SMFM Guidance – The Role of Prenatal Ultrasound and NIPT 

SUMMARY:

SMFM has released, as part of their Consult Series, a document on the role of prenatal ultrasound in the context of cfDNA screening.  The summary recommendations are as follows:

• Negative cfDNA at 11-14 weeks: (evidence level 1B)
  • First trimester ultrasound only for NT measurement not recommended
• Negative cfDNA and isolated ‘soft marker’: (evidence level 2B)
  • Diagnostic testing is not recommended solely for this indication
  • Describe ‘soft marker’ finding as ‘not clinically significant’ or ‘normal variant’
• Negative 1st or 2nd trimester screen and isolated ‘soft marker’: (evidence level 2B)
  • Describe ‘soft marker’ finding as ‘not clinically significant’ or ‘normal variant’
• Structural abnormality on ultrasound (evidence level 1A)
  • Offer diagnostic testing using microarray
• Do not offer routine screening for microdeletions using cfDNA (evidence level 1B)

Key Points:

• Examples of  ‘soft marker’ include echogenic intracardiac focus or choroid plexus cysts
• ‘Isolated’ implies a single finding and the absence of any other pathology
• If multiple ‘soft markers’ are identified
  • Refer for genetic counseling, consideration of diagnostic testing
  • prenatal risk assessment should be limited to expert centers and individuals

Levels of Evidence:

• 1A: Strong recommendation; high-quality evidence
• 1B: Strong recommendation; moderate-quality evidence
• 2B: Weak recommendation; moderate-quality evidence

Learn More – Primary Sources:

SMFM Consult Series #42: The role of ultrasound in women who undergo cell-free DNA screening

SMFM Consult Series 74: Cell‐free DNA screening for aneuploidies: Updated guidance

ACOG Committee Opinion 682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology

ACOG Practice Bulletin 162: Prenatal Diagnostic Testing for Genetic Disorders

ACOG Practice Bulletin 175: Ultrasound in Pregnancy

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Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

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Nuchal Translucency – First Trimester Measurement

WHAT IS IT?

Nuchal translucency (NT) is a fluid-filled space normally seen behind the fetal neck on ultrasound performed in the first trimester of pregnancy

• A precise measurement of this space is used in first trimester aneuploidy screening in combination with levels of maternal serum markers [free or total hCG and pregnancy-associated plasma protein A (PAPP-A)] to provide an adjusted risk for fetal aneuploidy
• Measurements should be performed between 11w0d and 13w6d weeks of pregnancy
  • ISPD suggests 12 weeks may be superior because
    • Patient scheduling may be easier and fetal anatomic visualization is better compared to 11 weeks
    • Screening performance is superior compared to 13 weeks
• Determination of whether or not a measurement is normal requires an accurate measurement of fetal size using a crown rump length (CRL) measurement
• Programs exist for credentialing purposes to provide education and ongoing mechanism for quality review and is a necessary requirement for optimal screening performance

KEY POINTS:

A fetal measurement >3.0 mm is an independent risk factor for fetal abnormalities and requires referral and further follow up

• More commonly associated with aneuploidies such as Down syndrome and Turner syndrome, but may also be associated with other genetic syndromes, such as skeletal dysplasias
  • Larger NT may be associated with Noonan syndrome, especially in the context of other structural anomalies such as cardiac and renal findings
  • Approximately 10% risk with NT >3.0 mm and normal chromosomal complement
• Fetal structural anomalies, including cardiac, abdominal wall and diaphragmatic defects, must be assessed by anatomical fetal ultrasound and fetal echocardiography
• If the NT is sufficiently large to extend the length of the fetus with visible septations, this is called a ‘cystic hygroma’ and risk of aneuploidy is 50% (see ‘Related ObG Topics’ below)
• Other genetic syndromes and structural anomalies may be present even in those with normal karyotype
  • normal outcome may be <20%
• Refer for high risk OB consultation and genetic counseling, and consider prenatal diagnostic testing
  • ACOG guidance recommends offering invasive testing using microarray in the setting of fetal structural anomalies seen on prenatal ultrasound
• ISUOG recommends that “Sonographic assessment and measurement of NT should be part of the screening protocol, independent of whether it is used for risk assessment for aneuploidy.”

Learn More – Primary Sources:

SMFM Consult Series 74: Cell‐free DNA screening for aneuploidies: Updated guidance 

Fetal Medicine Foundation: Nuchal Translucency Scan

ISUOG Practice Guidelines (updated): performance of 11–14‐week ultrasound scan

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings

Position Statement from the Chromosome Abnormality Screening Committee on Behalf of the Board of the International Society for Prenatal Diagnosis

Testing for Noonan Syndrome after Increased Nuchal Translucency

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist:

Maternal-Fetal Medicine Specialist Locator-SMFM