nuchal translucency in first-trimester ultrasound screening for

Nuchal Translucency in Nuchal Translucency in FirstFirst--Trimester Ultrasound Trimester Ultrasound Screening for Trisomy 21Screening for Trisomy 21

Jane Serene, MS3Jane Serene, MS3Core Radiology Clerkship Core Radiology Clerkship

Beth Israel Deaconess Medical CenterBeth Israel Deaconess Medical Center

“Nuchal translucency“Nuchal translucency--based screening based screening for fetal abnormalities has truly for fetal abnormalities has truly

become an indispensable aspect of become an indispensable aspect of contemporary obstetric practice.”contemporary obstetric practice.”(Soha Said, (Soha Said, Clinical Obstetrics and Gynecology, Clinical Obstetrics and Gynecology, March 2008)March 2008)

AgendaAgendaIntroduction to Our PatientsIntroduction to Our PatientsDefinition of Nuchal Translucency and Definition of Nuchal Translucency and Measurement Criteria Measurement Criteria NT in Trisomy 21 ScreeningNT in Trisomy 21 ScreeningAdvantages/Limitations of NT ScreeningAdvantages/Limitations of NT ScreeningDifferential Diagnosis of Increased NTDifferential Diagnosis of Increased NTMechanisms of Increased NTMechanisms of Increased NTFetal Anomalies associated with Increased NTFetal Anomalies associated with Increased NTFollowFollow--up on Our Patientsup on Our Patients

Two Patients With Increased Fetal Risk for Two Patients With Increased Fetal Risk for Trisomy 21Trisomy 21

Our First PatientOur First Patient

41 year41 year--old, G5P2, with old, G5P2, with singleton pregnancysingleton pregnancy

Presents for early OB Presents for early OB ultrasound (<14 weeks) ultrasound (<14 weeks)

Nuchal translucency = Nuchal translucency = 4mm 4mm

Our Second PatientOur Second Patient

40 year40 year--old, G3P1, with old, G3P1, with singleton pregnancysingleton pregnancy

Presents for early OB Presents for early OB ultrasoundultrasound

Nuchal translucency = Nuchal translucency = 2.7mm2.7mm

Defining Nuchal TranslucencyDefining Nuchal TranslucencyFluid between skin and Fluid between skin and

soft tissue at back of fetal soft tissue at back of fetal neckneck

Can be seen Can be seen sonographically in all first sonographically in all first trimester fetuses trimester fetuses

Criteria for Criteria for IncreasedIncreased NT: NT: --NT > 3mmNT > 3mm--Depends on gestational Depends on gestational age (Most accurately age (Most accurately expressed as multiple of expressed as multiple of the median) the median) [3][3]

PACS, BIDMC

Trans-abdominal OB U/S, sagittal view

Increased NT

Criteria for NT Measurement (1)Criteria for NT Measurement (1)

1.Crown1.Crown--Rump Length = 45Rump Length = 45--84mm (approximately 1184mm (approximately 11--14wks).14wks).2.Mid2.Mid--sagittal plane with fetus in neutral position: sagittal plane with fetus in neutral position: Neck flexion decreases NT; Neck extension increases NT.Neck flexion decreases NT; Neck extension increases NT.

PACS, BIDMC


Criteria for NT Measurement (2)Criteria for NT Measurement (2)

3.Enlarge image: upper 2/3 of fetus. 3.Enlarge image: upper 2/3 of fetus. 4.Identify potential false positives: non4.Identify potential false positives: non--fused amnion, nuchal fused amnion, nuchal cord, neck extension.cord, neck extension.5.Measure maximal translucency in greatest dimension: 5.Measure maximal translucency in greatest dimension: from outer soft tissue edge to inner nuchal membrane edge.from outer soft tissue edge to inner nuchal membrane edge.

PACS, BIDMC


Findings:

1. Nasal Bone

2. Chin

3. Increased NT (4.2mm)

Inaccurate NT MeasurementInaccurate NT Measurement

BIDMC-PACS


1. Not midline view: Nasal bone and chin not visible.

2. Difficult to separate fetal skin from amnion.

How does Nuchal How does Nuchal Translucency fit into Translucency fit into

screening for Trisomy 21? screening for Trisomy 21?

