Nuchal translucency

A nuchal translucency (NT), also called nuchal fold or nuchal thickness, is a measurable area at the back of the fetal neck. It is examined using ultrasound as part of combined screening.

A small amount of fluid (up to 3.5mm) within the nuchal space (between the back of the neck and the skin) is normal. Excess fluid can also be a feature in a normal fetus; however, it may be indicative of a chromosomal, syndromic, structural or genetic condition.

NT is examined using ultrasound as part of combined screening for Down, Edwards and Patau syndromes from 11 to 13+6 weeks of pregnancy.

To measure the NT, the fetal crown-rump length should be between 45mm and 84mm.

Up to 3.5mm of fluid within the nuchal space is normal. Excess fluid can also be a feature in a normal fetus; however, it may be indicative of a chromosomal, syndromic, structural or genetic condition.

There are many potential causes of a higher NT measurement. These include:

• congenital heart conditions
• genetic conditions such as Turner syndrome, Noonan syndrome and trisomies 21, 18 and 13;
• viral infection;
• fetal anaemia; and
• lymphatic anomalies.

The likelihood of underlying pathology increases as nuchal thickness increases.

Table 1: Higher NT measurements and associated risks

NT screening can detect around 80% of fetuses with Down syndrome and other major aneuploidies for a false positive rate of 5%. It is rarely used in isolation, however; rather, it is typically combined with serum markers for increased screening accuracy.

The chance of an underlying genetic cause increases with increasing nuchal thickness. Genomic testing in this setting can identify an underlying cause. Identification of an underlying cause can provide prognostic information, which can inform decision-making and clinical management.

Any pregnancy with an NT above 3.5mm should be offered genomic testing to look for an underlying cause. To enable testing, a DNA sample will need to be obtained from the fetus. This can be achieved through invasive prenatal testing via chorionic villus sampling or amniocentesis, or through non-invasive prenatal testing (NIPT), which involves taking a blood sample from the pregnant woman. There are advantages and disadvantages to each of these methods. For example, invasive testing is associated with a small risk of miscarriage; however, it is also associated with a slightly increased accuracy rate.

The type of genomic testing available depends on the degree of NT and any associated features. For isolated, mildly increased NT, common aneuploidy testing is available and tests for trisomies 21, 18 and 13. For more severely increased NTs, especially when associated with additional anomalies, fetal exome sequencing may be available in addition to common aneuploidy testing. For more information, please see Fetus with raised nuchal translucency.

Recurrence risk is dependent on the underlying genetic or chromosomal cause. If no cause is identified and the baby is born healthy, the recurrence risk in a subsequent pregnancy is low but slightly above the baseline risk.

If a trisomy (such as Down, Edwards or Patau syndrome) is identified, the recurrence risk is likely to be low as most cases are caused by nondisjunction (an error in cell division in which chromosomes fail to separate properly during the creation of the egg or sperm). However, trisomies can occasionally arise from balanced structural chromosomal rearrangements in parents – for example, reciprocal chromosome translocations or Robertsonian chromosome translocations. In such cases, the recurrence risk can be substantially higher, and additional reproductive options are often available; these patients should be referred for tailored genomic counselling. Genomic laboratories can help advise clinicians regarding the need for parental testing for underlying structural rearrangements.

When a trisomy arises from nondisjunction, the recurrence risk is slightly raised compared to the baseline, and non-invasive testing is available. For more information, please see Pregnant woman with a previous pregnancy or baby diagnosed with full trisomy 21, 18 or 13.

If a single gene cause such as Noonan syndrome is identified, the recurrence risk depends on whether a parent is also affected. As symptoms can be mild, the absence of a known diagnosis should not be relied on and parental testing should be offered.

• Noonan syndrome is an autosomal dominant condition. Individuals affected by an autosomal dominant condition have one working copy of the gene, and one with a pathogenic variant.
• The chance of a child inheriting the gene with the variant from an affected parent is 1 in 2 (50%).
• Incomplete penetrance can occur (that is, not everyone who has the variant develops the disease).
• Reproductive options are available and genomic counselling should be offered.
• If both parents are unaffected, the recurrence risk is much lower; however, it is still above baseline due to the possibility of germline (gonadal) mosaicism, which confers a 1%–2% risk. Parents may opt for testing in a subsequent pregnancy.

If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Prenatal management will depend on the degree of increased NT and the presence/absence of associated anomalies. Patients are typically referred to fetal medicine for ongoing management.

Causes such as infection, fetal anaemia and congenital heart disease will need to be considered and investigated. Monitoring of the NT via serial ultrasound scan is required to see if it resolves, progresses or remains stable, and to see if any other anomalies become apparent. These factors will help guide further management in affected pregnancies.

For clinicians

• NHS England: National Genomic Test Directory
• The Fetal Medicine Foundation: Nuchal translucency scan

For patients

• Antenatal Results & Choices
• International Society of Ultrasound in Obstetrics and Gynaecology: Nuchal translucency