Sonographic Detection of Aneuploidy

1. Sonographic Detection of Aneuploidy Eric H. Dellinger, MD Director, Division of Maternal-Fetal Medicine Greenville Hospital System Greenville, South Carolina

2. Introduction • The Future of Science and Medicine: Exploring the extremes

7. Evolution of Ultrasound

11. Aneuploidy

13. Benefits of Early Detection • Privacy issues • Decreased maternal bonding • Safer pregnancy termination • Higher detection rate

14. Nuchal Translucency • Clear space in posterior neck • Imaged between 11 and 14 weeks or when CRL is 36 to 84 mm • Nuchal thickening is associated with: • Aneuploidy • Anomalies • Infections • Metabolic and hematologic disorders

15. Incidence of chromosomal defects Nuchal translucency (mm) Total n Chromosomal defects (%) < 3.4 95,086 0.33 3.5 - 4.4 568 21.12 4.5 - 5.4 207 33.33 5.5 - 6.4 97 50.51 > 6.5 166 64.45 Snijders et al. 1998

16. Trisomy 21 Detection Rate • 96,127 patients studied • NT and age • Median age 31 years • 5% screen positive rate • 77% of affected fetuses detected Snijders et al, Lancet 1998; 352: 343.

17. Other Associations • Genetic syndromes: • Cornelia de Lange, Noonan, Smith-Lemli-Opitz, Apert • Anomalies: • Cardiac, diaphragmatic hernia • Adverse outcome: • Early demise • Targeted scan indicated if euploid

18. Cardiac defects Diaphragmatic hernia Omphalocele Duodenal atresia Esophageal atresia Skeletal dysplasias Lethal congenital arthryogryposis Smith-Lemli-Optiz syndrome Megacystis Fryn syndrome Joubert syndrome Meckel-Gruber syndrome VATER association Anomalies with Increased NT

19. NT and CHD • In 29,154 chromosomally normal fetuses, 56% of major abnormalities of the heart and great arteries were found in the subgroup with nuchal translucency above the 95th centile. • Nuchal translucency thickness at 11–14 weeks may constitute the most effective method of screening for cardiac defects. Hyett JA, et al, Br Med J 1999:318:81–5

20. NT and Cardiac Defects NT CHD per 1000 < 2.0 mm 1.9 2.0 to 2.4 mm 4.8 2.5 to 3.4 mm 6.0 > 3.4 mm 23 Bahado-Singh et al, Am J Obstet Gynecol. 2005 May;192(5):1357-61

21. NT Technique

22. Proper CRL is a MSLL MSLL = maximum straight line length

23. Enlarge

25. Caliper Placement

26. NT Increase at 11 – 14 weeks

27. NT Interpretation From 10 - 14 weeks, the 99th percentile remains constant at 3.5 millimeters, independent of gestational age or crown-rump length. Nicolaides , Semin Perinatol. 2005;29(4):190.

28. NT measurement in 326 trisomy 21 fetuses

29. NT thickness and chromosomal abnormalities other than trisomy 21

30. Adverse Outcome with Increased NT NT Poor Outcome 3.5 - 4.4 mm 32% 4.5 - 5.4 mm 49% 5.5 - 6.4 mm 67% > 6.5 mm 89% Ultrasound Obstet Gynecol 2001;18:9-17

31. Cutoff • 3 mm threshold identifies 80% of Downs • 5% SPR • High risk population • 95th percentile is a better threshold • NT between 95th and 99th percentile carries 3.7% risk of aneuploidy Br J ObGyn 1994; 101:782 Lancet 1998; 352: 343

32. Pitfalls

33. Beware • NT cannot be obtained in all patients (~6%) • Fetal position • Maternal body habitus • Time constraints (allot 20 min) • Identify the amnion • Nuchal thickening may decrease over time

34. Essential for proper NT • Magnify the image until the fetal head and thorax occupy the whole screen. • Obtain a mid-sagittal view of the face. Minor deviations: non-visualization of the tip of the nose and visibility of the zygomatic process of the maxilla. • The fetus should be in a neutral position.

35. Essential for proper NT • Widest part of NT must be measured. • The crossbar of the calliper should be such that it is hardly visible as it merges with the white line of the border, not in the nuchal fluid. • Turn the gain down. This helps avoid placing the calliper on the fuzzy edge of the line which can underestimate the nuchal measurement.

36. Amnion vs. NT

37. Nasal Bone

38. Nasal Bone • Conflicting results in European vs. US studies • May reflect the technical difficulty of imaging • Review of over 35,000 nasal bone exams from 9 studies: • Successful study in 94.3% • Absent in 65% of Downs (0.8% of normals) Obstet Gynecol 2007; 110:300

39. Nasal Bone • The optimum time for nasal bone assessment is at crown rump length of 65 to 74 mm (13 to 13.5 weeks of gestation). • Absent nasal bone earlier in gestation could reflect delayed maturation, rather than actual absence of the structure. Ville, Am J Obstet Gynecol. 2006;195(1):1.

40. Cystic Hygroma

41. Doppler Umbilical Ductus

43. Tricuspid Regurgitation Normal Tricuspid Regurgitation

45. Anomalies and Aneuploidy Normal newborns 0.5% aneuploid Structural anomalies 11% aneuploid Am J Med Genet 1988;29:289

46. Type of Defect Matters Omphalocele with liver 3 of 34 aneuploid Omphalocele without liver 12 of 14 aneuploid AJR 1992;158:133; J Ultra Med 1989;8:299

47. Growth Restriction FindingAneuploid Isolated IUGR 2 % IUGR + anomaly 20 % Am J Obstet Gynecol 1993;168:547

48. Detecting Down Syndrome

49. Major Malformation • 33% of Down fetuses have one or more major malformations • Heart • CNS • GI • Face/neck • Hydrops Ped Clin N Am 1984;31:1331

50. Cardiovascular • 40-50% manifest heart anomalies