First-trimester cystic hygroma and increased nuchal translucency
- Lynn L Simpson, MD
Lynn L Simpson, MD
- Professor of Obstetrics and Gynecology
- Columbia University College of Physicians and Surgeons
- Section Editors
- Deborah Levine, MD
Deborah Levine, MD
- Section Editor — Imaging
- Professor of Radiology
- Director of Ob/Gyn Ultrasound
- Department of Radiology
- Beth Israel Deaconess Medical Center
- Louise Wilkins-Haug, MD, PhD
Louise Wilkins-Haug, MD, PhD
- Section Editor — Prenatal Diagnosis and Genetics
- Professor of Obstetrics, Gynecology, and Reproductive Biology
- Harvard Medical School
Prenatal ultrasound screening in early pregnancy involves an assessment of the nuchal region of the fetus. Although a small hypoechoic space in the posterior fetal neck is a normal finding in all first-trimester fetuses, excessive enlargement is associated with an increased risk of Down syndrome, as well as other fetal abnormalities. Excessive enlargement may be related to a cystic hygroma or to mesenchymal edema (termed increased nuchal translucency).
The diagnosis and clinical significance of first-trimester cystic hygroma and increased nuchal translucency will be reviewed here. A detailed discussion of first-trimester screening for Down syndrome and other aneuploidies is provided separately. (See "First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18".)
Additional first-trimester markers and second-trimester ultrasound markers of aneuploidy are also reviewed separately. (See "Sonographic findings associated with fetal aneuploidy".)
ANATOMY AND PATHOGENESIS OF NUCHAL ABNORMALITIES
Cystic hygroma — Cystic hygroma is a congenital malformation of the lymphatic system in which obstruction between the lymphatic and venous pathways in the fetal neck leads to lymph accumulation in the jugular lymphatic sacs of the nuchal region. Cystic hygromas can be subclassified as septated or nonseptated (simple). In the first trimester, the overall prevalence of septated and nonseptated cystic hygromas is about 1 in 100 fetuses, and the prevalence of septated cystic hygromas is 1 in 285 fetuses [1,2].
Nuchal translucency — Nuchal translucency is the hypoechoic region located between the skin and soft tissues behind the cervical spine. This hypoechoic space is presumed to represent mesenchymal edema and is often associated with distended jugular lymphatics [3,4]. 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). On the other hand, increased nuchal translucency can be associated with a wide range of abnormalities or a normal fetus, which suggests that there are different pathophysiologic pathways that lead to the common end-point of increased nuchal fluid. The pathogenesis of nuchal edema is unknown, but probably multifactorial. It may involve fluid retention with hemodynamic disturbance, delayed or disturbed lymphangiogenesis, cardiac and vascular structural and functional abnormalities, and abnormal extracellular matrix components [5,6].
- Podobnik M, Singer Z, Podobnik-Sarkanji S, Bulić M. First trimester diagnosis of cystic hygromata using transvaginal ultrasound and cytogenetic evaluation. J Perinat Med 1995; 23:283.
- Malone FD, Ball RH, Nyberg DA, et al. First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome. Obstet Gynecol 2005; 106:288.
- Bekker MN, Haak MC, Rekoert-Hollander M, et al. Increased nuchal translucency and distended jugular lymphatic sacs on first-trimester ultrasound. Ultrasound Obstet Gynecol 2005; 25:239.
- Haak MC, van Vugt JM. Pathophysiology of increased nuchal translucency: a review of the literature. Hum Reprod Update 2003; 9:175.
- Nafziger E, Vilensky JA. The anatomy of nuchal translucency at 10-14 weeks gestation in fetuses with trisomy 21: An incredible medical mystery. Clin Anat 2014; 27:353.
- Allan LD. The mystery of nuchal translucency. Cardiol Young 2006; 16:11.
- Nicolaides KH. First-trimester screening for chromosomal abnormalities. Semin Perinatol 2005; 29:190.
- Bronshtein M, Zimmer EZ, Blazer S. A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy. Am J Obstet Gynecol 2003; 188:1016.
- Haak MC, Twisk JW, Bartelings MM, et al. Ductus venosus flow velocities in relation to the cardiac defects in first-trimester fetuses with enlarged nuchal translucency. Am J Obstet Gynecol 2003; 188:727.
- Matias A, Gomes C, Flack N, et al. Screening for chromosomal abnormalities at 10-14 weeks: the role of ductus venosus blood flow. Ultrasound Obstet Gynecol 1998; 12:380.
- Haak MC, Twisk JW, Bartelings MM, et al. First-trimester fetuses with increased nuchal translucency do not show altered intracardiac flow velocities. Ultrasound Obstet Gynecol 2005; 25:246.
