marcadores2trimestre

SMFM Consult Series
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Society for Maternal-Fetal Medicine
Consult Series #57: Evaluation and
management of isolated soft ultrasound
markers for aneuploidy in the second trimester
(Replaces Consults #10, Single umbilical artery, October 2010; #16, Isolated echogenic
bowel diagnosed on second-trimester ultrasound, August 2011; #17, Evaluation and
management of isolated renal pelviectasis on second-trimester ultrasound, December
2011; #25, Isolated fetal choroid plexus cysts, April 2013; #27, Isolated echogenic
intracardiac focus, August 2013)
Society for Maternal-Fetal Medicine (SMFM); Malavika Prabhu, MD; Jeffrey A. Kuller, MD; and Joseph R. Biggio, MD, MS
Soft markers were originally introduced to prenatal ultrasonography to improve the detection of trisomy 21 over that achievable with
age-based and serum screening strategies. As prenatal genetic screening strategies have greatly evolved in the last 2 decades, the
relative importance of soft markers has shifted. The purpose of this document is to discuss the recommended evaluation and
management of isolated soft markers in the context of current maternal serum screening and cell-free DNA screening options. In this
document, “isolated” is used to describe 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. In this document, “serum screening
methods” refers to all maternal screening strategies, including first-trimester screen, integrated screen, sequential screen, contingent
screen, or quad screen. The Society for Maternal-Fetal Medicine recommends the following approach to the evaluation and management of isolated soft markers: (1) we do not recommend diagnostic testing for aneuploidy solely for the evaluation of an isolated
soft marker following a negative serum or cell-free DNA screening result (GRADE 1B); (2) for pregnant people with no previous
aneuploidy screening and isolated echogenic intracardiac focus, echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive
aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1B); (3) for pregnant
people with no previous aneuploidy screening and isolated thickened nuchal fold or isolated absent or hypoplastic nasal bone, we
recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening
through cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive or diagnostic testing via amniocentesis,
depending on clinical circumstances and patient preference (GRADE 1B); (4) for pregnant people with no previous aneuploidy
screening and isolated choroid plexus cysts, we recommend counseling to estimate the probability of trisomy 18 and a discussion of
options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive
(GRADE 1C); (5) for pregnant people with negative serum or cell-free DNA screening results and an isolated echogenic intracardiac
focus, we recommend no further evaluation as this finding is a normal variant of no clinical importance with no indication for fetal
echocardiography, follow-up ultrasound imaging, or postnatal evaluation (GRADE 1B); (6) for pregnant people with negative serum or
cell-free DNA screening results and isolated fetal echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we
recommend no further aneuploidy evaluation (GRADE 1B); (7) for pregnant people with negative serum screening results and isolated
thickened nuchal fold or absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and
discussion of options for no further aneuploidy evaluation, noninvasive aneuploidy screening through cell-free DNA, or diagnostic
testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (8) for pregnant people with
negative cell-free DNA screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend no
further aneuploidy evaluation (GRADE 1B); (9) for pregnant people with negative serum or cell-free DNA screening results and isolated
choroid plexus cysts, we recommend no further aneuploidy evaluation, as this finding is a normal variant of no clinical importance with
no indication for follow-up ultrasound imaging or postnatal evaluation (GRADE 1C); (10) for fetuses with isolated echogenic bowel, we
recommend an evaluation for cystic fibrosis and fetal cytomegalovirus infection and a third-trimester ultrasound examination for
reassessment and evaluation of growth (GRADE 1C); (11) for fetuses with an isolated single umbilical artery, we recommend no
additional evaluation for aneuploidy, regardless of whether results of previous aneuploidy screening were low risk or testing was
declined. We recommend a third-trimester ultrasound examination to evaluate growth and consideration of weekly antenatal fetal
surveillance beginning at 36 0/7 weeks of gestation (GRADE 1C); (12) for fetuses with isolated urinary tract dilation A1, we recommend
an ultrasound examination at 32 weeks of gestation to determine if postnatal pediatric urology or nephrology follow-up is needed.
For fetuses with urinary tract dilation A2-3, we recommend an individualized follow-up ultrasound assessment with planned postnatal
follow-up (GRADE 1C); (13) for fetuses with isolated shortened humerus, femur, or both, we recommend a third-trimester ultrasound
examination for reassessment and evaluation of growth (GRADE 1C).
Key words: aneuploidy assessment, aneuploidy screening, cell-free DNA screening, serum markers, soft
markers, ultrasound
Corresponding author: Society for Maternal-Fetal Medicine: Publications Committee. [email protected]
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Introduction
Soft ultrasound markers were initially described as a
screening method for trisomy 21 to improve the detection
rate (DR) over that based on age-related risk alone. Soft
markers are minor ultrasound findings identified in the midtrimester of pregnancy that most commonly do not represent
a structural abnormality and may be normal variants but are
noteworthy because of their association with an increased
aneuploidy risk. Commonly identified soft markers
addressed in this document include echogenic intracardiac
focus (EIF); echogenic bowel, choroid plexus cysts (CPCs);
single umbilical artery (SUA); urinary tract dilation (UTD);
shortened humerus, femur, or both; thickened nuchal fold;
and absent or hypoplastic nasal bone (Table 1).1e4 Several
other ultrasound findings associated with trisomy 21 include
mild ventriculomegaly, clinodactyly, and sandal gap deformity that are not addressed in this document.5
Concomitant with the advancement in aneuploidy
detection with soft markers was the development of
improved serum screening methods to predict aneuploidy
risk, including second-trimester quad screening and firsttrimester screening with maternal serum analytes and
nuchal translucency (NT) measurement.6,7 In 2011, the
introduction of cell-free DNA (cfDNA) techniques greatly
improved the ability to screen for common aneuploidies.
Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and the Society for
Maternal-Fetal Medicine (SMFM) state that screening
(serum screening with or without NT ultrasound examination
or cfDNA screening) and diagnostic testing (chorionic villus
sampling or amniocentesis) for chromosomal abnormalities
should be discussed and offered to all patients early in
pregnancy regardless of maternal age or baseline risk.7
Historically, testing was offered only to patients considered
at high risk because of maternal age or personal or family
history. However, given the personal nature of prenatal
testing decision-making and the inefficiency of offering
testing only to patients at high risk, all patients should be
offered both screening and diagnostic testing options.7
Given the high sensitivity and specificity of cfDNA for trisomies 21, 18, and 13 across all age groups, in 2020, ACOG
and SMFM stated that a patient’s baseline risk should not
limit screening options for chromosomal abnormalities and
endorsed the option of cfDNA screening for all patients.7
The accuracy of cfDNA screening has resulted in the evolution of ultrasound-based screening for aneuploidy.
Several organizations have recommendations on the role of
soft markers in assessing the risk of aneuploidy, including
SMFM, ACOG, the International Society of Ultrasound in
Obstetrics and Gynecology, the National Institute for Health
and Care Excellence, and the Society of Obstetricians and
Gynaecologists of Canada.8e11 The purpose of this document is to focus specifically on the evaluation and management of isolated soft ultrasound markers for aneuploidy
diagnosed in the second trimester of pregnancy. Isolated
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soft ultrasound marker evaluation and management are
discussed both in the context of known results from serum
or cfDNA screening and in patients who have not had
aneuploidy screening. In this document, “isolated” is used
to describe 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. “Serum screening methods” refers
to all maternal screening strategies, including first-trimester
screen, integrated screen, sequential screen, contingent
screen, or quad screen.
What is the initial approach when an isolated
soft marker is identified?
The presence of multiple soft markers or other abnormal
ultrasound findings increases the risk of aneuploidy.12
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 (ie, a single marker that does not co-occur with any
structural abnormality, growth restriction, or additional soft
marker). The option for such evaluation should be discussed
with patients. However, not all patients will desire to proceed with further evaluation, and access to trained providers varies throughout the United States and worldwide.
The decision to perform a detailed examination should be
made through a shared decision-making framework,
incorporating patient preferences, values, and availability of
resources. The discussion and patient’s decision should be
documented in the medical record. 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
will depend on previous aneuploidy screening results;
additional risk factors for aneuploidy, such as age or family
history; and associations with nonaneuploid conditions (eg,
cystic fibrosis or viral infection).
Traditionally, the presence or absence of specific soft
markers was used to modify the probability of trisomy 21 and
secondarily that of trisomy 18 for high-risk patients.13 This
approach requires an accurate assessment of (1) the a priori,
or pretest, risk (age-related risk at the time of delivery or agerelated risk in the midtrimester of pregnancy) of the aneuploidy of interest; (2) the posttest risk based on results of a
screening test, if performed; (3) validated and reproducible
ultrasonographic definitions for the identification of each soft
marker; and (4) accurate estimates of sensitivity and specificity to calculate the positive and negative likelihood ratios
(LRs) of an isolated soft marker for a particular aneuploidy.8,12
Accepted thresholds for positive LRs are as follows: LRs from
approximately 1.5 to 5 confer a small additional increase in
the likelihood of the outcome; LRs between 5 and 10 confer a
moderate additional increase in the likelihood of the outcome;
and LRs of >10 confer a substantial additional increase in the
likelihood of the outcome.
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TABLE 1
Isolated soft markers: Recommended management
Soft marker
Aneuploidy evaluation
Antenatal management
Echogenic intracardiac cfDNA or serum screen negative: none Routine care
focus
No previous screening: counseling
for noninvasive testing for aneuploidy
Follow-up imaging
N/A
Echogenic bowel
cfDNA or serum screen negative: none Evaluation for cystic fibrosis,
congenital viral infection,
No previous screening: counseling
intra-amniotic bleeding
for noninvasive testing for aneuploidy
Third-trimester ultrasound
examination for reassessment
and evaluation of growth
Choroid plexus cyst
cfDNA or serum screen negative: none Routine care
No previous screening: counseling
for noninvasive testing for aneuploidy
N/A
Single umbilical artery
cfDNA or serum screen negative
or no previous screening: none
Urinary tract dilation
cfDNA or serum screen negative: none Evaluation for persistence, with
frequency of evaluation dependent
No previous screening: counseling
on initial findings
for noninvasive testing for aneuploidy
Third-trimester ultrasound examination
to determine whether postnatal pediatric
urology or nephrology follow-up is needed
Shortened humerus,
femur, or both
cfDNA or serum screen negative: none Evaluation for skeletal dysplasias
No previous screening: counseling
for noninvasive testing for aneuploidy
Third-trimester ultrasound
examination for reassessment
and evaluation of growth
Thickened nuchal fold
cfDNA negative: none
Serum screen negative: counseling
for no further testing vs noninvasive
vs invasive testing for aneuploidy
No previous screening: counseling
for noninvasive vs invasive testing
for aneuploidy
Routine care
N/A
Absent or hypoplastic
nasal bone
cfDNA negative: none
Serum screen negative: counseling
for no further testing vs noninvasive
vs invasive testing for aneuploidy
No previous screening: counseling
for noninvasive vs invasive testing
for aneuploidy
Routine care
N/A
Consideration for weekly antenatal
Third-trimester ultrasound
surveillance beginning at 36 0/7 wk examination for evaluation of growth
of gestation
cfDNA, cell-free DNA; N/A, not applicable.
Society for Maternal-Fetal Medicine. SMFM Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester. Am J Obstet
Gynecol 2021.
Although LRs are inherently independent of a priori risk and
disease prevalence, variability in positive and negative LR
estimates exists for several reasons: (1) differences in patient
populations studied, (2) variability in soft marker definitions,
(3) variability in detection of soft markers by ultrasound, and
(4) whether or not, for any isolated soft marker, the lack of
other soft markers (ie, negative LRs) is incorporated into
the positive LR estimate. A final risk estimate incorporating
the presence or absence of an ultrasound soft marker for the
aneuploidy of interest was traditionally calculated to counsel
a patient on the risk of aneuploidy and risks and benefits of
diagnostic testing. However, the relative importance of this
approach has evolved rapidly with improved prenatal
screening techniques.
