INTRODUCTION — A small, thin hypoechoic space in the posterior fetal neck is a common finding in normal first-trimester fetuses. In some fetuses, this space is enlarged due to a cystic hygroma or mesenchymal edema (called enlarged or increased nuchal translucency [NT]) (image 1). These fetuses are at increased risk for structural abnormalities and aneuploidy, particularly Down syndrome (trisomy 21).
The diagnosis, clinical significance, and management of pregnancies complicated by a cystic hygroma or enlarged NT will be reviewed here. The use of NT measurement in prenatal screening for Down syndrome as part of the first trimester combined test and the full integrated test is reviewed separately (see "Down syndrome: Overview of prenatal screening", section on 'Choice of screening test in singleton pregnancies'). Other ultrasound markers that may be associated with aneuploidy are also reviewed separately. (See "Sonographic findings associated with fetal aneuploidy".)
ENLARGED NUCHAL TRANSLUCENCY
Anatomy — The term "nuchal translucency" refers to the hypoechoic region located between the skin and soft tissues behind the cervical spine (image 2A). This hypoechoic space is presumed to represent mesenchymal edema and is often associated with distended jugular lymphatics [1,2].
A small but measurable amount of nuchal fluid can be identified in virtually all fetuses between the 10th and 14th week of gestation and is considered a normal finding if below a defined threshold (see 'Prenatal diagnosis' below). Above this threshold, the fetus is considered to have enlarged NT.
Pathogenesis — The pathogenesis of nuchal edema is unknown, but is probably multifactorial and differs depending on the underlying fetal disorder [3,4]. For example:
●In trisomy 21 the collagen content of the dermis is abnormal; its hydrophilic properties may lead to the accumulation of subcutaneous fluid.
●In Turner syndrome, lymphatic dysplasia may lead to increased nuchal fluid, or narrowing of the aortic isthmus and widening of the ascending aorta may lead to overperfusion of the head and neck, thus contributing to the development of subcutaneous edema.
●In fetuses with abnormal nuchal lymphatic development, distension of the jugular lymphatic sacs, accumulation of fluid in the nuchal region, and retrograde increases in venous pressure may occur.
●In fetuses with congenital heart disease, pathogenic variants in genes encoding for endothelium and involved in both cardiac and lymphatic development may contribute to increases in nuchal fluid [5-7].
●For patients who choose to have the first-trimester combined test or an integrated screening test for Down syndrome, NT is measured as a routine part of the test. (See "First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18".)
●For patients who choose to have cell-free DNA (cfDNA) as their primary screening test for fetal aneuploidy, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend not performing an ultrasound examination at 11 to 14 weeks of gestation to specifically measure the NT for aneuploidy screening . The residual risk of a significant chromosomal abnormality in these patients is low. However, an ultrasound examination at 11 to 14 weeks may still be warranted for the early detection of major malformations, multiple gestation, or fetal demise . While some anatomic abnormalities can be detected on a first-trimester ultrasound, cardiac anomalies that are most commonly associated with enlarged NT are optimally detected at 18 to 22 weeks.
However, some of these patients may be subsequently found to have an enlarged NT of ≥3.0 to 3.5 mm (guidelines vary as to the specific NT threshold) as an incidental finding on an ultrasound performed for another indication. Such patients should be referred for genetic counseling to discuss prognostic implications and the consideration of further genetic testing and for fetal echocardiography to screen for congenital heart disease. (See 'Postdiagnostic evaluation' below.)
●For patients who cannot decide whether to have a screening test or a diagnostic test as their initial test for Down syndrome, assessment of NT can help some individuals, especially those at higher risk for aneuploidy, make the decision. If NT is normal, they may be comfortable choosing to have a noninvasive screening test whereas, if NT is enlarged, they may be more comfortable choosing to have an invasive diagnostic procedure for fetal microarray, since there is an increased risk of genomic abnormalities in this setting.
In high-risk patients (defined as enlarged NT with or without biochemical markers of Down syndrome, structural anomalies, advanced maternal age/anxiety, or family history) who choose to undergo cfDNA screening, the residual risk of a significant chromosomal abnormality is 2.5 percent in those who have a normal cfDNA test result . These abnormalities include microdeletions/microduplications and RASopathies (eg, Noonan syndrome). The residual risk can be reduced to 1 percent if cfDNA screening is performed when NT is <3 mm and chorionic villus sampling (CVS) is performed when NT is ≥3 mm, but this approach also increases the frequency of invasive testing from 2 to 22 percent.