The Combined TestThe Combined Test

Nuchal Translucency measurement Nuchal Translucency measurement between 11between 11--14 weeks14 weeks

Maternal Serum MarkersMaternal Serum Markers1.Free beta1.Free beta--hCG: Elevated in T21hCG: Elevated in T21

2.Pregnancy2.Pregnancy--associated plasma protein A associated plasma protein A (PAPP(PAPP--A): Decreased in T21A): Decreased in T21

Practice Guidelines for Trisomy 21 ScreeningPractice Guidelines for Trisomy 21 Screening

ACOG 2007: All women should be offered ACOG 2007: All women should be offered aneuploidy screening before 20wks gestation. aneuploidy screening before 20wks gestation. --using maternal age alone to triage patients into diagnostic testusing maternal age alone to triage patients into diagnostic testing ing misses 50% of T21 pregnancies that occur in women <35 misses 50% of T21 pregnancies that occur in women <35 y/oy/o..--noninvasive screening tests enable women to be more certain of tnoninvasive screening tests enable women to be more certain of their heir actual risk for T21, which they can then weigh against the risk actual risk for T21, which they can then weigh against the risk of of invasive diagnostic testing. invasive diagnostic testing.

Ideal Screening: “Combined Test” in First Ideal Screening: “Combined Test” in First Trimester with followTrimester with follow--up depending on results.up depending on results.

Choose type of screening based on tests Choose type of screening based on tests available in your area, patient’s wishes, and available in your area, patient’s wishes, and patient’s risk factors.patient’s risk factors.“ACOG Practice Bulletin 77: Screening for Fetal Chromosomal Abnormalities.” Obstetrics and Gynecology.

109:1. Jan. 2007.

Comparing Screening Methods for T21Comparing Screening Methods for T21Gestational AgeGestational Age Detection Detection

Rate/SensitivityRate/SensitivityFalse Positive False Positive

RateRate

Nuchal Translucency + Nuchal Translucency + Maternal AgeMaternal Age 1111--14 weeks14 weeks 7272--77%77% 4.24.2--5%5%

Combined Test: Age + Combined Test: Age + NT + PAPPNT + PAPP--A + BetaA + Beta--

hCGhCG1111--14 weeks14 weeks 85%85% 4.84.8

Full Integrated Test: Full Integrated Test: Combined Test + Quad Combined Test + Quad

ScreenScreen

1111--14 weeks + 14 weeks + 1515--18 weeks18 weeks

85%85%9090--95%95%

1%1%2.62.6--5%5%

Serum Integrated Test: Serum Integrated Test: PAPPPAPP--A + Quad A + Quad Screen (No U/S)Screen (No U/S)

1111--14 weeks +14 weeks +1515--18 weeks18 weeks

85%85% 3.5%3.5%

Quad Screen: serum Quad Screen: serum AFP, uE3, AFP, uE3,

hCG, inhibin AhCG, inhibin A1515--18 weeks18 weeks 85%85% 6.8%6.8%

*All data from FASTER (First and Second Trimester Evaluation of Risk) and SURUSS (Serum, Urine and Ultrasound Screening Study) Trials.

Barss VA et al. “Overview of prenatal screening for Down syndrome.” UpToDate 16.1. <http://tudol.com>

Advantages of Screening with Advantages of Screening with The Combined TestThe Combined Test

Abnormal TestAbnormal TestFirstFirst--trimester identification trimester identification

of patients at highof patients at high--risk for risk for fetal anomalies. fetal anomalies. --Allows for early therapeutic Allows for early therapeutic abortion.abortion.--Enables preEnables pre--natal planning natal planning for care of affected child. for care of affected child.

Triage patients for further Triage patients for further testing, which improves testing, which improves costcost--effective use of effective use of resources. resources.

Normal TestNormal TestLowers overall risk of Lowers overall risk of

advanced maternal age advanced maternal age patients. patients. --Decreases use of invasive Decreases use of invasive diagnostic procedures diagnostic procedures (CVS, amniocentesis)(CVS, amniocentesis)--Decreases procedureDecreases procedure-- associated fetal loss. associated fetal loss.