The widespread introduction of cfDNA screening into
current obstetrical practice has changed the relevance of a
soft marker finding because the posttest probability of a
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common aneuploidy after negative cfDNA screening is very
low.14 For instance, a negative cfDNA result lowers the risk
of trisomy 21 by 300-fold.15 The residual risk of a 35-yearold woman, whose age-related risk of trisomy 21 at delivery
is 1 in 356, is reduced to <1 in 50,000 after a negative cfDNA
result. Although a range of positive LRs 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.
Among patients undergoing first-trimester NT, serum
screening, or both, the DR for trisomy 21 and other aneuploidies and corresponding residual risk after a negative
screening test result depends on the screening paradigm
used.7 cfDNA is the single best screening test for the
common trisomies (trisomies 21, 18, and 13) and results in
the lowest residual risk of aneuploidy. The DRs for aneuploidy with commonly employed serum screening
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strategies are high, ranging from 81% to 99% for trisomy
21.7 Regardless of the screening strategy used, there is no
one threshold value for residual risk above which additional
aneuploidy evaluation is routinely recommended, as risk
estimates represent a continuum and are ultimately predicated on a patient’s interpretation of risk. However, many
laboratories employ a risk cutoff of 1 in 250 or 1 in 300,
above which further evaluation and diagnostic testing are
recommended. Because many soft markers are associated
with minimal or moderate elevations in the risk of aneuploidy, the finding of an isolated soft marker in the presence
of the high negative predictive value of all screening strategies is unlikely to substantially alter the risk estimate
enough to warrant a recommendation for diagnostic testing.
It is important to recognize that only diagnostic testing
removes residual risk for aneuploidy detection, and 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 not meaningful concerning 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 healthcare
resources, and the patient’s clinical context, values, beliefs,
and potential anxiety created by the identification and discussion of a soft marker.7,16,17 Although any fetal anatomic
survey could be viewed as a screening test for aneuploidy,
identification of a major structural anomaly and discussion
of potential etiologies is standard of care given the likelihood
of identifying a chromosomal abnormality. Identification of
an isolated soft marker, in contrast, does not have a similar
magnitude of association with chromosomal anomalies,
and discussion of the risk of aneuploidy, albeit low, may
potentially conflict with a patient’s desires and values. In
addition, such counseling can generate anxiety, which may
be why the patient declined screening when previously
offered.17 Given the low likelihood of aneuploidy in the
setting of an isolated soft marker, some providers or practices may decide that for pregnant people who have previously declined aneuploidy screening after counseling,
identification of an isolated soft marker will be treated as a
normal variant and neither acknowledged nor discussed,
except for those associated with a need for further imaging
follow-up (eg, UTD, echogenic bowel).
In contrast, other providers or practices may choose to
discuss such findings with all patients and use it as an opportunity to again offer evaluation for aneuploidy or may
individualize counseling based on a patient’s age-related
risk for aneuploidy. 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
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protocols should ensure that patients are informed before
the ultrasound examination of how findings will be handled
to enhance shared decision-making and patient autonomy.
What is the counseling and management
regarding echogenicintracardiac focus?
An EIF is defined as a small (<6 mm) echogenic area in either
cardiac ventricle that is as bright as the surrounding bone
and visualized in at least 2 separate planes.18 EIFs may
appear in either cardiac ventricle, although left-sided EIFs
are more common and are thought to represent microcalcifications of papillary muscles.19,20 The pathogenesis of
this finding is unclear. EIFs do not represent a structural or
functional cardiac abnormality, and they are not associated
with cardiac malformations in the fetus or newborn.21e23
EIFs are identified in 3% to 5% of karyotypically normal
fetuses, and ethnic variation exists.24e27 In the largest
analysis of 7480 ethnically diverse women having amniocentesis, the prevalence of EIF was 8.1% among Middle
Eastern women, 6.9% among Asian American women,
6.7% among African American women, 3.4% among Hispanic women, and 3.3% among White women, with lower
prevalence among Asian Indian and Native American
women.27 Smaller studies have demonstrated a higher
prevalence of EIF among women of Asian descent, with
estimates up to 30%.28,29
Since the first descriptions of EIFs as a soft marker for
trisomy 21, a subsequent large body of literature has
demonstrated varying positive LRs for trisomy 21,
depending on the population studied (low-risk vs high-risk)
and whether the EIF was isolated or in combination with
other soft markers.13,24,26,30e33 In addition, 1 meta-analysis
from 2013 has demonstrated a lack of association between
isolated EIF and trisomy 21, with a positive LR of 0.95.34
Overall, isolated EIFs have a positive LR ranging between
1.4 and 1.8, with a lower confidence interval extending to or
lower than 1, suggesting a minimal risk.32,35
For pregnant people with no previous aneuploidy screening and
an isolated EIF, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive
aneuploidy screening with cfDNA or quad screen if cfDNA is unavailable or cost-prohibitive (GRADE 1B). Although any patient
may request diagnostic testing for any indication, we do not
recommend diagnostic testing solely for this indication. For
pregnant people with negative serum or cfDNA screening results
and an isolated EIF, we recommend no further evaluation, as this
finding is a normal variant of no clinical importance with no
indication for fetal echocardiography, follow-up ultrasound
imaging, or postnatal evaluation (GRADE 1B).
What is the counseling and management
regarding echogenic bowel?
Echogenic bowel is diagnosed when the fetal bowel displays echogenicity equal to or greater than that of the surrounding fetal bone, typically the iliac wing. Transducer
frequency and acoustic gain settings can influence the
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diagnosis because higher frequency transducers and higher
gain settings tend to exaggerate the finding. Therefore, a
lower frequency transducer (5 MHz) with harmonic imaging turned off and set at a lower gain should be used to
confirm the diagnosis.36
Echogenic bowel is observed in up to 1.8% of secondtrimester ultrasound examinations.37e39 Echogenic bowel is
often isolated, but an increased incidence of structural
anomalies, particularly renal and cardiac anomalies, has
been demonstrated in fetuses with echogenic bowel.40
Although isolated echogenic bowel can be a transient or
idiopathic finding in approximately 0.5% of all fetuses, it
also can be associated with a wide range of pathologic
conditions, such as aneuploidy, cystic fibrosis, congenital
viral infection, primary gastrointestinal pathology, intraamniotic bleeding, and fetal growth restriction (FGR). The
estimated incidence of each possible etiology varies
because of small sample size studies and the subjectivity in
the diagnosis.