An enlarged NT may be the only sonographic abnormality in 20 percent of fetuses with RASopathies and is frequently large [10,11]. In one study, the optimal NT threshold for RASopathy screening was 7.9 mm, resulting in a detection rate of 2.9 percent . Based on a cohort of 424 fetuses with a RASopathy, diagnostic testing has been suggested for an isolated enlarged NT ≥5 mm .
Prenatal diagnosis — Prenatal diagnosis of enlarged NT is based upon ultrasound measurement of the nuchal fluid space when the crown-rump length is 36 to 84 mm, which corresponds to approximately 10 to 14 weeks of gestation . The optimal time to assess the NT is at 11 weeks of gestation.
The most commonly used thresholds for diagnosis of enlarged NT are the 95th and 99th percentiles for gestational age as measured by the crown rump length (NT normally increases with gestational age). We use the 99th percentile.
Calculators are available online that enable clinicians to enter the crown-rump length and NT measurement to obtain the NT percentile (one such calculator is available at perinatology.com).
Procedure — The American Institute of Ultrasound in Medicine (AIUM), American College of Radiology, ACOG, SMFM, and Society of Radiologists in Ultrasound Practice Parameter for the Performance of Standard Diagnostic Obstetric Ultrasound Examinations state the following :
●The margins of the NT edges should be clear with the angle of insonation perpendicular to the NT line.
●The fetus should be in the midsagittal plane, with visualization of the tip of the nose, palate, and diencephalon.
●The fetal head, neck, and upper thorax should be magnified to fill the image.
●The fetal neck should be in a neutral position (the head in line with the spine, not flexed, and not hyperextended).
●The amnion should be seen as separate from the NT line. Care must be taken to identify the amnion since it may be separate from the chorion until 16 weeks of gestation and thus may be mistakenly identified as the posterior aspect of the fetal skin (image 2A-B).
●The electronic calipers must be placed on the inner borders of the nuchal line with none of the horizontal crossbar itself protruding into the space. The calipers must be placed perpendicular to the long axis of the fetus.
●The (+) calipers on the ultrasound screen should be used to measure NT. The measurement must be obtained at the widest space of the NT.
●There is a significant learning period for performing accurate NT measurements in the first trimester. In two large multicenter studies of first-trimester Down syndrome screening, accurate NT measurement required stringent training, formalized evaluation of sonographer's competence, and continuing external quality control [14,15]. In the latter trial , adequate NT images could not be obtained in 6 percent of cases.
●Fetal position and maternal body habitus can make accurate measurement difficult .
●NT measurements vary from week to week, and we have observed that abnormal measurements can quickly revert to normal, even if the fetus is abnormal. Therefore, when an abnormal measurement is obtained, we counsel the patient according to that measurement and do not revise counseling if a subsequent measurement is normal.
Clinical significance — Enlarged NT has been associated with increased risks for aneuploidy and structural abnormalities (particularly congenital heart disease), which are, in turn, associated with increased risks for miscarriage, fetal demise, or neonatal death. Enlarged NT may also be associated with developmental and genetic syndromes and, in monochorionic twins, twin-twin transfusion syndrome.
The magnitude of enlarged NT is an important prognostic factor [17-23]. In one study, for example, first-trimester NT 3.5 to 4.4 mm was associated with a normal outcome in 70 percent of fetuses whereas NT 5.5 to 6.4 mm was associated with a normal outcome in only 30 percent of cases .
Aneuploidy — NT is measured primarily as one component of the first-trimester combined screening test for trisomy 21 (Down syndrome). The risk of Down syndrome is calculated from an equation that takes into account NT thickness, maternal biochemical marker levels, and maternal age. (See "First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18".)
Trisomy 21 is the most common aneuploidy associated with enlarged NT [24-27]. However, trisomy 13 (Patau syndrome), trisomy 18 (Edward syndrome), monosomy X (Turner syndrome), and triploidy are also found with increased frequency among fetuses with enlarged NT.
