Absent Nasal Bone in the Fetus

Background / Pathophysiology

When and How It Is Assessed

First Trimester (11-13+6 weeks)

• Image magnified so each caliper movement = 0.1 mm change
• Midsagittal view of fetal profile (tip of nose, 3rd/4th ventricles visible; orbit and zygoma NOT seen)
• Transducer parallel to the direction of the nose, tilted side-to-side to confirm NB is separate from overlying skin

Note: The echogenic skin edge can be mistaken for the nasal bone. Careful tilting technique is essential.

Ultrasound Images

Performance as a Screening Marker

First Trimester

Second Trimester

• Hypoplastic or absent NB occurs in up to 60% of Down syndrome pregnancies imaged in the second trimester
  • Complete absence: ~37% of affected cases
  • Hypoplasia: ~50% of affected cases
• In normal pregnancies: absence in 0.9%, hypoplasia in 2.4%
• May be the best single ultrasound marker for second-trimester risk assessment when performed by experienced operators

Ethnic Variation

Proposed Screening Strategy (Two-Stage Approach)

• Risk ≥ 1:100 after NT + biochemistry → offer CVS directly
• Risk < 1:1000 → reassurance, no further testing
• Risk 1:101 to 1:1000 → perform NB assessment (applies to ~15% of pregnancies)

Clinical Management When Absent NB Is Found

• Isolated absent NB in first trimester (NT < 95th percentile): Low likelihood of chromosomal microarray (CMA) abnormality; not routinely an indication for invasive testing alone
• Isolated absent NB in euploid fetus without other second-trimester anomalies: Usually associated with good neonatal outcome
• Absent NB + increased NT or other markers: Significantly increases aneuploidy risk; discuss invasive diagnostic testing (CVS/amniocentesis) and/or cell-free DNA (cfDNA)
• Credentialed providers only: The NTQR and Fetal Medicine Foundation offer certification for NB assessment

Other Aneuploidies

Summary Points

1. Absent NB is a first- and second-trimester soft marker strongly associated with trisomy 21
2. It is assessed in the midsagittal plane at 45 degrees; the NB must be less echogenic than the overlying skin to call it absent
3. Sensitivity for trisomy 21: ~65-73% (first trimester), ~60% (second trimester); false-positive rate: <1%
4. Ethnic variation significantly alters the likelihood ratio - always adjust for race
5. Best used as a contingency marker in intermediate-risk patients, not universal first-tier screening
6. Isolated absent NB with normal NT and no other anomalies has a generally favorable prognosis
7. Combined screening (NT + biochemistry + NB) achieves ~93-97% DS detection

Hypoplastic Left Heart Syndrome (HLHS) in the Fetus

Definition

Anatomy and Subtypes

• Coarctation shelf present in 80% of patients
• Large ductus arteriosus; main pulmonary artery dilated
• Segmental pulmonary arteries are small (reduced intrauterine pulmonary blood flow)
• Left atrium typically smaller than normal; leftward displacement of septum primum
• Interatrial communication (foramen ovale) is nearly always present but is often restrictive

Pathophysiology

• All pulmonary, systemic, and coronary blood flow comes from the RV via the ductus
• Pulmonary venous return enters the left atrium but cannot cross the stenotic/atretic mitral valve → shunted right-to-left across the foramen ovale → volume loads the RV
• As pulmonary vascular resistance falls postnatally, RV output is preferentially directed to the lungs → systemic hypoperfusion + coronary ischemia
• Ductal closure = incompatible with life

Prenatal Diagnosis (Fetal Echocardiography)

Key Diagnostic Views

• Markedly abnormal 4CV at midgestation
• No inflow into the LV (no mitral valve / mitral atresia)
• Severely hypoplastic LV with intact ventricular septum (usually)
• The RV dominates the heart

• Aortic arch fills retrograde from the ductus arteriosus
• Color flow Doppler confirms pulsatile retrograde flow into the transverse arch

Critical Additional Assessment: The Foramen Ovale

• Restriction to left-to-right flow → pulmonary venous congestion → left atrial hypertension → dilated LA and pulmonary veins
• Can lead to irreversible pulmonary vascular disease
• May develop as late as the third trimester
• May not be confirmed by 2D alone; requires spectral and color flow Doppler ± pulmonary vein assessment
• Fetuses with restrictive/intact atrial septum may benefit from percutaneous enlargement of the foramen ovale during the second trimester to prevent pulmonary vascular disease