In fetuses with isolated idiopathic echogenic bowel, the
primary mechanism is thought to be the accumulation of
meconium. Previous studies have demonstrated the idiopathic development of echogenic bowel following invasive
procedures, such as intrauterine fetal transfusions, secondary to fetal swallowing of blood from the amniotic cavity.41 It has been demonstrated that this finding may even
persist for 2 to 4 weeks following intrauterine transfusion.42
Another study has documented subsequent identification of
an echogenic bowel after amniocentesis (performed for the
indication of advanced maternal age), with a strong association between echogenic bowel and blood-tinged or dark
fluid at the time of amniocentesis.43
The estimated incidence of aneuploidy in fetuses with
isolated echogenic bowel ranges from 3% to 5%, with trisomy 21 being the most commonly diagnosed.40,44e49
Other karyotypic abnormalities, such as trisomy 18, trisomy
13, monosomy X, and chromosomal mosaicism, also have
been reported.46,48 Echogenic bowel is an isolated finding in
4% to 25% of fetuses with aneuploidy.40,50 Hypoperistalsis
due to mechanical or functional bowel obstruction with
subsequent dehydration of meconium is the proposed
mechanism causing this finding in fetuses with abnormal
karyotype. The positive LR for trisomy 21 for a fetus with
isolated echogenic bowel depends on the population
studied. Most positive LRs for trisomy 21 range between 6
and 8, suggesting a moderately increased risk, although 1
meta-analysis noted the positive LR for isolated echogenic
bowel to be much lower at 1.65.32e34,51
For pregnant people with no previous aneuploidy screening and
isolated fetal echogenic bowel, we recommend counseling to
estimate the probability of trisomy 21 and a discussion of options
for noninvasive aneuploidy screening with cfDNA or quad screen if
cfDNA is unavailable or cost-prohibitive (GRADE 1B). Although
any patient may request diagnostic testing for any indication, we do not recommend diagnostic testing solely for this
indication. For pregnant people with negative serum or cfDNA
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screening results and isolated fetal echogenic bowel, we recommend no further aneuploidy evaluation (GRADE 1B).
Cystic fibrosis is associated with echogenic bowel, as
abnormal pancreatic enzyme secretion leads to thickened
meconium, and subsequent meconium ileus is observed in
some newborns with cystic fibrosis. The risk for cystic
fibrosis ranges from 0% to 13% in the presence of isolated
echogenic bowel.40,46,48,52 The finding of dilated loops of
bowel in addition to echogenic bowel may increase this risk
to as high as 17%.53 Parental cystic fibrosis carrier status
should be determined if not previously assessed in the
current or a previous pregnancy. If both parents are carriers,
genetic counseling should be undertaken to discuss the
risks and benefits of invasive testing for fetal genotyping.
Racial and ethnic limitations of current cystic fibrosis
screening panels should be considered when interpreting
test results.
In addition, congenital infection has been associated with
isolated echogenic bowel. Different mechanisms underlie
the findings of echogenicity: (1) direct damage to the fetal
intestinal wall with subsequent paralytic ileus, (2) intestinal
perforation resulting in meconium peritonitis and focal
calcification at the perforation sites, or (3) ascites secondary
to hydrops leading to echogenicity on ultrasound. Cytomegalovirus (CMV) is the most commonly observed infection, but toxoplasmosis, rubella, herpes, varicella, and
parvovirus have been reported.36,39,40 Although most
studies report a 2% to 4% incidence of congenital infection
in fetuses with echogenic bowel, rates up to 10% have been
reported.39,54 In a series of 650 cases with maternal primary
CMV infection, 7 fetuses with CMV infection had isolated
echogenic bowel as the sole ultrasound finding.55
Although symptomatic maternal infection is uncommon, a
history should be taken to evaluate for possible timing of
symptoms of CMV. CMV immunoglobulin G (IgG) and IgM
titers should be drawn regardless, with IgG avidity testing as
applicable. If results are suggestive of primary CMV infection (IgM positive and IgG positive with low avidity or IgG
seroconversion), amniocentesis should be considered as a
confirmatory test. Alternatively, if primary CMV infection is
strongly suspected, amniocentesis should be recommended as the initial test to evaluate for this etiology.
Amniocentesis with polymerase chain reaction for CMV
DNA is the best diagnostic test for congenital CMV infection
and is most sensitive when performed after 21 weeks of
gestation and >6 weeks from maternal infection. Negative
serologic results for both IgM and IgG rule out a congenital
CMV infection. Other titer results require further evaluation,
and additional recommendations for evaluation and management of antenatal CMV infection are found in SMFM
Consult #39, Diagnosis and antenatal management of
congenital cytomegalovirus infection.56 Without a history of
exposure or other clinical risk factors, the chance of positive
results for other congenital infections, such as varicella,
herpes, parvovirus, or toxoplasmosis, is very low.57 Therefore, routine testing for these other infections may not be
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useful; however, the utility of testing should be determined
on the basis of the clinical scenario, differential diagnosis,
and potential exposures. For fetuses with isolated echogenic
bowel, we recommend evaluation for cystic fibrosis and fetal CMV
infection (GRADE 1C).
Primary gastrointestinal pathology, such as bowel
obstruction, atresia, and perforation, also may cause an
echogenic appearance of the fetal bowel. In cases of
obstruction and atresia, decreased meconium fluid content
is the proposed cause for the echogenicity. The presence of
meconium outside the intestinal lumen likely is responsible
for the echogenic appearance in cases of bowel perforation.
Finally, isolated echogenic bowel is associated with FGR,
with an odds ratio (OR) of 2.37,40,48 The pathophysiology of
this finding is presumably due to areas of ischemia resulting
from the redistribution of blood flow away from the gut.
Because of this association, we recommend a third-trimester
ultrasound examination for reassessment and evaluation of fetal
growth for all fetuses with isolated echogenic bowel (GRADE 1C).