The likelihood of aneuploidy increases with increasing NT above the 95th percentile for gestational age. For example, at 11+0 to 13+6 weeks, the frequency of aneuploidy at an NT between the 95th percentile (approximately 3 mm) and 3.4 mm, 3.5 to 4.4 mm, 5.5 to 6.4 mm, and ≥8.5 mm was 7, 20, 50, and 75 percent, respectively, in one study . In this study, most fetuses with trisomy 21 had an NT less than 4.5 mm, and most fetuses with trisomy 13, trisomy 18, and Turner syndrome had nuchal thickness ≥4.5 mm.
Structural abnormalities — The overall frequency of structural anomalies in euploid fetuses with enlarged NT ranges from 4 to 10 percent [17,28].
Congenital heart disease — Enlarged NT is an early marker of congenital cardiac anomalies: in a large study, 37 percent of fetuses diagnosed with a major cardiac abnormality had NT ≥95th percentile on a routine 11 to 13 weeks of gestation ultrasound examination, whereas only 6 percent of fetuses with a normal heart had enlarged NT on this examination . Cardiac anomalies are the most common malformation associated with enlarged NT, and septal defects are the most common cardiac abnormality.
The overall frequency of congenital heart disease increases with increasing NT [30-32]. Depending on the cutoff used (95th versus 99th percentile), the overall frequency of a critical cardiac anomaly in a euploid fetus with enlarged NT ranges from approximately 2 to 6 percent, which is severalfold higher than the 0.6 percent baseline risk of moderate and severe forms of congenital heart disease in the general obstetric population [32,33]. In a large study, a threshold of ≥99th percentile was more than twice as sensitive as an absolute cutoff of ≥3.5 mm (sensitivity 5.8 versus 2.6 percent) .
Noncardiac anomalies — In a large population-based study of euploid live born infants without critical congenital heart anomalies, those with NT measurements ≥95th percentile (approximately 3 mm), ≥99th percentile, or ≥3.5 mm were at greater risk of having a noncardiac major structural congenital anomaly than infants with NT <90th percentile (relative risk [RR] 1.5, 2.2, and 3.1, respectively) .
The risk of the following anomalies was increased approximately threefold in infants with NT measurements ≥95th percentile compared with infants with NT <95th percentile:
●Agenesis, hypoplasia, and dysplasia of the lung
●Atresia and stenosis of the small intestine
Genetic syndromes — Over 100 developmental and genetic syndromes have been associated with enlarged NT [18,35]. In addition to the common aneuploidies discussed above, Noonan syndrome, multiple pterygium syndrome, Roberts syndrome, Cornelia de Lange syndrome, congenital adrenal hyperplasia, spinal muscular atrophy, DiGeorge syndrome, Smith-Lemli-Opitz syndrome, and a variety of skeletal dysplasias have been diagnosed in children who had enlarged NT in utero [12,36]. Some, but not all, of these syndromes are associated with pathogenic variants or structural abnormalities that can be detected prenatally .
Developmental delay — In children with enlarged NT in utero, normal karyotype, and no structural anomalies or other characteristics associated with genetic syndromes, a systematic review including 17 studies found that the prevalence of developmental delay was 28 in 2458 (1.4 percent), which is not higher than the rate in the general population . The pooled rate of developmental delay did not significantly differ according to the cutoff used to define enlarged NT (95th centile, 3.0 mm, or 99th centile).
These and subsequent data from large studies [38,39] are reassuring for pregnancies with no abnormalities after postdiagnostic evaluation; however, there are several limitations to the available data, including lack of a standard definition of developmental delay, often inadequate methods for ascertainment of cases and developmental assessment, and incomplete identification of syndromes. Additional standardized pediatric evaluations and long-term neurodevelopmental follow-up studies are needed to better define these risks.
Twin-twin transfusion — Enlarged NT or >20 percent discordance between NT measurements in monochorionic twins is predictive of twin-twin transfusion syndrome (TTTS) . In one study, discordance >20 percent was associated with a >30 percent risk of early fetal death or development of severe TTTS compared with a <10 percent risk when discordance is <20 percent . (See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis" and "Twin-twin transfusion syndrome: Management and outcome".)
Natural history — In normal fetuses, enlarged NT commonly resolves spontaneously by the second trimester [18,20,23,42,43]. Persistence is a marker for an underlying abnormality. A large or persistent nuchal fluid accumulation appears to be a poor prognostic factor, even in euploid nonanomalous fetuses .
