Guidance

Prenatal diagnosis

Updated 16 December 2024

Applies to England

For naming conventions used throughout this guidance and other general information, please see the handbook overview.

Women are offered and can choose to have prenatal diagnosis (PND) in the following 2 situations:

• a higher chance result for trisomy 21 (T21), trisomy 18 (T18) or trisomy 13 (T13) (see sections 4.1, 4.2 and 4.3 in the handbook overview) from the NHS combined or quadruple test or non-invasive prenatal testing (NIPT)
• unexpected structural findings on the 20-week screening scan

The PND procedure should be made available to the woman before or on 3 working days from receipt of higher chance combined or quadruple test results.

In this guidance, PND refers to chorionic villus sampling (CVS) and amniocentesis. These procedures should only be performed by specially trained healthcare professionals. Women may be required to attend a tertiary-level centre.

CVS is a transabdominal or sometimes transcervical procedure performed under continuous ultrasound guidance. It is usually performed from 11 to 14 weeks of pregnancy but can be done later. A sample of placental tissue is obtained for chromosomal or genetic analysis.

Amniocentesis is a procedure performed under continuous ultrasound guidance. It is usually performed from 15 to 20 weeks of pregnancy but can be done later. A sample of amniotic fluid is obtained for chromosomal or genetic analysis.

One in 200 women who have a CVS or amniocentesis will miscarry.

1. Quantitative fluorescence polymerase chain reaction (QF-PCR) testing

Samples from CVS and amniocentesis procedures are sent to the genomic laboratory for QF-PCR testing. QF-PCR testing detects the evidence of T21, T18 and T13.

QF-PCR testing is based on the amplification of chromosome-specific deoxyribonucleic acid (DNA) sequences. The amplified DNA segments can be visualised and quantified as peak areas on automated scanners.

Women should be informed of the usual reporting time for QF-PCR results before the PND procedure.

Diagnosis/intervention standard FASP-S03 outlines test turnaround timeframes for PND.

2. QF-PCR results

A baby without T21, T18 or T13 may be visualised as having 2 informative peak areas. This is known as 1:1 peak ratio.

A baby with T21, T18 or T13 may be visualised either as having:

• an extra peak, known as tri-allelic ratio
• a 2:1 peak ratio, known as a bi-allelic ratio

3. PND following a higher chance result from the combined or quadruple test or NIPT

For most women, the QF-PCR result will be accurate for both CVS and amniocentesis.

The presence of a tri-allelic T21, T18 or T13 result indicates the chromosomal condition was present at conception and reflects the genotype of the baby.

A bi-allelic T21, T18 or T13 QF-PCR result from a CVS sample may indicate the presence of confined placental mosaicism (CPM). This is a very rare occurrence, less than 0.5% of all CVS samples. CPM is the presence of a chromosomal condition in the placenta that is not present in the baby. Laboratory protocols minimise the risk of CPM from a CVS sample.

Where CPM is suspected, the laboratory will perform further testing to interpret the initial QF-PCR result. This may be a karyotype to count the chromosomes or a further QF-PCR on cultured cells.

There are 2 possible scenarios if the laboratory reports a bi-allelic T21, T18 or T13 QF-PCR result from a CVS sample indicating CPM.

3.1 Scenario 1

T21, T18 or T13 is suspected with findings on ultrasound scan consistent with any of these conditions.

In this scenario, healthcare professionals should discuss pregnancy options with the woman, as further testing is not always required.

3.2 Scenario 2

T21, T18 or T13 is suspected with no unexpected findings on ultrasound scan consistent with any of these conditions.

In this scenario, further testing on cultured cells is performed to interpret the initial QF-PCR result. This is to exclude the possibility of CPM. The offer of a further invasive test (amniocentesis) may be recommended after the analysis of the cultured cells.

Results from the cultured cells must be received and discussed with the woman before any decisions are made regarding pregnancy options including continuing or terminating the pregnancy.

3.3 Future pregnancies

Following a QF-PCR result that shows evidence the baby has T21, T18 or T13, a karyotype test may also be performed. This is to give parents information about the chance of having another baby with one of these conditions. In this situation, decisions about the current pregnancy do not need to be delayed until the karyotype test results are known.

4. PND following unexpected structural findings on the 20-week screening scan

There are 2 clinical management options depending on the QF-PCR result.

4.1 Scenario 1

QF-PCR result indicates T21, T18 or T13.

In this case, healthcare professionals should discuss pregnancy options with the woman including continuing or terminating the pregnancy.

4.2 Scenario 2

QF-PCR result does not indicate T21, T18 or T13.

In this case, management of ongoing diagnostic investigations is not within the remit of the NHS FASP. Local guidance should be in place, for example, use of microarray or (R21) prenatal exome testing with a fetal anomaly gene panel in line with Association of Clinical Genomic Science (ACGS) best practice guidelines and the NHS National Genomic Test Directory.

5. Prenatal diagnosis results

All providers should have written guidance for the communication of PND results. The process for communicating PND results should be discussed and agreed with the woman before the procedure.

All women must be informed of the CVS or amniocentesis result by an appropriately trained healthcare professional.

When a CVS or amniocentesis is performed at a tertiary-level centre, that centre should provide written results to the referring healthcare professional. The woman should be informed of PND results as per local guidelines.

Diagnosis/intervention standard FASP-S03 outlines expected test turnaround times for PND results.

5.1 When PND results show the baby does not have a condition screened for

The woman should be informed of the result and continue with antenatal care. The outcome of the pregnancy should be reported to National Congenital And Rare Diseases Registration Service (NCARDRS).

5.2 When PND results show the baby has a condition screened for

A discussion of the results with an appropriately trained healthcare professional should be offered. Women should be supported to make personal informed choices about their ongoing care and pregnancy options. See section 3 of the handbook overview.

6. Pregnancy outcome audit

Royal College of Obstetricians and Gynaecologists (RCOG) guidelines recommend every department performing CVS and amniocentesis should maintain a register of procedures performed and the pregnancy outcome.

For audit purposes, pregnancy outcome forms should be completed and returned to the screening laboratory, or the locally agreed collating centre for all suspected and confirmed conditions. This should be done at the end of the pregnancy. Providers should develop a pathway for the completion and return of pregnancy outcome forms to the centre collecting the data.

Outcome information should be reported to NCARDRS for quality and monitoring of the NHS FASP.