What are the risks of fetal demise for trisomy 18 (Edwards syndrome)?

Risks of Fetal Demise in Trisomy 18 (Edwards Syndrome)

Trisomy 18 has an extremely high rate of fetal demise, with approximately 70% of fetuses alive in the second trimester being spontaneously lost before term. 1

Intrauterine Fetal Demise Patterns

• The risk of fetal demise in trisomy 18 is significantly higher than in the general population and other common chromosomal abnormalities:

  • Overall intrauterine fetal death (IUFD) rate: 32-50% of prenatally diagnosed cases 2, 3
  • Mean gestational age at fetal demise: 32-35 weeks 2, 4
  • No specific clustering pattern for timing of losses after 24 weeks - demise occurs uniformly throughout the third trimester 4

• In a perinatal center study, among 58 prenatally diagnosed cases 2:

  • 27.6% experienced IUFD between 28-41 weeks (mean 34.6 weeks)
  • 17.2% died during labor (30-40 weeks)
  • Total fetal demise rate: 44.8% with mean gestational age of 35 weeks

Risk Factors and Patterns

• Female fetuses with trisomy 18 have higher survival rates than males 2
• Preterm birth is significantly more common (34.8%) compared to general population 2
• Congenital heart defects, present in most trisomy 18 fetuses, contribute significantly to mortality 3, 5
• Multiple structural anomalies increase the risk of fetal demise 6

Comparison to Other Chromosomal Abnormalities

• Trisomy 18 has a higher rate of fetal demise (32.1%) compared to trisomy 21 (10.2%) 4
• Trisomy 18 losses tend to occur later in pregnancy compared to trisomy 21:
  • Only 14.8% of trisomy 18 losses occur before viability (24 weeks)
  • 37.1% of trisomy 21 losses occur before viability 4

Prenatal Detection and Monitoring

• Early detection through combined screening methods is possible:

  • First trimester screening using maternal age, nuchal translucency, fetal heart rate, and maternal serum markers 6, 7
  • Non-invasive prenatal screening (NIPS) has high detection rates (98.83%) with low false-positive rates (0.07%) 6
  • Diagnostic confirmation through amniocentesis or CVS is recommended when screening is positive 6

• Ultrasound markers that may indicate increased risk:

  • Choroid plexus cysts (present in 30-50% of trisomy 18 fetuses) 1, 6
  • Structural heart defects
  • Clenched hands with overlapping fingers
  • Club foot (talipes)
  • Growth restriction
  • Polyhydramnios 6

Clinical Implications

• The high rate of fetal demise has implications for prenatal counseling and management decisions
• The risk of unnecessary maternal morbidity from cesarean sections in undiagnosed cases is significant 1
• For those who continue pregnancy after diagnosis, understanding the high likelihood of fetal demise is important for expectation management
• The high mortality rate continues after birth, with median survival of only 18 days in live-born infants 3

Caveats and Pitfalls

• Be cautious about isolated soft markers (like choroid plexus cysts) without other findings, as they have limited predictive value when found alone 1, 6
• Detection rates vary by gestational age - early ultrasound (11-14 weeks) has lower sensitivity (50%) compared to 18-22 week scans (75%) 6
• The true detection rate for trisomy 18 is difficult to reliably quantify due to the high fetal loss rate from late first trimester to term 1