Prenatal diagnosis of congenital defects

Prenatal diagnosis of congenital defects

Prenatal diagnosis of congenital defects

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Prenatal Screening - The First Look

  • First Trimester (11-13+6 wks): Combined test is standard.
    • Biochemical: ↑ free β-hCG, ↓ PAPP-A.
    • USG: ↑ Nuchal Translucency (NT).
  • Second Trimester (15-20 wks): Quadruple test.
    • Markers: ↓ AFP, ↑ β-hCG, ↓ uE3, ↑ Inhibin A.
  • NIPS/NIPT: Non-invasive prenatal screening/testing. Highest detection rate for aneuploidies.

⭐ In Down Syndrome, all markers in the second-trimester screen are down except for hCG and Inhibin A, which are high.

Fetal Nuchal Translucency (NT) Ultrasound Measurement

1st Trimester Screening - The Early Birds

  • When: 11-14 weeks gestation (or CRL 45-84 mm).
  • What: A combined screening test for aneuploidies (Trisomy 21, 18, 13).
  • Components:
    • Biochemical Markers (Double Marker Test):
      • ↓ PAPP-A (Pregnancy-Associated Plasma Protein-A)
      • ↑ Free β-hCG (human chorionic gonadotropin)
    • Sonographic Markers (NT Scan):
      • ↑ Nuchal Translucency (NT)
      • Absent/Hypoplastic Nasal Bone

Fetal Ultrasound: Nuchal Translucency Measurement

⭐ The combined test boasts a detection rate of ~85% for Down Syndrome. It is a screening test; positive results require diagnostic confirmation (e.g., CVS or amniocentesis).

2nd Trimester Screening - The Mid-Game Scan

  • Timing: 15-20 weeks (ideal: 16-18 weeks).
  • Tests: Ultrasound (for anomalies) + Maternal serum screening.
  • Quadruple Test: Measures 4 markers:
    • Alpha-fetoprotein (AFP)
    • Human chorionic gonadotropin (hCG)
    • Unconjugated estriol (uE3)
    • Inhibin A

Fetal ultrasound images for prenatal anomaly detection

⭐ The Quadruple test has a detection rate of approximately 80% for Down syndrome.

Invasive Diagnostic Tests - The Decisive Divers

  • Definitive diagnosis for chromosomal/genetic disorders. Involves sampling fetal tissue/fluid, each with specific timing and risks.
TestGestational Age (GA)Risk of Fetal LossKey Points
Chorionic Villus Sampling (CVS)10-13 wks~1%Earliest test. Cannot detect NTDs.
Amniocentesis15-20 wks~0.5%Can detect NTDs (↑AFP).
Cordocentesis (PUBS)>18 wks1-2%Rapid karyotype; fetal therapy.

NIPT & Beyond - The DNA Detective

  • Non-Invasive Prenatal Testing (NIPT): Analyzes cell-free fetal DNA (cffDNA) from maternal plasma.
    • Performed from 10 weeks gestation onwards.
    • Screens for common aneuploidies (Trisomy 21, 18, 13) & sex chromosome abnormalities.
    • High detection rate for Down syndrome (>99%).
  • Confirmatory Tests: NIPT is a screening tool; positive results require confirmation via Chorionic Villus Sampling (CVS) or Amniocentesis.

Fetal Fraction: The proportion of cffDNA in maternal blood. A level <4% is a major cause of NIPT failure or false-negative results.

High‑Yield Points - ⚡ Biggest Takeaways

  • Nuchal Translucency (NT) is the most important first-trimester ultrasound marker for Down syndrome.
  • The double marker test (PAPP-A, β-hCG) is the key first-trimester biochemical screen.
  • The quadruple screen (AFP, hCG, estriol, inhibin A) is the standard second-trimester biochemical test.
  • Amniocentesis (15-20 weeks) and Chorionic Villus Sampling (CVS) (10-13 weeks) are the primary invasive diagnostic tests.
  • Cell-free fetal DNA (cffDNA) is the most sensitive non-invasive screening test for aneuploidy.

Practice Questions: Prenatal diagnosis of congenital defects

Test your understanding with these related questions

A 40-year-old woman in her 18th week of pregnancy based on the last menstrual period (LMP) presents to her obstetrician for an antenatal check-up. The antenatal testing is normal, except the quadruple screen results which are given below: Maternal serum alpha-fetoprotein (MS-AFP) low Unconjugated estriol low Human chorionic gonadotropin (hCG) high Inhibin-A high Which of the following conditions is the most likely the cause of the abnormal quadruple screen?

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Flashcards: Prenatal diagnosis of congenital defects

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Why is screening for phenylketonuria performed 2-3 days after birth? _____

TAP TO REVEAL ANSWER

Why is screening for phenylketonuria performed 2-3 days after birth? _____

May be normal at birth due to maternal enzymes

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