Triple Screen and Quadruple Screen

PART 1: ANTENATAL SCREENING FOR DOWN SYNDROME

1. Introduction

• Goal: To identify pregnancies at "High Risk" (>1:250) for Trisomy 21, warranting invasive diagnostic testing (Amniocentesis/CVS).
• Strategy: Multimodal approach using Ultrasound markers and Maternal Serum Biochemistry.

2. First Trimester Screening (11 – 13+6 Weeks)

The Combined Test (Gold Standard for 1st Trimester)

• Components:
  1. Ultrasound: Nuchal Translucency (NT) measurement.
  2. Biochemistry: Maternal serum Free $\beta$-hCG + PAPP-A (Pregnancy Associated Plasma Protein-A).
• Down Syndrome Pattern:
  • NT: Increased (>95th percentile or >3mm).
  • Free $\beta$-hCG: Increased (~2.0 MoM).
  • PAPP-A: Decreased (~0.4 MoM).
• Sensitivity: 87–90% (False positive rate 5%).
• Additional USG Markers: Absence of Nasal Bone, Tricuspid Regurgitation, abnormal Ductus Venosus flow (improves detection to 95%).

3. Second Trimester Screening (15 – 20 Weeks)

Indicated for women presenting late or where NT scan was not available.

A. Triple Test

• Analytes: AFP + uE3 (Unconjugated Estriol) + hCG.
• Down Syndrome Pattern:
  • AFP: Low (~0.7 MoM).
  • uE3: Low (~0.7 MoM).
  • hCG: High (~2.0 MoM).
• Sensitivity: 60–70%.

B. Quadruple (Quad) Test

• Analytes: Triple Test components + Inhibin A.
• Down Syndrome Pattern: High Inhibin A (~1.8 MoM) + Pattern of Triple test.
• Sensitivity: 80% (Preferred over Triple test).

4. Cell-Free Fetal DNA (NIPS/NIPT)

• Technique: Analysis of cffDNA in maternal blood (from 10 weeks).
• Performance: >99% detection rate for Down Syndrome; False positive <0.1%.
• Role: Screening test (not diagnostic). High-risk results require confirmation via Karyotype.

PART 2: UTILITY OF TESTS IN OTHER DISORDERS

Beyond Down Syndrome, these screening modalities detect other chromosomal, structural, and metabolic anomalies.

1. Utility of The Combined Test (1st Trimester)

2. Utility of Triple & Quadruple Tests (2nd Trimester)

A. Neural Tube Defects (NTDs)

• Marker: Alpha-Fetoprotein (AFP).
• Pattern: Significantly Raised (>2.5 MoM).
• Conditions: Anencephaly (highest levels), Open Spina Bifida, Encephalocele.
• Note: Combined with Acetylcholinesterase (AChE) in amniotic fluid for diagnosis.

B. Abdominal Wall Defects

• Marker: Raised AFP.
• Conditions: Omphalocele, Gastroschisis.

C. Trisomy 18 (Edwards Syndrome)

• Pattern: "All markers are Low".
  • AFP: Low
  • uE3: Low
  • hCG: Low
  • Inhibin A: Normal/Low.

D. Smith-Lemli-Opitz Syndrome (SLOS)

• Defect: Defect in cholesterol synthesis (7-dehydrocholesterol reductase).
• Pattern: Very Low uE3 (Estriol requires fetal adrenal precursors derived from cholesterol).

E. Steroid Sulfatase Deficiency (X-Linked Ichthyosis)

• Pattern: Undetectable uE3.

F. Adverse Obstetric Outcomes

• Unexplained High AFP: Risk of placental abruption, IUGR, fetal death, or oligohydramnios.
• High Inhibin A: Associated with increased risk of Preeclampsia.

Summary Table of Patterns