Postdiagnostic evaluation — After a diagnosis of enlarged NT, the author's postdiagnostic evaluation includes:
●Genetic counseling, including options for fetal genetic testing
●Fetal anatomic survey at the time of NT measurement and at 18 to 22 weeks of gestation
●Fetal echocardiography at 18 to 22 weeks of gestation
●Periodic assessment of fetal well-being
Genetic studies — For patients who have had enlarged NT identified as part of the first-trimester combined test or integrated test for aneuploidy, primarily Down syndrome screening, either CVS or amniocentesis for definitive genetic diagnosis is offered. Offering secondary screening with a cfDNA test of maternal blood is also supported by ACOG and SMFM and should include counseling that addresses the potential benefit of reducing the chances of a false-positive screen but emphasizes that cfDNA is not a diagnostic test. (See "First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18", section on 'Screen-positive first-trimester combined test results'.)
In some cases in which NT is measured before serum analytes have been drawn, it is reasonable to offer diagnostic genetic studies after measurement of NT without performing the full combined test or integrated test. The optimum NT threshold for proceeding directly to an invasive diagnostic test is unclear. Absolute thresholds of 3.0 to 4.0 mm have been suggested, given the relatively high risk of aneuploidy and the availability of genetic testing for some of the associated conditions, such as the RASopathies [17,44-46].
In our practice, we use a threshold ≥3 mm for offering immediate CVS. In a large observational study, 92 percent of patients with NT measurement ≥3 mm will screen positive on the combined test and be offered invasive testing . Offering prompt invasive testing based on NT alone shortens the time between the positive screen and obtaining a definitive diagnosis. Some clinicians use a threshold of ≥3.5 mm, which corresponds with the 99th percentile in populations at high risk of aneuploidy, regardless of crown-rump length . However, among 619 patients with isolated NT 3.0 to 3.4 mm in one study, 29 (4.7 percent) had abnormal microarray analysis consisting of 12 cases of trisomy 21 (one mosaic), 3 cases of trisomy 18 (one mosaic), 2 cases of sex chromosome aneuploidy (47, XXX and 47, XXY), 3 single cases of other abnormalities, and 9 cases of submicroscopic clinically significant copy number variants . The 4.7 percent rate of abnormality was threefold higher than the 0.76 percent rate in a control cohort of fetuses with normal ultrasound findings and NT <3.0 mm (RR 3.3, 95% CI 2.6-4.2).
Microarray — We offer microarray genetic analysis rather than a conventional G-banded karyotype to all patients undergoing invasive genetic studies. In a systematic review of pooled data from 17 studies and 1696 pregnancies, the incremental yield of microarray over conventional karyotyping was 4 percent among fetuses with isolated enlarged NT and 7 percent among fetuses with enlarged NT associated with abnormalities diagnosed by first-trimester ultrasound . The most common pathogenic copy number variants detected by microarray were 22q11.2 deletion, 22q11.2 duplication, 10q26.12q26.3 deletion, and 12q21q22 deletion, and approximately 1 percent were variants of uncertain significance.
These findings should be considered by patients with enlarged NT who choose to undergo secondary cfDNA screening. Since cfDNA screening only detects trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies, not performing an invasive procedure for more detailed genetic testing will fail to detect some genetic causes of enlarged NT.
Exome or genome sequencing — It is reasonable to offer screening for pathogenic variants associated with Noonan syndrome in cases of euploid fetuses with NT ≥3.0 mm, and this certainly should be considered when the NT is ≥5 mm given the strong association between very enlarged NT and RASopathies [10,11]. Noonan syndrome can present with enlarged NT, cystic hygroma, and/or congenital heart abnormalities and a euploid karyotype, but can be identified by targeted molecular genetic testing or exome sequencing of amniocytes or chorionic villi. In nonanomalous fetuses with enlarged NT >99th percentile, a meta-analysis found that exome or genome sequencing had a 4 percent incremental diagnostic yield over microarray . Among the 15 fetuses with a syndrome or other disorder identified by sequencing, Noonan syndrome accounted for four cases and was the only syndrome identified in more than one fetus. (See "Causes of short stature", section on 'Noonan syndrome'.)
