determine about the foetus through non-invasive prenatal testing (NIPT),” he says.

“For instance, a balanced translocation is when a parent usually has all the genetic material necessary for normal growth—a piece of a chromosome is merely broken off and attached to another one. However, when that person’s cells divide to create an egg or sperm cells for reproduction, the egg or sperm cells can end up with extra genetic material or missing genetic material.” Professor Nicolaou says it’s just a question of time before NIPT will allow medical professionals to detect this scenario and to fix it before the baby is born.

To determine a baby’s risk of particular chromosomal abnormalities, such as Down syndrome, Edwards syndrome and Patau’s syndrome, these are the current options:

1. Ultrasound, plus careful observation and assessment. Foetal measurements are entered into a database in order to calculate the risk of abnormalities.
2. Chorionic villus sampling (CVS). This test, which involves a sampling of the placental tissue (chorionic villi), is offered between 11 and 14 weeks of pregnancy. “When the mother is under local anaesthetic, we pass a very fine needle through her abdomen, directly into the placenta, where a sample of chorionic villi is taken,” Professor Nicolaou explains. “The needle is then removed. The entire procedure, which takes about one minute, is performed under careful ultrasound scan observation. The tissue sample is then analysed in a laboratory and an ultrasound scan is done to assess the foetal heart rate and confirm foetal wellbeing. The risk of miscarriage with this procedure is 1%.”
3. Amniocentesis, which entails the aspiration of amniotic fluid, is offered after 16 weeks’ gestation. Professor Nicolaou says the results are available within three working days for Trisomies 21, 18 and 13 (Down, Edwards and Patau’s syndromes), and up to two weeks for a full chromosomal analysis (karyotype). The risk of miscarriage with this procedure is also 1%.

Professor Nicolaou adds that non-invasive prenatal tests, which were introduced around 2016, are becoming a lot more popular. This is because they pose no risk of miscarriage and give very accurate results with a negative predictive value. “In other words, when the test says the baby doesn’t have Down syndrome, it’s 100% accurate. However, NIPTs have a 97-99% positive predictive value, meaning we’d then need to do a more invasive procedure – such as CVS or an amniocentesis – to confirm or exclude whether the baby has Down syndrome.”

NIPTs require a blood sample from the mother, from which foetal DNA is extracted. The accuracy of detection for Down syndrome (21 chromosomes), Edwards syndrome (18 chromosomes) and Patau’s syndrome (13 chromosomes) are 99%, 97%, and 92%, respectively. The blood has to be couriered to a laboratory in the United States and results can take up to two weeks.

“We’ve always suspected that there are foetal cells in the maternal blood,” Professor Nicolaou explains. “Cells from the baby’s skin and the placenta feed into the maternal circulation [mother’s blood] and this is called cell-free DNA. For years it was an almost impossible task to harvest and test foetal DNA successfully, but now we have the appropriate technology to identify foetal DNA, harvest it and amplify it. With time, experience and numbers, the accuracy rates of NIPTs will improve.”