Non-Invasive Prenatal Testing (NIPT), the cell-free DNA-based blood test that screens for fetal chromosomal abnormalities, is fast becoming a routine part of obstetric care.
NIPT at a glance
During pregnancy, maternal plasma contains fragments of DNA from the mother and from the placenta (fetal DNA).
The proportion of DNA fragments from particular chromosomes is usually very stable throughout pregnancy. If there is an excess of fetal fragments from one chromosome, the proportion of fragments from that chromosome will be changed.
A key reason that NIPTs should precisely measures the amount of fetal DNA in the sample – the fetal fraction – is if there is insufficient fetal DNA, the result may merely reflect the genetic status of the mother.
NIPT assays should report a result only if there is sufficient fetal DNA to be confident of accuracy.
Rarely, a test for trisomy 21,18 and 13 cannot be reported.
This occurs in 3% of women tested by Sonic Genetics and is usually because there is insufficient fetal DNA compared with maternal DNA in the mother’s plasma.
This low fetal fraction can be due to a relative excess of maternal DNA and this can vary over time. It is more common in women with increased body weight, and more likely in the presence of infection and inflammation, or after exercise.
It also occurs if the mother or fetus has some subtle benign variations in chromosome structure (copy number variants) that make estimating the proportion of fragments from a chromosome unreliable.
In some instances, the DNA in the sample has degraded during collection and shipping to the laboratory, and the quality is insufficient for a reliable result. These factors interfere with quality control of the test.
Two thirds of women will get a result on re-testing.
However, if the second test is inconclusive, it should not be repeated. This occurs in 1% of pregnant women screened.
It is also not worth using another form of non-invasive prenatal test. Other tests do not estimate the fetal fraction accurately and may provide false reassurance.
A decision about other test modalities (combined first trimester screen, second trimester serum screen, detailed ultrasonography or invasive genetic testing such as CVS/amniocentesis) should be based on assessment of all identified risk factors and may require specialist consultation.
More rarely (in 0.5 –1% of women) the test reports a result for trisomy 21, 18 and 13 but not for fetal gender and sex chromosome abnormalities. It is unlikely that a repeat test will provide a result. A decision about using fetal ultrasound or invasive genetic testing to document fetal gender should be based on assessment of need and any identified risk factors.
General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs.
The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.