First and second trimester fetal anatomic survey — An initial early anatomic survey is performed at the time of NT measurement. Experienced ultrasonographers using high-resolution transvaginal ultrasound can detect many major malformations in the first trimester . However, the sensitivity for diagnosis of congenital anomalies, especially cardiac anomalies, is higher at 18 to 22 weeks of gestation, and the survey should be repeated at that time.
Fetal echocardiography — Fetal echocardiography is performed at 18 to 22 weeks of gestation in fetuses with enlarged NT. Different thresholds for performing echocardiography have been suggested, and available data do not clearly support one threshold over another. The AIUM Practice Parameter for the Performance of Fetal Echocardiography suggests fetal echocardiography when NT is ≥3.5 mm or ≥99th percentile for gestational age . ACOG considers enlarged NT as ≥3.0 mm or >99th percentile for the crown-rump length .
Specialized centers can perform fetal echocardiography as early as 13 or 14 weeks of gestation with a complete cardiac evaluation possible in over 90 percent of cases . The sensitivity of early fetal echocardiography is over 50 percent in high-risk patients but not sufficiently high to allow omitting the 18 to 22 week evaluation if the early evaluation is normal . Its major benefit is early reassurance in at-risk pregnancies. If performed, the duration of interrogation should be as short as possible to limit fetal exposure to Doppler. (See "Congenital heart disease: Prenatal screening, diagnosis, and management".)
Third-trimester fetal assessment — There is an increased risk of fetal demise in fetuses with enlarged NT, particularly if persistent, even after correcting for associated chromosomal and structural abnormalities. No studies have specifically addressed the optimal management of these pregnancies after initial evaluation. Given these risks, we perform a fetal growth scan early in the third trimester and order antenatal fetal testing (nonstress test or biophysical profile) weekly starting at 36 weeks. However, if growth restriction is diagnosed, then surveillance is according to usual obstetric standards for monitoring these pregnancies. (See "Fetal growth restriction: Evaluation".)
Anatomy and pathogenesis — Cystic hygroma is a congenital malformation resulting from lymph accumulation in the jugular lymphatic sacs due to obstruction of the lymphatic system, most commonly in the fetal neck. Cystic hygromas may be septated or simple (nonseptated or biseptate).
Incidence — In the first trimester, the overall incidence of cystic hygroma is approximately 1 in 100 fetuses; the incidence of septated cystic hygroma is approximately 1 in 285 fetuses [12,54].
Prenatal diagnosis — Prenatal diagnosis of cystic hygroma is based on ultrasound examination, typically in the first trimester, showing a single or multilocular fluid-filled structure in the nuchal region or extending along the entire length of the fetus (image 3). When imaged in multiple planes, multiple internal septae or trabeculae may be identified (image 4A-B), and distended jugular lymph sacs may be visualized on either side of the fetal neck (image 5).
Differential diagnosis — Differential diagnosis of the ultrasound findings described above include:
●Enlarged NT – A biseptate nuchal fluid collection could represent either a simple cystic hygroma or enlarged NT with visualization of the midline ligamentum nuchae . Features that suggest a cystic hygroma are large size, extension of the lesion along the entire length of the fetus, and identification of multiple septae. The mean size of first-trimester cystic hygromas has been reported to be 8 mm with some measuring over 30 mm . Enlarged NT tends to be smaller than a cystic hygroma and more likely to be confined to the nuchal region between the occiput and upper spine . (See 'Prenatal diagnosis' above.)
●Neural tube defect – Both cystic hygromas and neural tube defects protrude from the fetal surface. Cystic hygroma can be distinguished from a neural tube defect, such as a posterior encephalocele or cervical meningocele, by visualizing an intact skull and spine on high-resolution transvaginal ultrasonography. (See "Neural tube defects: Prenatal sonographic diagnosis".)
●Cystic teratoma – A cystic hygroma can be distinguished from a cystic teratoma protruding from the fetal surface by the presence or absence of solid components in the lesion: A cystic hygroma has only cystic components while a cystic teratoma tends to have both cystic and solid components.
●Hemangioma – A cystic hygroma often has internal septae while a hemangioma does not. On color-flow mapping, a hemangioma will have robust vascularity whereas a cystic hygroma has only a limited vascular supply.