- Martínez JM, Echevarría M, Gómez O, et al. Jugular vein and carotid artery blood flow in fetuses with increased nuchal translucency at 10-14 weeks' gestation. Ultrasound Obstet Gynecol 2003; 22:464.
- Simpson JM, Sharland GK. Nuchal translucency and congenital heart defects: heart failure or not? Ultrasound Obstet Gynecol 2000; 16:30.
- Scott A. Nuchal translucency measurement in first trimester Down syndrome screening. Issues Emerg Health Technol 2007; :1.
- Wapner R, Thom E, Simpson JL, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med 2003; 349:1405.
- D'Alton ME, Malone FD, Lambert-Messerlian G, et al. Maintaining quality assurance for nuchal translucency sonography in a prospective multicenter study: Results from the FASTER trial. Am J Obstet Gynecol 2003; 189:S79.
- Snijders RJ, Thom EA, Zachary JM, et al. First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique. Ultrasound Obstet Gynecol 2002; 19:353.
- Molina FS, Avgidou K, Kagan KO, et al. Cystic hygromas, nuchal edema, and nuchal translucency at 11-14 weeks of gestation. Obstet Gynecol 2006; 107:678.
- Graesslin O, Derniaux E, Alanio E, et al. Characteristics and outcome of fetal cystic hygroma diagnosed in the first trimester. Acta Obstet Gynecol Scand 2007; 86:1442.
- Rosati P, Guariglia L. Prognostic value of ultrasound findings of fetal cystic hygroma detected in early pregnancy by transvaginal sonography. Ultrasound Obstet Gynecol 2000; 16:245.
- Johnson MP, Johnson A, Holzgreve W, et al. First-trimester simple hygroma: cause and outcome. Am J Obstet Gynecol 1993; 168:156.
- Snijders RJ, Noble P, Sebire N, et al. 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. Lancet 1998; 352:343.
- Kagan KO, Avgidou K, Molina FS, et al. Relation between increased fetal nuchal translucency thickness and chromosomal defects. Obstet Gynecol 2006; 107:6.
- Mangione R, Guyon F, Taine L, et al. Pregnancy outcome and prognosis in fetuses with increased first-trimester nuchal translucency. Fetal Diagn Ther 2001; 16:360.
- Pandya PP, Kondylios A, Hilbert L, et al. Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency. Ultrasound Obstet Gynecol 1995; 5:15.
- Atzei A, Gajewska K, Huggon IC, et al. Relationship between nuchal translucency thickness and prevalence of major cardiac defects in fetuses with normal karyotype. Ultrasound Obstet Gynecol 2005; 26:154.
- Simpson LL, Malone FD, Bianchi DW, et al. Nuchal translucency and the risk of congenital heart disease. Obstet Gynecol 2007; 109:376.
- Sotiriadis A, Papatheodorou S, Eleftheriades M, Makrydimas G. Nuchal translucency and major congenital heart defects in fetuses with normal karyotype: a meta-analysis. Ultrasound Obstet Gynecol 2013; 42:383.
- Jelliffe-Pawlowski LL, Norton ME, Shaw GM, et al. Risk of critical congenital heart defects by nuchal translucency norms. Am J Obstet Gynecol 2015; 212:518.e1.
- Sciarrone A, Masturzo B, Botta G, et al. First-trimester fetal heart block and increased nuchal translucency: an indication for early fetal echocardiography. Prenat Diagn 2005; 25:1129.
- Favre R, Cherif Y, Kohler M, et al. The role of fetal nuchal translucency and ductus venosus Doppler at 11-14 weeks of gestation in the detection of major congenital heart defects. Ultrasound Obstet Gynecol 2003; 21:239.
- Maiz N, Plasencia W, Dagklis T, et al. Ductus venosus Doppler in fetuses with cardiac defects and increased nuchal translucency thickness. Ultrasound Obstet Gynecol 2008; 31:256.
- Papatheodorou SI, Evangelou E, Makrydimas G, Ioannidis JP. First-trimester ductus venosus screening for cardiac defects: a meta-analysis. BJOG 2011; 118:1438.
- Pereira S, Ganapathy R, Syngelaki A, et al. Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects. Obstet Gynecol 2011; 117:1384.
- Burger NB, Bekker MN, de Groot CJ, et al. Why increased nuchal translucency is associated with congenital heart disease: a systematic review on genetic mechanisms. Prenat Diagn 2015; 35:517.
- Baer RJ, Norton ME, Shaw GM, et al. Risk of selected structural abnormalities in infants after increased nuchal translucency measurement. Am J Obstet Gynecol 2014; 211:675.e1.
- Sebire NJ, Snijders RJ, Hughes K, et al. Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. Br J Obstet Gynaecol 1996; 103:999.
- Sebire NJ, Souka A, Skentou H, et al. Early prediction of severe twin-to-twin transfusion syndrome. Hum Reprod 2000; 15:2008.
