What is the significance of an increased Nuchal Translucency (NT) scan with Non-Invasive Prenatal (NIP) testing?

From the Guidelines

An increased Nuchal Translucency (NT) scan with Non-Invasive Prenatal (NIP) testing is a significant marker for fetal aneuploidy, genetic syndromes, structural anomalies, and intrauterine demise, and therefore, requires careful evaluation and follow-up diagnostic testing. The NT scan measures the fluid collection at the back of the baby's neck using ultrasound, and an absolute threshold value of 3 mm is considered uniformly increased at any crown-rump length between 11 and 14 weeks 1. According to a study published in the Journal of the American College of Radiology, an increased NT thickness is associated with a 10-fold increase in chromosomal abnormalities such as trisomies, Turner syndrome, and triploidy 1.

Key Points to Consider

• The American College of Medical Genetics and Genomics (ACMG) recommends Non-Invasive Prenatal Screening (NIPS) for all pregnant individuals over traditional screening for common trisomies and single chromosome abnormalities (SCAs) 1.
• NIPS has been shown to have superior screening characteristics, including higher detection rates and fewer false positives than traditional screening methods 1.
• The introduction of NIPS into clinical practice has resulted in a dramatic reduction of invasive diagnostic testing, and patients view the ability to have a reliable and accurate screen as a significant benefit 1.

Clinical Implications

• All pregnant women should undergo NIPS, ideally performed between 11-14 weeks of pregnancy, to screen for chromosomal abnormalities.
• The NT scan should be performed in conjunction with NIPS to provide a comprehensive screening and evaluate the baby's anatomy, heart, and placental position.
• If results indicate increased risk, follow-up diagnostic testing, such as amniocentesis, should be recommended to confirm the diagnosis and provide parents with informed decisions about their pregnancy.

From the Research

Significance of Increased Nuchal Translucency (NT) Scan

The significance of an increased Nuchal Translucency (NT) scan with Non-Invasive Prenatal (NIP) testing can be understood through the following points:

• An increased NT thickness of ≥ 3.5 mm is a well-established marker for congenital anomalies and adverse pregnancy outcome between 11 and 14 weeks' gestation 2
• Fetuses with an early increased NT thickness are at considerable risk of an adverse pregnancy outcome, even if the NT normalizes after 11 weeks 2
• Non-invasive prenatal testing (NIPT) is a highly accurate technique that uses maternal serum, but it has limitations in detecting microdeletions/microduplications (MD) or triploidy 3
• Nuchal translucency (NT) measurement can be used to detect genetic abnormalities not identified by genome-wide NIPT, but its utility is limited 3

Management of Increased NT with Low-Risk NIPT Result

The management of pregnancies with a low-risk NIPT result and an isolated increased NT measurement is a dilemma for clinicians, and the following points should be considered:

• The optimal management of such pregnancies is not well-established, and clinicians should navigate the uncertainty with parents 4
• Parents should be informed about the potential risks and limitations of NIPT and NT measurement, and the need for further testing and follow-up 4
• Invasive prenatal testing should be offered if an increased NT of ≥ 2.5 mm is observed before 11 weeks' gestation 2
• Expectant parents should be referred to a fetal medicine unit for detailed ultrasonography, regardless of the NT measurement 2

Detection of Genetic Abnormalities

The detection of genetic abnormalities using NT measurement and NIPT can be understood through the following points:

• A total of 73 genetic abnormalities were detected in a study of 324 pregnant women with fetal NT > 95th centile and below 99th centile, including 45 cases of chromosomal aneuploidy, 7 cases of structural abnormalities, and 21 cases of copy number variations (CNVs) 5
• The detection rate of NIPT was 3.79% in a study of 211 pregnant women with fetal isolated increased NT > 95th centile and below 99th centile 5
• Enlarged NT measurement is a poor predictor of genetic abnormalities not identified by genome-wide NIPT, with a low positive predictive value (PPV) 3