Reduces anxiety.Reduces anxiety.

Limitations of The Combined Test Limitations of The Combined Test

NT measurement is operator dependent and NT measurement is operator dependent and requires special training. requires special training. A significant number of patients do not get A significant number of patients do not get prenatal care until the 2prenatal care until the 2ndnd trimester.trimester.20% of obstetric patients are not being offered 20% of obstetric patients are not being offered this test in spite of research demonstrating its this test in spite of research demonstrating its efficacy. efficacy. AnxietyAnxiety--provoking when positive. If patients do provoking when positive. If patients do not want CVS, they must wait 4 weeks for not want CVS, they must wait 4 weeks for amniocentesis. amniocentesis.

You identify a neck mass You identify a neck mass during first trimester during first trimester

ultrasound screening. What ultrasound screening. What do you need to rule out do you need to rule out

before diagnosing increased before diagnosing increased nuchal translucency? nuchal translucency?

Differential Diagnosis: 1Differential Diagnosis: 1stst Trimester Neck MassTrimester Neck Mass

••Hydrops fetalisHydrops fetalis••Cystic HygromaCystic Hygroma••Nonfused amnionNonfused amnion••Nuchal cord Nuchal cord

Less Common: Branchial Less Common: Branchial cleft cyst, hemangioma, cleft cyst, hemangioma, neuroblastoma.neuroblastoma.

Courtesy of Koeller KK, et al. “Congenital Cystic Masses of the Neck: Radiologic-Pathologic Correlation.” Radiographics, 1999;19:121-146.

Trans-abdominal OB U/S, axial view of fetal head

Septated Cystic Hygroma

Potential Mechanisms for Potential Mechanisms for Increased Nuchal TranslucencyIncreased Nuchal Translucency

1.Heart strain/failure

2.Abnormal lymphatic drainage – increased # or size of lymphatics, irregular connection between lymphatics and veins, impaired fetal movement.

3.Abnormal extracellular matrix

PACS, BIDMC


Fetal Abnormalities Associated with Fetal Abnormalities Associated with Increased NTIncreased NT

Chromosomally AbnormalChromosomally AbnormalTrisomy 13Trisomy 13Trisomy 18Trisomy 18Trisomy 21Trisomy 21

Turner’s SyndromeTurner’s SyndromeTriploidyTriploidy

Unbalanced translocationsUnbalanced translocations

Chromosomally NormalChromosomally NormalCNS defectsCNS defects

Diaphragmatic herniaDiaphragmatic herniaOmphaloceleOmphalocele

Myotonic DystrophyMyotonic DystrophyEsophageal AtresiaEsophageal Atresia

Infantile PCKDInfantile PCKDAchondroplasia Achondroplasia Fetal AnemiaFetal Anemia

Metabolic defectsMetabolic defects(and others)(and others)

Increased NT and Fetal Abnormalities: Increased NT and Fetal Abnormalities: An Important CaveatAn Important Caveat

Increased NT is NOT a fetal anomaly in and of itself.Increased NT is NOT a fetal anomaly in and of itself.

90% of chromosomally normal fetuses with NT<4.5mm go 90% of chromosomally normal fetuses with NT<4.5mm go on to be healthy, liveon to be healthy, live--born infants.born infants.

If there are no abnormalities on targeted ultrasound at 20If there are no abnormalities on targeted ultrasound at 20--22 22 weeks, there is no increased risk of poor outcome. weeks, there is no increased risk of poor outcome.

There is no increased prevalence of developmental delay There is no increased prevalence of developmental delay associated with increased NT.associated with increased NT.