Clinical significance — Cystic hygromas are associated with an increased risk for fetal aneuploidy and structural malformations, both of which increase the risk for miscarriage, hydrops, fetal demise, and neonatal death. Increasing size is associated with an increasing risk of abnormal outcome [26,27,57]. Nuchal septations during first-trimester sonography is a risk factor for chromosomal anomalies, even in the absence of enlarged NT .
Aneuploidy — In the first trimester, cystic hygromas are associated with an increased risk for fetal trisomy, especially trisomy 21 [12,56]. In the second trimester, a cystic hygroma may be the clinical presentation of monosomy X .
Aneuploidy appears to be more frequent with septated than simple cystic hygromas. In one study, the frequency of aneuploidy with septated and simple cystic hygromas was 57 and 21 percent, respectively . In another study, however, 60 percent of simple cystic hygromas ≥2 mm were associated with an abnormal karyotype, with trisomy 21 occurring in one-fourth of cases . The lack of a standard definition of cystic hygroma and differences in cystic hygroma size among study populations likely contribute to disparities among studies in reported risk for aneuploidy.
Structural abnormalities — Approximately one-third of euploid fetuses with first-trimester septated cystic hygromas have major structural anomalies, primarily cardiac and skeletal [12,56].
Natural history — In euploid fetuses, over 80 percent of simple cystic hygromas resolve within four weeks of diagnosis, and the vast majority of these neonates are phenotypically normal . Septated cystic hygromas also often resolve between 15 and 30 weeks of gestation.
There may be a link between large cystic hygromas in utero and postnatal webbed neck, which can occur with Turner syndrome. Anecdotally, the author has seen newborns with thickened neck/redundant nuchal folds at birth who had large second-trimester cystic hygroma that resolved before birth.
Postdiagnostic evaluation — Postdiagnostic evaluation is the same as for enlarged NT. (See 'Postdiagnostic evaluation' above.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Prenatal screening and diagnosis".)
SUMMARY AND RECOMMENDATIONS
●Background – Some nuchal fluid is a normal finding in all first-trimester fetuses (image 2A); however, abnormal accumulations, such as a cystic hygroma or enlarged (increased) nuchal translucency (NT), are associated with an increased risk of chromosomal and structural abnormalities. (See 'Introduction' above.)
●Enlarged nuchal translucency
•Prenatal diagnosis – Prenatal diagnosis of enlarged NT is based on ultrasound measurement of the nuchal fluid space when the crown-rump length is 36 to 84 mm, which corresponds to approximately 10 to 14 weeks of gestation. The most commonly used thresholds for diagnosis of enlarged NT are the 95th and 99th percentiles for gestational age (NT normally increases with gestational age) (image 2B). Calculators are available online that enable clinicians to enter the crown-rump length and NT measurement to obtain the NT percentile. (See 'Prenatal diagnosis' above.)
-Enlarged NT has been associated with increased risks for aneuploidy (particularly trisomy 21) and structural abnormalities (particularly congenital heart disease), which can result in miscarriage, fetal demise, or neonatal death. Enlarged NT may also be associated with developmental and genetic syndromes and, in twins, twin-twin transfusion syndrome. The magnitude of enlarged NT is an important prognostic factor: the prognosis worsens with increasing NT. (See 'Clinical significance' above.)
-In normal fetuses, enlarged NT commonly resolves spontaneously by the second trimester. A large or persistent nuchal fluid accumulation appears to be a poor prognostic factor, even in euploid nonanomalous fetuses. (See 'Natural history' above.)
-Some studies have reported an increased prevalence (up to 8.7 percent) of neurodevelopmental delay in children with a fetal history of enlarged NT; however, others have found no excess risk of developmental delay in children with normal karyotype and no congenital malformations in those in whom increased first-trimester NT resolved. (See 'Genetic syndromes' above.)
•Postdiagnostic evaluation – After a prenatal diagnosis of enlarged NT, postdiagnostic evaluation includes:
-Genetic counseling, including options for fetal genetic testing. (See 'Genetic studies' above.)
Noonan syndrome or an associated RASopathy can present with enlarged NT (typically ≥3 mm), cystic hygroma, and/or congenital heart defects and a euploid karyotype, and can be identified by targeted molecular genetic testing or exome sequencing of amniocytes or chorionic villi. (See 'Exome or genome sequencing' above.)
-Fetal anatomic survey at the time of NT measurement and at 18 to 22 weeks of gestation. (See 'First and second trimester fetal anatomic survey' above.)