Although isolated echogenic bowel is associated with an
increased risk of stillbirth, often in the second trimester of
pregnancy, most fetuses with an isolated echogenic bowel
have normal outcomes.37,44,52 The utility of antenatal fetal
testing in this scenario is of unproven benefit. Partial or
complete resolution of isolated echogenic bowel is reassuring, and normal fetal outcomes are likely.58 Normal fetal
outcomes have been demonstrated in fetuses with persistent echogenic bowel as well; thus, persistent echogenicity
should not be viewed as a marker for adverse outcomes.40,59 At the time of delivery, pediatric providers
should be informed of the antenatal finding of echogenic
bowel and a prenatal workup performed so that appropriate
neonatal evaluation may be pursued.
What is the counseling and management
regarding choroid plexus cyst?
A CPC is a small, fluid-filled structure within the choroid of
the lateral ventricles of the fetal brain. On ultrasound, CPCs
appear as echolucent cysts within the echogenic choroid.
CPCs may be single or multiple, unilateral or bilateral, and
most often are <1 cm in diameter. CPCs are identified in
approximately 1% to 2% of fetuses in the second trimester
of pregnancy and are commonly isolated findings in fetuses
with euploidy.60,61
CPCs are associated with trisomy 18, as they are present
in 30% to 50% of fetuses with this disorder.62 When a fetus
is affected by trisomy 18, multiple structural anomalies are
almost always evident, including structural heart defects,
clenched hands, talipes deformity of the feet, FGR, and
polyhydramnios. When a structural anomaly is present in
addition to CPCs, the positive LR is 66.62
In the absence of other ultrasonographic abnormalities,
the likelihood of trisomy 18 with isolated CPCs is much
lower. Early studies suggested that isolated CPCs conferred
a 1 in 200 to 1 in 400 risk of trisomy 18.63,64 More recent
studies among women with isolated CPCs suggest a range
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of positive LRs for trisomy 18, from 0.9 to 5.6, with most
studies suggesting low risk.62,65e67 Based on the literature,
the best estimate for the LR is <2, suggesting a minimal risk.
The presence of a CPC does not alter the risk of trisomy
21.68 For pregnant people with no previous aneuploidy screening
and isolated CPCs, we recommend counseling to estimate the
probability of trisomy 18 and a discussion of options for noninvasive aneuploidy screening with cfDNA or quad screen if cfDNA is
unavailable or cost-prohibitive (GRADE 1C). Although any patient may request diagnostic testing for any indication, we
do not recommend diagnostic testing solely for this indication. For pregnant people with negative serum or cfDNA
screening results and isolated CPCs, we recommend no further
aneuploidy evaluation, as this finding is a normal variant of no
clinical importance with no indication for follow-up ultrasound
imaging or postnatal evaluation (GRADE 1C). Ultrasound characteristics of CPCs (size, complexity, laterality, and persistence) should not be used to modify risk further because
these factors do not impact the likelihood of trisomy 18.63
A CPC is not considered a structural or functional brain
abnormality, and nearly all CPCs resolve by 28 weeks.69
Patients may be counseled that neurodevelopmental outcomes in children with euploidy born after a prenatal diagnosis of CPCs have not shown differences in neurocognitive
ability, motor function, or behavior.70e73
What is the counseling and management
regarding a single umbilical artery?
The normal umbilical cord contains 2 arteries and 1 vein. An
SUA results from atrophy or agenesis of 1 of the arteries. An
SUA can be detected on a cross section of the umbilical
cord during a routine second-trimester ultrasound examination. In addition, an SUA can be detected using color flow
Doppler to examine the umbilical arteries in the pelvis, even
at early gestational ages.
The incidence of SUA is 0.25% to 1% of all singleton
pregnancies and up to 4.6% of twin gestations.74e76 An
isolated SUA with no other structural or chromosomal abnormality should be distinguished from an SUA that is present with other abnormalities. Co-occurring structural
abnormalities most commonly involve the cardiovascular
and renal systems.75 With an SUA and one or multiple
structural abnormalities, the frequency of associated aneuploidy ranges from 4% to 50%.77 A comprehensive
assessment of cardiac anatomy (76811 ultrasound) should
be performed, and if required cardiac views are adequately
visualized and normal, fetal echocardiography is not routinely
warranted.78,79 For patients with an isolated SUA, there appears to be no increased risk of aneuploidy.77,80 For fetuses
with an isolated SUA, we recommend no additional evaluation for
aneuploidy, regardless of whether previous aneuploidy screening
results were low risk or screening was declined (GRADE 1C).
Isolated SUA has been associated in some studies with an
increased risk of stillbirth and FGR, although other studies
suggest that an isolated SUA does not place the fetus at
increased risk of FGR.81e85 In a population-based
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case-control study, SUA was associated with an increased
OR of stillbirth compared with live birth (OR, 4.80; 95%
confidence interval [CI], 2.67e8.62).86 In a cohort of fetuses
with isolated SUA, the observed incidence of FGR was not
higher than that expected.85 However, another study with a
large control group of fetuses with a 3-vessel cord did
demonstrate an increased risk of FGR, polyhydramnios,
oligohydramnios, placental abruption, cord prolapse, and
perinatal mortality after controlling for other confounders.82
Given the conflicting evidence and increased risks of stillbirth, we recommend a third-trimester ultrasound examination to
evaluate growth and consideration of weekly antenatal fetal
surveillance beginning at 36 0/7 weeks of gestation for fetuses
with an isolated SUA (GRADE 1C).87 At the time of delivery, the
pediatric provider should be notified of the prenatal findings.
Postnatal examination of infants with a prenatal diagnosis of
isolated SUA revealed structural anomalies in up to 7% of
fetuses in 1 study.88
What is the counseling and management
regarding urinary tract dilation?
Several terms have been used to describe UTD,
including pyelectasis, pelviectasis, and hydronephrosis.