Progressive/Evolving HLHS

• Severe aortic stenosis present by 18-20 weeks may evolve into HLHS by term - the LV initially dilates (dilated cardiomyopathy pattern), then becomes hypoplastic
• Signs of evolving HLHS: dilated poorly functioning LV, endocardial fibroelastosis (bright LV endocardium), mitral regurgitation, L-to-R foramen ovale flow, retrograde transverse arch flow

Associated Abnormalities

• Increased risk for aneuploidy (chromosomal anomalies)
• Increased risk for central nervous system abnormalities (congenital or acquired)
• Associated VSD (if present, LV may retain relatively normal size due to R-to-L shunting)

Antenatal Management

Delivery Planning

• Deliver at a tertiary care center experienced with complex congenital heart defects
• Fetuses with HLHS + restrictive/intact foramen ovale: consider planned cesarean delivery to allow controlled environment for immediate neonatal intervention
• Prostaglandin E1 (PGE1) must be ready to initiate at delivery to maintain ductal patency

Fetal Intervention (Selected Cases)

• In 108 fetuses (2002-2018): >83% technically successful
• Biventricular circulation achieved in 33-38% of technically successful cases
• Overall intraprocedural complications: 48.1% (fetal bradycardia, pericardial effusion, pleural effusion, balloon rupture)
• Fetal death within 2 days: 16.7%
• Survival at 1 year: 80% ± 4%; at 5 years: 75% ± 5%

Postnatal Management: Three-Stage Palliation

Stage 1 - Norwood Procedure (within first week of life)

• Pulmonary root connected to native ascending aorta
• Hypoplastic arch augmented with homograft patch
• Pulmonary blood flow via either:
  • Modified Blalock-Taussig shunt (mBTS): innominate artery → right pulmonary artery
  • Sano shunt (RV-PA conduit): 5-6 mm Gore-tex graft directly from RV to PA
• Wide atrial septectomy to prevent pulmonary venous hypertension

• Transplantation-free survival at 12 months: Sano 74% vs. mBTS 64% (P = .01)
• Sano group had more unintended interventions and complications
• RV size/function at 14 months: similar between groups

Stage 2 - Glenn Procedure (~6 months)

• Bidirectional cavopulmonary anastomosis
• Superior vena cava connected to right pulmonary artery

Stage 3 - Fontan Procedure (~2-3 years)

• Inferior vena cava connected to pulmonary artery (total cavopulmonary connection)
• Separates pulmonary and systemic circuits

Prognosis and Outcomes

• With modern surgical management, Norwood survival exceeds 90% at experienced centers
• Outcomes for HLHS remain significantly worse than for other complex CHD
• Predictors of poor outcome:
  • Low birth weight
  • Significant tricuspid regurgitation
  • Restrictive interatrial communication
  • Poor RV function
  • Extracardiac or chromosomal anomalies
• Significant neurodevelopmental morbidity remains a concern (CNS injury from chronic hypoxemia + surgical insults)

Counselling Points for HLHS

1. What HLHS is - underdeveloped left heart, duct-dependent systemic circulation
2. Natural history without treatment - invariably fatal
3. Three management options:
   • Three-stage palliative surgery (Norwood → Glenn → Fontan)
   • Cardiac transplantation (limited by organ availability; 24% die waiting)
   • Comfort/palliative care only
4. Surgical risks and outcomes - >90% Norwood survival at expert centers, but lifetime morbidity remains
5. Neurodevelopmental concerns - higher rates of cognitive, motor, and behavioral difficulties
6. Risk of aneuploidy - offer chromosomal testing
7. Foramen ovale restriction - if present, worsens prognosis and changes delivery planning
8. Delivery planning - need for tertiary center, PGE1 readiness, possible cesarean for restrictive FO
9. Quality of life considerations - Fontan circulation is palliation, not cure; long-term Fontan complications (protein-losing enteropathy, arrhythmia, hepatic disease, lymphatic issues)
10. Recurrence risk - familial congenital heart defects