-Fetal echocardiography at 18 to 22 weeks of gestation. (See 'Fetal echocardiography' above.)
-Periodic assessment of fetal well-being. (See 'Third-trimester fetal assessment' above.)
•Cystic hygroma is a congenital malformation resulting from lymph accumulation in the jugular lymphatic sacs due to obstruction of the lymphatic system in the fetal neck. Cystic hygromas may be septated or simple (nonseptated or biseptate). (See 'Anatomy and pathogenesis' above.)
•Prenatal diagnosis of cystic hygroma is based on ultrasound examination, typically in the first trimester, showing a single or multilocular fluid-filled structure in the nuchal region or extending along the entire length of the fetus (image 3). When imaged in multiple planes, multiple internal septae or trabeculae may be identified (image 4A-B) and distended jugular lymph sacs may be visualized on either side of the fetal neck (image 5). (See 'Prenatal diagnosis' above.)
•Cystic hygromas are associated with an increased risk for fetal aneuploidy (particularly trisomy 21) and structural malformations (particularly congenital heart defects), both of which increase the risk for miscarriage, hydrops, fetal demise, and neonatal death. Increasing size is associated with an increasing risk of abnormal outcome. In general, the risk of aneuploidy and congenital anomalies is higher with cystic hygromas than enlarged NT (table 1). (See 'Clinical significance' above.)
•Fetal genetic analysis should be offered to any patient with a first-trimester cystic hygroma or significantly enlarged NT, given the relatively high risk of aneuploidy. (See 'Genetic studies' above.)
•Postdiagnostic evaluation of cystic hygroma is the same as for enlarged NT. (See 'Postdiagnostic evaluation' above.)
1 : Increased nuchal translucency and distended jugular lymphatic sacs on first-trimester ultrasound.
3 : The anatomy of nuchal translucency at 10-14 weeks gestation in fetuses with trisomy 21: An incredible medical mystery.
5 : Ductus venosus flow velocities in relation to the cardiac defects in first-trimester fetuses with enlarged nuchal translucency.
6 : First-trimester fetuses with increased nuchal translucency do not show altered intracardiac flow velocities.
7 : Why increased nuchal translucency is associated with congenital heart disease: a systematic review on genetic mechanisms.
10 : Prenatal ultrasound findings of rasopathies in a cohort of 424 fetuses: update on genetic testing in the NGS era.
15 : Maintaining quality assurance for nuchal translucency sonography in a prospective multicenter study: Results from the FASTER trial
16 : First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.
19 : Incidence of major structural cardiac defects associated with increased nuchal translucency but normal karyotype.
20 : Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester.
21 : Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation.
22 : Outcome and early childhood follow-up of chromosomally normal fetuses with increased nuchal translucency at 10-14 weeks' gestation.
25 : A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy.
26 : UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group.
29 : Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with increased nuchal translucency, tricuspid regurgitation and abnormal flow in ductus venosus.
30 : Relationship between nuchal translucency thickness and prevalence of major cardiac defects in fetuses with normal karyotype.
33 : Nuchal translucency and major congenital heart defects in fetuses with normal karyotype: a meta-analysis.
34 : Risk of selected structural abnormalities in infants after increased nuchal translucency measurement.
37 : Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review.
39 : Neurodevelopmental outcome at 2 years of corrected age in fetuses with increased nuchal translucency thickness and normal karyotype compared with matched controls.
41 : Discordance in nuchal translucency thickness in the prediction of severe twin-to-twin transfusion syndrome.
44 : Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study.
45 : Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening?
47 : Risk of Clinically Significant Chromosomal Microarray Analysis Findings in Fetuses With Nuchal Translucency From 3.0 mm Through 3.4 mm.
48 : Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis.
49 : Diagnostic yield of next-generation sequencing in fetuses with isolated increased nuchal translucency: systematic review and meta-analysis.
50 : AIUM Practice Parameter for the Performance of Detailed Diagnostic Obstetric Ultrasound Examinations Between 12 Weeks 0 Days and 13 Weeks 6 Days.
54 : First trimester diagnosis of cystic hygromata using transvaginal ultrasound and cytogenetic evaluation.
59 : Prognostic value of ultrasound findings of fetal cystic hygroma detected in early pregnancy by transvaginal sonography.
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