UTD occurs in 1% to 2% of pregnancies and is most
commonly a transient finding that is a normal variant.89
UTD may indicate renal or urinary tract pathology and
may also be a marker of trisomy 21. The association
between trisomy 21 and UTD has been well described in
several series, and the finding of UTD confers a positive
LR of 1.5, suggesting a minimal risk.32 For pregnant people
with no previous aneuploidy screening and isolated UTD, we
recommend counseling to estimate the probability of trisomy
21 and a discussion of options for noninvasive aneuploidy
screening with cfDNA or quad screen if cfDNA is unavailable
or cost-prohibitive (GRADE 1B). Although any patient may
request diagnostic testing for any indication, we do not
recommend diagnostic testing solely for this indication.
For pregnant people with negative serum or cfDNA screening
results and isolated UTD, we recommend no further aneuploidy evaluation (GRADE 1B).
In 2014, a consensus statement defined norms for antenatal UTD based on anterior-posterior renal pelvis diameter,
with <4 mm being normal between 16 and 27 weeks of
gestation and <7 mm being normal between 28 weeks of
gestation and delivery.89 To fully assess and classify UTD,
additional ultrasound features to be evaluated include the
presence of calyceal dilation, parenchymal thickness and
appearance, ureteral dilation, bladder abnormalities, and
amniotic fluid volume. The complete evaluation of the urinary tract results in the classification of A1 (low risk) vs A2-3
(increased risk) UTD, which guides antenatal management
and postnatal follow-up (Table 2). UTD between 4 and 7 mm
in the second trimester of pregnancy resolves in approximately 80% of cases.89 Consistent with the 2014
consensus statement, for fetuses with isolated UTD A1, we
recommend an ultrasound examination at ‡32 weeks of gestation
to determine if postnatal pediatric urology or nephrology followup is needed. For fetuses with UTD A2-3, we recommend an
individualized follow-up ultrasound assessment with planned
postnatal follow-up (GRADE 1C).
In a minority of cases, UTD has a pathologic cause.
Common pathologic causes include vesicoureteral reflux
(the most common etiology), ureteropelvic junction
obstruction, ureterovesical junction obstruction, multicystic
dysplastic kidneys, and posterior urethral valves. Although
some conditions can be diagnosed antenatally, in most
TABLE 2
Urinary tract dilation (UTD): Antenatal classification of findings
UTD A1
UTD A2-3
AP RPD, 16e27 wk of gestation
4 to <7 mm
7 mm
AP RPD, 28 wk of gestation
7 to <10 mm
10 mm
Calyceal dilation
None or central
None, central, or peripheral
Parenchymal thickness
Normal
Normal or abnormal
Parenchymal appearance
Normal
Normal or abnormal
Ultrasound findings
Ureters
Normal
Normal or abnormal
Bladder
Normal
Normal or abnormal
Unexplained oligohydramnios
Absent
Absent or present
Prenatal follow-up
Third-trimester ultrasound
examination at 32 wks of gestation
Individualized follow-up
ultrasound examination
Adapted from Nguyen et al.89
AP RPD, anterior-posterior renal pelvis diameter; UTD, urinary tract dilation.
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Summary of recommendations
Number
Recommendations
GRADE
1
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.
1B
Strong recommendation,
moderate-quality evidence
2
For pregnant people with no previous aneuploidy screening and isolated echogenic intracardiac
focus, echogenic bowel, UTD, or shortened humerus, femur, or both, we recommend counseling to
estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy
screening with cfDNA, or quad screen if cfDNA is unavailable or cost-prohibitive.
1B
Strong recommendation,
moderate-quality evidence
3
For pregnant people with no previous aneuploidy screening and isolated thickened nuchal fold or
isolated absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of
trisomy 21 and a discussion of options for noninvasive aneuploidy screening via cfDNA or quad
screen if cfDNA is unavailable or cost-prohibitive or diagnostic testing via amniocentesis,
depending on clinical circumstances and patient preference.
1B
Strong recommendation,
moderate-quality evidence
4
For pregnant people with no previous aneuploidy screening and isolated CPCs, we recommend
counseling to estimate the probability of trisomy 18 and discussion of options for noninvasive
aneuploidy screening with cfDNA or quad screen if cfDNA is unavailable or cost-prohibitive.
1C
Strong recommendation,
low-quality evidence
5
For pregnant people with negative serum or cfDNA screening results and an isolated echogenic
intracardiac focus, we recommend no further evaluation, as this finding is a normal variant of no
clinical importance with no indication for fetal echocardiography, follow-up ultrasound imaging, or
postnatal evaluation.
1B
Strong recommendation,
moderate-quality evidence
6
For pregnant people with negative serum or cfDNA screening results and isolated fetal echogenic
bowel, UTD, or shortened humerus, femur, or both, we recommend no further aneuploidy
evaluation.
1B
Strong recommendation,
moderate-quality evidence
7
For pregnant people with negative serum screening results and isolated thickened nuchal fold or
absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy
21 and a discussion of options for no further aneuploidy evaluation, noninvasive aneuploidy
screening via cfDNA, or diagnostic testing via amniocentesis, depending on clinical circumstances
and patient preference.
1B
Strong recommendation,
moderate-quality evidence
8
For pregnant people with negative cfDNA screening results and isolated thickened nuchal fold or
absent or hypoplastic nasal bone, we recommend no further aneuploidy evaluation.
1B
Strong recommendation,
moderate-quality evidence
9
For pregnant people with negative serum or cfDNA screening results and isolated CPCs, we
recommend no further aneuploidy evaluation, as this finding is a normal variant of no clinical
importance with no indication for follow-up ultrasound imaging or postnatal evaluation.
1C
Strong recommendation, lowquality evidence
10
For fetuses with isolated echogenic bowel, we recommend evaluation for cystic fibrosis and fetal
CMV infection and a third-trimester ultrasound examination for reassessment and evaluation of
fetal growth.
1C
Strong recommendation, lowquality evidence
11
For fetuses with an isolated SUA, we recommend no additional evaluation for aneuploidy,
regardless of whether previous results of aneuploidy screening were low risk or testing was
declined. We recommend a third-trimester ultrasound examination to evaluate growth and
consideration of weekly antenatal fetal surveillance beginning at 36 0/7 wk of gestation.