Back to Our First PatientBack to Our First Patient

Patient 1: Fetal Ultrasound

•41 y/o G5P2

•Sent for early OB ultrasound to evaluate NT secondary to Advanced Maternal Age

•PAPP-A and beta-hCG levels unknown

•CRL =55.2mmPACS, BIDMC


Patient 1: NT Measurement on Fetal USPatient 1: NT Measurement on Fetal US

PACS, BIDMC

Trans-abdominal OB U/S, midline sagittal view

NT = 4.1mm

Outcome for Our First Patient: Outcome for Our First Patient: Trisomy 21Trisomy 21

Final NT Measurement = 4.0mmFinal NT Measurement = 4.0mm

FollowFollow--up:up:1.Amniocentesis at 16 weeks: 1.Amniocentesis at 16 weeks: 47, XX, +2147, XX, +21

2.Full Fetal Survey at 21w6d: 2.Full Fetal Survey at 21w6d: common AV canal.3.Ultrasound at 33w2d: 3.Ultrasound at 33w2d: size<dates,

oligohydramnios, no duodenal atresia., no duodenal atresia.4.Uncomplicated delivery at 38w6d. 4.Uncomplicated delivery at 38w6d.

Patient 2: Fetal Ultrasound

•40 y/o G3P1

• Combined Test Results: 1.Decreased PAPP-A 2.Increased hCG 3.Ultrasound -CRL = 63.6mm

PACS, BIDMC


Patient 2: NT Measurement on Fetal USPatient 2: NT Measurement on Fetal US

PACS, BIDMC

NT = 2.7mm

Trans-abdominal OB U/S, midline sagittal view

Outcome for Our Second Patient: Outcome for Our Second Patient: Normal FetusNormal Fetus

Final NT Measurement= 2.6mmFinal NT Measurement= 2.6mm

FollowFollow--up:up:1.Full Fetal Survey at 16w0d: No abnormalities.1.Full Fetal Survey at 16w0d: No abnormalities.

2.Patient declined amniocentesis.2.Patient declined amniocentesis.3.Quad Screen at 19w1d: Lowered T21 risk 3.Quad Screen at 19w1d: Lowered T21 risk

4.Delivered healthy baby girl at 40w5d. 4.Delivered healthy baby girl at 40w5d.

Summary Summary Nuchal Translucency, as part of the Combined Test, is an Nuchal Translucency, as part of the Combined Test, is an

effective and accurate method of screening for fetal effective and accurate method of screening for fetal anomalies, especially Trisomy 21. anomalies, especially Trisomy 21.

Sensitive, nonSensitive, non--invasive screening tests ensure that only invasive screening tests ensure that only those pregnancies at highthose pregnancies at high--risk for abnormalities undergo risk for abnormalities undergo invasive diagnostic procedures.invasive diagnostic procedures.

Ultrasonographers must be carefully trained in NT Ultrasonographers must be carefully trained in NT measurement. measurement.

All women who receive aneuploidy screening should be All women who receive aneuploidy screening should be appropriately counseled and provided with thorough followappropriately counseled and provided with thorough follow-- up.up.

AcknowledgementsAcknowledgements

Dr. Hope Dr. Hope RicciottiRicciottiMaria LevantakisMaria LevantakisDr. Prachi DubeyDr. Prachi DubeyDr. Rola ShaheenDr. Rola ShaheenDr. Colin McCardleDr. Colin McCardleDr. Gail BirchDr. Gail BirchDr. Gillian LiebermanDr. Gillian Lieberman

ResourcesResources

““ACOG Practice Bulletin 77: Screening for Fetal Chromosomal AbnorACOG Practice Bulletin 77: Screening for Fetal Chromosomal Abnormalities.” malities.” Obstetrics and Obstetrics and Gynecology, 109:1.Gynecology, 109:1. Jan. 2007. Jan. 2007.

Barss VA, et al. “Overview of prenatal screening for Down syndroBarss VA, et al. “Overview of prenatal screening for Down syndrome.” me.” UpToDate 16.1UpToDate 16.1. (5/23/08). (5/23/08)Benacerraf, BR. “The sonographic diagnosis of fetal aneuploidy.”Benacerraf, BR. “The sonographic diagnosis of fetal aneuploidy.” UpToDate 16.1. (5/16/08)UpToDate 16.1. (5/16/08)Jackson M and Rose NC. “Diagnosis and Management of Fetal NuchalJackson M and Rose NC. “Diagnosis and Management of Fetal Nuchal Translucency.” Translucency.” Seminars Seminars

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nuchal translucency in first-trimester ultrasound screening for

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