Evaluation and management of soft ultrasound markers for aneuploidy

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

Along with advances in the detection of aneuploidy with soft markers, improved serum screening methods have been developed to predict the risk of aneuploidy.5.6 The introduction of cell-free DNA (cfDNA) techniques has greatly improved the ability to screen for common aneuploidies. Given the high sensitivity and specificity of cfDNA for trisomies 21, 18 and 13 in all age groups, in 2020 the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine approved the cfDNA screening option for all patients.6

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

“Isolated” is a soft marker that has been identified in the absence of any fetal structural abnormality, 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 that the finding is isolated.

The decision to conduct a detailed review should be made within a shared decision-making framework. In the case of multiple soft markers or structural abnormalities, the assessment approach should be individualized.

If an isolated weak marker is confirmed, further evaluation and counseling depends on previous aneuploidy screening results, additional risk factors for aneuploidy, and associations with non-aneuploid conditions.

Traditionally, the presence or absence of specific soft markers was used to alter the likelihood of trisomy 21 and 18 in high-risk patients.7

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

Aneuploidy detection rates with commonly used serum screening strategies (ie, first-trimester screening, integrated screening, sequential screening, contingent screening, or quadruple screening) are high.

The cfDNA is the best screening test for common trisomies (trisomies 21, 18 and 13), and the post-test probability of common aneuploidy after a negative cfDNA screen is very low.8 Although there is a range of positive likelihood ratios (LRs) for a particular aneuploidy 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 negligible.

Only diagnostic tests eliminate the residual risk of detecting aneuploidy.

Thus, a patient can choose a diagnostic test for any indication. However, we do not recommend the diagnostic test 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, the identification of a soft marker is insignificant with respect 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 clinical context, values, beliefs, and anxiety. potential of the patient created by the identification and discussion of a fuzzy marker.6,9,10

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

These protocols should ensure that patients are informed before the ultrasound examination how the results will be handled in order to enhance shared decision-making and patient autonomy.

Q|What is the advice and support for soft ultrasound markers?

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

The references

  1. Benacerraf BR, Frigoletto FD Jr, Cramer DW. Down syndrome: ultrasound 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 syndrome. N English 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. An ultrasound 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 syndrome. N English J med. 2005;353(19):2001-2011. doi:10.1056/NEJMoa043693
  6. American College of Obstetricians and Gynecologists Practice Bulletin Committee—Obstetrics; Genetics Committee; Maternal-Fetal Medicine Society. Screening for fetal chromosomal abnormalities: ACOG practice bulletin, issue 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 trisomy 21 in 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. Obstetric ultrasound: 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 ultrasound: why do we still scare pregnant women? J Ultrasound Med. 2018;37(9):2277-2278. doi:10.1002/jum.14572

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