Non-invasive prenatal testing (NIPT)

In non-invasive prenatal testing (NIPT), a maternal blood sample is used to screen for common fetal aneuploidies. Aneuploidy is the presence of an atypical number of chromosomes in a cell. The three types of aneuploidy currently screened for in pregnancy are Patau syndrome (trisomy 13), Edward syndrome (trisomy 18) and Down syndrome (trisomy 21). NIPT is also available privately, where a wider range of aneuploidies may be screened for.

NIPT is performed using a sample of maternal blood. This contains a mixture of maternal DNA and placental DNA, known as cell-free DNA (cfDNA). In most cases, the placental DNA will be representative of the fetal genome.

The cfDNA can be isolated, and it is possible to identify which chromosome each isolated fragment of DNA comes from. Techniques that can be used for this include next-generation sequencing and microarray. By looking at the proportions of fragments derived from each chromosome, it is possible to determine whether there is an excess of fragments from any particular chromosome.

Advantages

• There is no need to take a sample from inside the uterus (in contrast with invasive prenatal diagnosis using amniotic fluid or chorionic villus sampling). This removes the small chance of miscarriage associated with invasive procedures.
• It is available for twin pregnancies.

Limitations

• It is not designed to detect fetal genetic conditions other than the targeted aneuploidies (some of these, for example cystic fibrosis, may instead be tested for using non-invasive prenatal diagnosis).
• Currently, NIPT is only available on the NHS to women who have had a screening blood test result (NHS combined or quadruple test) that suggests there is a high chance of fetal trisomy.
• NIPT is an advanced screening test, not a diagnostic test. An invasive prenatal test is required to confirm all high-chance NIPT results. This is because, rarely, the placental cfDNA will not be representative of the fetal genome owing to confined placental mosaicism (CPM). In CPM, the aneuploid cells are present in the placenta but not in the fetus. This can lead to a false positive NIPT result.
• It is not available in triplet or higher multiple pregnancies.
• It is not available to pregnant women who have features that may interfere with testing, for example Down syndrome, a balanced chromosomal translocation, or cancer (as the tumour may release cfDNA).
• It is not available to women who have had an organ transplant or a recent (less than four months ago) blood transfusion.

• A quantity of 20ml of pregnant patient blood is required in cell-stabilising blood tubes (Streck or PAXgene).
• The minimum gestation is from 11 weeks.
• Testing must be arranged in advance through your local antenatal clinic or fetal medicine unit.
• Results are normally available within 10 days of blood draw.

• NIPT is used to screen for common fetal aneuploidies in a way that is not invasive to the pregnancy so does not have the associated small risk of miscarriage.
• The test is performed on cell-free DNA that is extracted from a maternal blood sample, this contains both maternal and fetal DNA.
• It is possible to identify which chromosome each isolated fragment of DNA comes from. By looking at the proportions of fragments derived from each chromosome, it can be determined whether there is an excess of fragments from any particular chromosome.

For clinicians

• Gov.uk guidance: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome: NIPT
• NHS Fetal Anomaly Screening Programme: NIPT E-learning unit
• Royal College of Obstetricians and Gynaecologists (RCOG): Care after non-invasive pre-natal testing

References:

• Navaratnam K, Alfirevic Z. ‘Amniocentesis and chorionic villus sampling‘. British Journal of Obstetrics and Gynaecology 2022: volume 129, issue 1, pages e1–e15. DOI: 10.1111/1471-0528.16821

For patients

• Gov.uk guidance: Down’s syndrome, Edwards’ syndrome and Patau’s syndrome
• Gov.uk guidance: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome: NIPT
• Gov.uk guidance: Your choices after a higher-chance screening result
• Parent and family support: Down’s Syndrome Association
• Parent and family support: Soft UK
• Parent and family support: Positive About Down Syndrome
• Patient support: Antenatal Results and Choices