1C
Strong recommendation, lowquality evidence
12
For fetuses with isolated UTD A1, we recommend an ultrasound examination at ‡32 wk of gestation
to determine if postnatal pediatric urology or nephrology follow-up is needed. For fetuses with UTD
A2-3, we recommend an individualized follow-up ultrasound assessment with planned postnatal
follow-up.
1C
Strong recommendation, lowquality evidence
13
For fetuses with isolated shortened humerus, femur, or both, we recommend a third-trimester
ultrasound examination for reassessment and evaluation of growth.
1C
Strong recommendation, lowquality evidence
cfDNA, cell-free DNA; CMV, cytomegalovirus; CPC, choroid plexus cyst; SUA, single umbilical artery; UTD, urinary tract dilation.
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Society for Maternal-Fetal Medicine grading system: Grading of Recommendations Assessment,
Development, and Evaluation recommendations108,a
GRADE of
recommendation
Clarity of risk and benefit
Quality of supporting evidence
Implications
1A. Strong
recommendation,
high-quality evidence
Benefits clearly outweigh risks and
burdens, or vice versa.
Consistent evidence from wellperformed, RCTs, or overwhelming
evidence of some other form. Further
research is unlikely to change
confidence in the estimate of benefit
and risk.
Strong recommendation that can
apply to most patients in most
circumstances without
reservation. Clinicians should
follow a strong recommendation
unless a clear and compelling
rationale for an alternative
approach is present.
1B. Strong
recommendation,
moderate-quality
evidence
Benefits clearly outweigh risks and
burdens, or vice versa.
Evidence from RCTs with important
limitations (inconsistent results,
methodologic flaws, indirect or
imprecise) or very strong evidence of
some other research design. Further
research (if performed) is likely to have
an impact on confidence in the
estimate of benefit and risk and may
change the estimate.
Strong recommendation that
applies to most patients.
Clinicians should follow a strong
recommendation unless a clear
and compelling rationale for an
alternative approach is present.
1C. Strong
recommendation,
low-quality evidence
Benefits seem to outweigh risks and
burdens, or vice versa.
Evidence from observational studies,
unsystematic clinical experience, or
RCTs with serious flaws. Any estimate
of effect is uncertain.
Strong recommendation that
applies to most patients. However,
some of the evidence base
supporting the recommendation is
of low quality.
2A. Weak
recommendation,
high-quality evidence
Benefits are closely balanced with
risks and burdens.
Consistent evidence from wellperformed RCTs or overwhelming
evidence of some other form. Further
research is unlikely to change
confidence in the estimate of benefit
and risk.
Weak recommendation; best
action may differ depending on
circumstances or patients or
societal values.
2B. Weak
recommendation,
moderate-quality
evidence
Benefits are closely balanced with
risks and burdens; there are some
uncertainties in the estimates of
benefits, risks, and burdens.
Evidence from RCTs with important
limitations (inconsistent results,
methodologic flaws, indirect or
imprecise) or very strong evidence of
some other research design. Further
research (if performed) is likely to have
an effect on confidence in the
estimate of benefit and risk and may
change the estimate.
Weak recommendation;
alternative approaches are likely
to be better for some patients
under some circumstances.
2C. Weak
recommendation,
low-quality evidence
There are uncertainties in the
estimates of benefits, risks, and
burdens; benefits may be closely
balanced with risks and burdens.
Evidence from observational studies,
unsystematic clinical experience, or
RCTs with serious flaws. Any estimate
of effect is uncertain.
Very weak recommendation, other
alternatives may be equally
reasonable.
Best practice
Recommendation in which either (1)
there is an enormous amount of
indirect evidence that clearly justifies
strong recommendation (direct
evidence would be challenging, and
inefficient use of time and resources,
to bring together and carefully
summarize) or (2) recommendation to
the contrary would be unethical.
GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RCT, randomized controlled trial.
a
Adapted Guyatt et al.109
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cases, the diagnosis is made postnatally.89 At the time of
delivery, the diagnosis of UTD A1 or A2-3 should be
communicated with the pediatric provider; however,
resolved UTD A1 demonstrated at the third-trimester ultrasound examination requires no postnatal follow-up.89
What is the counseling and management
regarding shortened humerus, femur, or
both?
A shortened humerus and shortened femur have been variably
defined throughout the literature. For aneuploidy screening,
a shortened humerus is identified when the ratio of the
observed to expected humeral length (based on biparietal
diameter) is <0.90.90,91 Similarly, a shortened femur is identified when the ratio of the observed femoral length to expected
femoral length (based on biparietal diameter) is <0.92.2,91
With these thresholds, the singular presence of either of
these markers has been associated with trisomy 21, with
higher specificity for shortened humeri. For shortened femurs, the positive LR from meta-analyses ranges from 1.5 to
2.7, with the CI of the lower estimate crossing 1, suggesting
a minimally elevated risk.32,33 For shortened humeri, the
positive LR from meta-analyses ranges from 5.1 to 7.5,
suggesting a moderate risk.32,33 Racial and ethnic variation
in the normal distribution for femoral length in the midtrimester has been described in some studies, with femoral
bones being shorter among Asian participants and longer
among Black participants.92,93 Similar variation has not
been described for midtrimester humeral lengths, and raceand ethnicity-specific definitions of foreshortened humerus,
femur, or both do not improve diagnostic test characteristics for trisomy 21 detection.94,95 Parental race and ethnicity
can lead to constitutionally short bones and should be
considered in the differential diagnosis.
For pregnant people with no previous aneuploidy screening
and isolated shortened humerus, femur, or both, we recommend counseling to estimate the probability of trisomy 21
and a discussion of options for noninvasive aneuploidy
screening with cfDNA or quad screen if cfDNA is unavailable
or cost-prohibitive (GRADE 1B). Although any patient may
request diagnostic testing for any indication, we do not
recommend diagnostic testing solely for this indication.
For pregnant people with negative cfDNA or serum screening
results and isolated shortened humerus, femur, or both, we
recommend no further aneuploidy evaluation (GRADE 1B).
