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SMFM Consult Series #57: Evaluation and management of soft ultrasound markers for aneuploidy

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Contemporary OB/GYN Journal, Vol 67 No 4, Volume 67, Issue 4

Strategic Alliance Partnerships | <b>The Society for Maternal-Fetal Medicine</b>

In this consult series, experts from SMFM discuss the evaluation and management of soft ultrasound markers for aneuploidy.

Soft markers are minor ultrasound findings identified in the midtrimester that commonly do not represent a structural abnormality. These may be normal variants but are noteworthy because of their association with an increased aneuploidy risk. Commonly identified soft markers include echogenic intracardiac focus; echogenic bowel; choroid plexus cyst(s); single umbilical artery; urinary tract dilation; shortened humerus, femur, or both; thickened nuchal fold; and absent or hypoplastic nasal bone1-4 (Table 1).

Contemporaneously with the advancement in aneuploidy detection with soft markers was the development of improved serum screening methods to predict aneuploidy risk.5,6 The introduction of cell-free DNA (cfDNA) techniques greatly improved the ability to screen for common aneuploidies. Given the high sensitivity and specificity of cfDNA for trisomies 21, 18, and 13 across all age groups, in 2020, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine endorsed the option of cfDNA screening for all patients.6

Q| What is the initial approach when an isolated soft marker is identified?

“Isolated” is a soft marker that has been identified in the absence of any fetal structural anomaly, growth restriction, or additional soft marker, following a detailed obstetrical ultrasound examination. Identification of a soft marker is an indication for a detailed obstetrical ultrasound examination (Current Procedural Terminology code 76811) to ensure the finding is isolated.

The decision to perform a detailed examination should be made through a shared decision-making framework. In the case of multiple soft markers or structural abnormalities, the approach to evaluation should be individualized.

If an isolated soft marker is confirmed, subsequent evaluation and counseling depend on prior aneuploidy screening results, additional risk factors for aneuploidy, and associations with nonaneuploid conditions.

Traditionally, the presence or absence of specific soft markers was used to modify the probability of trisomy 21 and 18 for high-risk patients.7

However, the relative importance of this approach has evolved rapidly with improved prenatal screening techniques.

The detection rates for aneuploidy with commonly employed serum screening strategies (ie, first-trimester screen, integrated screen, sequential screen, contingent screen, or quad screen) are high.

cfDNA is the single best screening test for the common trisomies (trisomies 21, 18, and 13), and the posttest probability of a common aneuploidy after negative cfDNA screening is very low.8 Although a range of positive likelihood ratios (LRs) for a particular aneuploidy exists for each soft marker, even when the highest positive LRs are applied to a population that has previously had a negative cfDNA result, the risk of trisomy 21 is negligibly affected.

Only diagnostic testing removes residual risk for aneuploidy detection.

Thus, a patient may elect diagnostic testing for any indication. However, we do not recommend diagnostic testing for aneuploidy solely for the evaluation of an isolated soft marker following a negative serum or cfDNA screening result (grade 1B).

Similarly, if a pregnant person has undergone diagnostic testing and the results indicate a normal karyotype, identification of a soft marker is insignificant with regard to aneuploidy and should be reported as such.

Some pregnant people may decline any aneuploidy screening following a shared decision-making process that incorporates accurate information, accessible health care resources, and the patient’s clinical context, values, beliefs, and potential anxiety created by the identification and discussion of a soft marker.6,9,10

Each practice should establish a standardized protocol for how the identification of an isolated soft marker will be documented and managed for patients who have previously declined aneuploidy screening.

These protocols should ensure patients are informed prior to the ultrasound examination of how findings will be handled to enhance shared decision-making and patient autonomy.

Q|What is the counseling and management regarding soft ultrasound markers?

Table 1 summarizes the definition, prevalence, range of LRs, evaluation, and follow-up for commonly identified soft markers. Table 2 summarizes recommendations for the evaluation and management of isolated soft ultrasound markers for aneuploidy in the
second trimester.

References

  1. Benacerraf BR, Frigoletto FD Jr, Cramer DW. Down syndrome: sonographic sign for diagnosis in the second-trimester fetus. Radiology. 1987;163(3):811-813. doi:10.1148/radiology.163.3.2953039
  2. Benacerraf BR, Gelman R, Frigoletto FD Jr. Sonographic identification of second-trimester fetuses with Down’s syndrome. N Engl J Med. 1987;317(22):1371-1376. doi:10.1056/NEJM198711263172203
  3. Benacerraf BR, Mandell J, Estroff JA, Harlow BL, Frigoletto FD Jr. Fetal pyelectasis: a possible association with Down syndrome. Obstet Gynecol. 1990;76(1):58-60.
  4. Lockwood C, Benacerraf B, Krinsky A, et al. A sonographic screening method for Down syndrome. Am J Obstet Gynecol. 1987;157(4 Pt 1):803-808. doi:10.1016/s0002-9378(87)80059-5
  5. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down’s syndrome. N Engl J Med. 2005;353(19):2001-2011. doi:10.1056/NEJMoa043693
  6. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for fetal chromosomal abnormalities: ACOG practice bulletin, number 226. Obstet Gynecol. 2020;136(4):e48-e69. doi:10.1097/AOG.0000000000004084
  7. Nyberg DA, Luthy DA, Resta RG, Nyberg BC, Williams MA. Age-adjusted ultrasound risk assessment for fetal Down’s syndrome during the second trimester: description of the method and analysis of 142 cases. Ultrasound Obstet Gynecol. 1998;12(1):8-14. doi:10.1046/j.1469-0705.1998.12010008.x
  8. Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017;50(3):302-314. doi:10.1002/uog.17484
  9. Filly RA. Obstetrical sonography: the best way to terrify a pregnant woman. J Ultrasound Med. 2000;19(1):1-5. doi:10.7863/jum.2000.19.1.1
  10. Filly RA, Norton ME. Obstetric sonography: why are we still terrifying pregnant women? J Ultrasound Med. 2018;37(9):2277-2278. doi:10.1002/jum.14572