- Kagan KO, Gazzoni A, Sepulveda-Gonzalez G, et al. Discordance in nuchal translucency thickness in the prediction of severe twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2007; 29:527.
- El Kateb A, Nasr B, Nassar M, et al. First-trimester ultrasound examination and the outcome of monochorionic twin pregnancies. Prenat Diagn 2007; 27:922.
- Bilardo CM, Timmerman E, Pajkrt E, van Maarle M. Increased nuchal translucency in euploid fetuses--what should we be telling the parents? Prenat Diagn 2010; 30:93.
- Pergament E, Alamillo C, Sak K, Fiddler M. Genetic assessment following increased nuchal translucency and normal karyotype. Prenat Diagn 2011; 31:307.
- Souka AP, Von Kaisenberg CS, Hyett JA, et al. Increased nuchal translucency with normal karyotype. Am J Obstet Gynecol 2005; 192:1005.
- Ducarme G, Graesslin O, Alanio E, et al. [Increased nuchal translucency and cystic hygroma in the first trimester: prenatal diagnosis and neonatal outcome]. Gynecol Obstet Fertil 2005; 33:750.
- Scholl J, Durfee SM, Russell MA, et al. First-trimester cystic hygroma: relationship of nuchal translucency thickness and outcomes. Obstet Gynecol 2012; 120:551.
- Zoppi MA, Ibba RM, Floris M, et al. Changes in nuchal translucency thickness in normal and abnormal karyotype fetuses. BJOG 2003; 110:584.
- Maymon R, Weinraub Z, Herman A. Pregnancy outcome of euploid fetuses with increased nuchal translucency: how bad is the news? J Perinat Med 2005; 33:191.
- Ghi T, Huggon IC, Zosmer N, Nicolaides KH. Incidence of major structural cardiac defects associated with increased nuchal translucency but normal karyotype. Ultrasound Obstet Gynecol 2001; 18:610.
- Souka AP, Krampl E, Bakalis S, et al. Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound Obstet Gynecol 2001; 18:9.
- Souka AP, Snijders RJ, Novakov A, et al. Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. Ultrasound Obstet Gynecol 1998; 11:391.
- Van Vugt JM, Tinnemans BW, Van Zalen-Sprock RM. Outcome and early childhood follow-up of chromosomally normal fetuses with increased nuchal translucency at 10-14 weeks' gestation. Ultrasound Obstet Gynecol 1998; 11:407.
- Bilardo CM, Müller MA, Pajkrt E, et al. Increased nuchal translucency thickness and normal karyotype: time for parental reassurance. Ultrasound Obstet Gynecol 2007; 30:11.
- Sotiriadis A, Papatheodorou S, Makrydimas G. Neurodevelopmental outcome of fetuses with increased nuchal translucency and apparently normal prenatal and/or postnatal assessment: a systematic review. Ultrasound Obstet Gynecol 2012; 39:10.
- Cleary-Goldman J, D'Alton ME, Berkowitz RL. Prenatal diagnosis and multiple pregnancy. Semin Perinatol 2005; 29:312.
- Chitty LS, Kagan KO, Molina FS, et al. Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study. BMJ 2006; 332:452.
- Comstock CH, Malone FD, Ball RH, et al. Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening? Am J Obstet Gynecol 2006; 195:843.
- Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med 2005; 353:2001.
- Leung TY, Vogel I, Lau TK, et al. Identification of submicroscopic chromosomal aberrations in fetuses with increased nuchal translucency and apparently normal karyotype. Ultrasound Obstet Gynecol 2011; 38:314.
- Huang J, Poon LC, Akolekar R, et al. Is high fetal nuchal translucency associated with submicroscopic chromosomal abnormalities on array CGH? Ultrasound Obstet Gynecol 2014; 43:620.
- Grande M, Jansen FA, Blumenfeld YJ, et al. Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015; 46:650.
- Haak MC, van Vugt JM. Echocardiography in early pregnancy: review of literature. J Ultrasound Med 2003; 22:271.
- ANATOMY AND PATHOGENESIS OF NUCHAL ABNORMALITIES
- Cystic hygroma
- Nuchal translucency
- PRENATAL DIAGNOSIS
- Diagnosis of cystic hygroma
- Diagnosis of nuchal translucency
- Cystic hygroma or increased nuchal translucency?
- Differential diagnosis
- ASSOCIATED ABNORMALITIES
- Structural anomalies
- - Cardiac
- - Noncardiac
- Twin-to-twin transfusion
- Developmental and genetic syndromes
- Cystic hygroma
- Nuchal translucency
- - Multiple gestation
- OBSTETRICAL MANAGEMENT
- SUMMARY AND RECOMMENDATIONS