Non-invasive prenatal testing (NIPT)

Non-invasive prenatal testing (NIPT) is a method used to screen for common fetal aneuploidies. By looking at cell-free DNA (cfDNA) proportions circulating in the expectant mother’s blood, clinicians can determine if there is an excess of chromosome-derived DNA fragments. Being a blood-based test, it is non-invasive to the pregnancy so it doesn’t present a miscarriage risk. Currently, NIPT is available on the NHS via the Fetal Anomaly Screening Programme and via the R445 pathway. It must be arranged in advance through local pathways.

In 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 Down syndrome (trisomy 21), Edward syndrome (trisomy 18) and Patau syndrome (trisomy 13). 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 is because both maternal and placental DNA may be found outside of cells – where it is termed cell-free DNA (cfDNA) – such as in plasma. 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 massively parallel 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 available on the NHS via the Fetal Anomaly Screening Programme and via the R445 pathway.
• 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, stem cell therapy or a recent (less than four months ago) blood transfusion.

• Requesting NIPT may be done in the following scenarios:
  • via the Fetal Anomaly Screening Programme (FASP) for women who have had a screening test result (either via the NHS combined first-trimester screening NHS combined or NHS quadruple screening test) that suggests there is a high chance of fetal trisomy.
  • via the R445 pathway for women with a history of a pregnancy or child diagnosed with full trisomy 21, 18 or 13. See Presentation: Pregnancy where previous pregnancy or child diagnosed with trisomy 21, 18 or 13.
• The eligibility criteria may vary according to whether NIPT is offered via the FASP or R445 pathway. Always check the National Genomic Test Directory for latest eligibility criteria.
• For NIPT offered after a high chance screening result on the FASP pathway, the minimum gestation is from 11 weeks.
• For NIPT offered on the R445 pathway, the minimum gestation is from 10+0 weeks.
• A quantity of 20ml of the pregnant woman’s blood is required in cell-stabilising blood tubes (Streck or PAXgene).
• 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: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome: NIPT (guidance)
• NHS England: National Genomic Test Directory
• NHS Fetal Anomaly Screening Programme: Non Invasive Prenatal Testing – evaluative roll out (an eLfH-based resource)
• Royal College of Obstetricians and Gynaecologists (RCOG): Care after non-invasive pre-natal testing

References:

• Navaratnam K and 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: Down’s syndrome, Edwards’ syndrome and Patau’s syndrome (guidance)
• Gov.uk: Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome: NIPT (guidance)
• Gov.uk: Your choices after a higher-chance screening result (guidance)
• Down’s Syndrome Association
• Soft UK (support for families of children born with trisomy 13 or trisomy 18)
• Positive About Down Syndrome
• Antenatal Results and Choices (support for expectant parents)