The finding of shortened humerus, femur, or both is
associated with skeletal dysplasia. A thorough evaluation
and measurement of all appendicular bones should be
performed and compared with nomograms for bone length
by gestational age. In general, many fetuses with skeletal
dysplasias fall below the third percentile for bone length
measurements in the second trimester of pregnancy, except
for achondroplasia, which may not manifest until the third
trimester of pregnancy.96
Finally, isolated shortened humerus, femur, or both are
associated with FGR.97,98 For fetuses with isolated shortened
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humerus, femur, or both, we recommend a third-trimester ultrasound examination for reassessment and evaluation of growth
(GRADE 1C).
What is the counseling and management
regarding thickened nuchal fold?
The nuchal fold is imaged in the transverse plane of the fetal
head, angled caudally to capture the cerebellum and occipital bone, and calipers are placed between the outer edge
of the skin and outer edge of the occipital bone. A thickened
nuchal fold is defined as 6 mm between 15 and 20 weeks
of gestation.99 Thickened nuchal fold was one of the first
identified ultrasound markers of trisomy 21 and is one of the
most specific markers to date.99,100 After the initial report,
several prospective series of consecutive amniocenteses
confirmed the association between an isolated thickened
nuchal fold and trisomy 21, with rare false-positive
cases.1,2,100 The positive LR ranges between 11 and 23,
suggesting a substantial risk.32e34 However, when identified as an isolated marker, the positive LR is estimated to be
3.8.34
For pregnant people with no previous aneuploidy screening and
isolated thickened nuchal fold, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for
noninvasive aneuploidy screening via cfDNA or quad screen if
cfDNA is unavailable or cost-prohibitive or diagnostic testing via
amniocentesis, depending on clinical circumstances and patient
preference (GRADE 1B). For pregnant people with negative serum
screening results and isolated thickened nuchal fold, we recommend counseling to estimate the probability of trisomy 21 and a
discussion of options for no further aneuploidy evaluation,
noninvasive aneuploidy screening via cfDNA, or diagnostic testing
via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B). Given the high LR described in
the literature for this marker and the variation in aneuploidy
DRs across serum screening methods, the residual risk of
trisomy 21 in a particular patient may increase above a
threshold at which further evaluation would typically be
considered. Conceptualizing this residual risk may help the
patient decide whether to pursue no additional evaluation,
noninvasive screening, or diagnostic testing. For pregnant
people with negative cfDNA screening results and isolated
thickened nuchal fold, we recommend no further aneuploidy
evaluation (GRADE 1B).
Regardless of the aneuploidy evaluation pursued, serial
ultrasound examinations of the evolution of the thickened
nuchal fold are not indicated. Conflicting evidence exists
regarding the association between a thickened nuchal fold
and congenital heart disease; however, if cardiac anatomy
has been adequately visualized and appears normal, no
further imaging is necessary.12
What is the counseling and management of
absent or hypoplastic nasal bone?
The nasal bone is imaged perpendicular to the longitudinal
axis of the nose, in the midsagittal plane of the fetal face.99
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A hypoplastic nasal bone in the second trimester of pregnancy is defined as a ratio against the biparietal diameter
(biparietal diameter-to-nasal bone 10 or 11), by length
(2.5 mm), by gestational age-based percentiles (<2.5th
percentile), or by multiples of the median (<0.75 or 0.7
MoM), the latter of which has been demonstrated to have
better test characteristics for the identification of trisomy
21.101,102
Absent or hypoplastic nasal bone occurs in 0.1% to 1.2%
of euploid pregnancies.103,104 Ethnic variation is known to
occur in some populations. Absent or hypoplastic nasal
bones in the second trimester of pregnancy have been seen
in 9% of the Afro-Caribbean population; however, another
study has demonstrated no difference in normative values
between White and Asian populations.103,105
The association between absent or hypoplastic nasal
bone in the second trimester of pregnancy and trisomy 21 is
well described. In many cases, these findings occur with
other structural anomalies or soft markers; there are limited
data on the increased risk of trisomy 21 with an isolated
absent or hypoplastic nasal bone.103,106,107 In 1 metaanalysis, the positive LR of absent or hypoplastic nasal bone
was 23, suggesting a high risk, although there was substantial heterogeneity in the studies included in this metaanalysis.34 When considered as an isolated marker, the
positive LR is 6.6.34 The wide range of positive LRs reflects
not only whether the marker was isolated but also differences based on the ethnicities of the populations included in
these studies, and there are limited data to provide
ethnicity-specific LRs.
For pregnant people with no previous aneuploidy screening
and isolated absent or hypoplastic nasal bone, we recommend
counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening through
cfDNA or quad screen if cfDNA is unavailable or cost-prohibitive
or diagnostic testing via amniocentesis, depending on clinical
circumstances and patient preference (GRADE 1B). For pregnant
people with negative serum screening results and isolated absent or hypoplastic nasal bone, we recommend counseling to
estimate the probability of trisomy 21 and a discussion of options
for no further aneuploidy evaluation, noninvasive aneuploidy
screening via cfDNA, or diagnostic testing via amniocentesis,
depending on clinical circumstances and patient preference
(GRADE 1B). Given the high LR described in the literature for
this marker and the variation in aneuploidy DRs across
serum screening methods, the residual risk of trisomy 21 in
a particular patient may increase above a threshold at
which further evaluation would typically be considered.
Conceptualizing this residual risk may help the patient
decide whether to pursue no additional evaluation,
noninvasive evaluation, or diagnostic testing. For pregnant
people with negative cfDNA screening results and isolated absent or hypoplastic nasal bone, we recommend no further
aneuploidy evaluation (GRADE 1B). In the presence of a low
risk for aneuploidy, this finding is of little clinical importance and is most likely a normal variant. We do not
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recommend any additional antenatal ultrasound surveillance for this finding alone. Absent nasal bone can be
associated with other genetic syndromes; therefore,
careful evaluation of anatomy in the setting of this finding is
warranted.
Conclusion
With advances in prenatal screening for fetal aneuploidy, the
relative impact of soft ultrasound markers in assessing the
risk for aneuploidy has decreased since their initial introduction to routine prenatal care. When an isolated soft
marker is identified after negative screening results, patients
may be reassured that the risks of fetal aneuploidy remain
low. However, the identification of soft markers remains
important to evaluate for associated conditions that are
n
unrelated to fetal aneuploidy.
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