NUS researchers at the Department of Obstetrics and Gynaecology led by Assistant Professor Mahesh Choolani have been trying to develop a new way of prenatal diagnosis which is non-invasive.
With couples having babies at a later age, this research is especially pertinent. In Singapore, one in five pregnancies occurs in mothers above 35. As later pregnancies carry with them higher risks of chromosomal abnormality, it is advisable that mothers in this age-group go for prenatal screening.
Without prenatal diagnosis, one in 50 babies is born with serious physical or mental handicap. And as many as one in 30 will have some form of congenital malformation. However, current methods require invasive testing and carry a 1 per cent risk in miscarriage. These methods are amniocentesis, chorion villus biopsy and foetal blood sampling.
Amniocentesis is a diagnostic procedure in which a small amount of amniotic fluid is withdrawn through a needle inserted through the mother's abdominal wall into the uterus. It is then examined in a laboratory to detect genetic abnormalities in a foetus.
Chorion villus biopsy (CVB) involves extracting a sample of the developing placenta from the uterus using a fine needle inserted through the abdomen. Chrionic villi are fingerlike projections of a membrane that surrounds the fetus. As the villi develop from the fertilised egg, they would have a genetic composition similar to that of the foetus.
The third method of testing, foetal blood sampling, involves taking a blood sample from the baby while it is still in the womb.
Non-invasive prenatal diagnosis
Since foetal cells can enter and circulate within the mother's blood, analysis of these cells would thus allow early detection of abnormalities.
The team has identified foetal nucleated "erythrocytes" (bone marrow cells which later become red blood cells) as ideal for non-invasive prenatal diagnosis. These cells have to be extracted from the maternal blood. They then have to be identified as foetal -- this is more or less a "distilling" process - necessary because only "pure" foetal cells can yield an accurate diagnosis.
The identification and diagnosis procedures used to be time-consuming and painstaking - with a cell loss of as high as 18 per cent. However, since embarking on this research in 1999, Dr Mahesh and team have managed to combine the two procedures- identification and diagnosis of the cells -- into a single simultaneous technique using FISH (Fluorescence in situ hybridisation). FISH is a process which marks chromosomes with fluorescent molecules. Their findings were published BLOOD in 2001 and their diagnosis method was patented in UK.
The first phase - that of extracting target cells from the mother's blood is now the last hurdle. "Finding a foetal cell is like finding a needle in a haystack. There is only one foetal cell to every millilitre of maternal blood. This translates to one foetal cell per 10 million maternal nucleated cells," said Dr Mahesh.
This work is part of the Foetal Genetics Biomarker Discovery Programme being carried out at the Diagnostic Biomarker Discovery Laboratory at NUS Clinical Research Centre. The team, working with the Institute of Bioengineering and Nanotechnology under a Biomedical Research Council Grant of $500,000 is now exploring the use of nanotechnology to help them overcome this problem.
"The cell is too small and there are too few to work with. So we need nanoscience to separate these little cells and to get them out from the blood," explained Dr Mahesh who is also Director, Postgraduate Education, O & G Department.
Through nanotechnology, they are developing a filter which would stream the target cells to a fixed destination where the diagnosis test can be conducted. They expect to produce results within five years for clinical trials to take place.
If all goes well, the "Holy Grail of prenatal diagnosis" would be available within 10 years, said Dr Mahesh.