Quad Screen

1. Indication
   1. Congenital defect screening in low risk pregnancy
2. Tests comprising Quad Screen
   1. Alpha-fetoprotein (AFP)
      1. Increased with Neural Tube Defects
      2. Decreased in Trisomy 21 and Trisomy 18
   2. Human chorionic gonadotropin (Free bHCG)
      1. Increased in Trisomy 21 and decreased in Trisomy 18
   3. Unconjugated Estriol (uE3)
      1. Decreased in Trisomy 21 and Trisomy 18
   4. Inhibin A
      1. Increased in Trisomy 21 and normal in Trisomy 18
3. Precautions
   1. Does not replace Amniocentesis if age 35 years or older
   2. Trisomy 21 risk increases based on Multiple Pregnancy
      1. Singleton gestation: Age 35 years
      2. Twin Gestation: Age 33 years
4. Protocol
   1. Counsel patient before screening
      1. Screening for Neural Tube Defects and Trisomy 21, 18
      2. Protocol if screening positive and diagnostic risks
      3. Accuracy and limitations of tests
   2. Timing of Quad Screen
      1. Optimal time: 16 to 18 weeks gestation
      2. Range of testing: 15 to 22 weeks gestation
      3. Shifting to first trimester is being investigated
   3. Interpretation of abnormal results
      1. Chromosomal abnormalities suggested
         1. Findings
            1. Trisomy 21: AFP, uE3 low, hCG,Inhibin high
            2. Trisomy 18: AFP, hCG and uE3 decreased
         2. Perform Amniocentesis for chromosomal analysis
      2. Neural Tube Defects suggested (AFP increased)
         1. Ultrasound to confirm gestational age
         2. Recalculate AFP based on Ultrasound gestational age
            1. Redraw Triple Screen if first test <15 weeks
         3. Perform diagnostics if AFP still elevated
            1. Repeat AFP level
            2. Level II Ultrasound Fetal Survey
            3. Consider Amniocentesis
               1. Amnion AFP level
               2. Amnion acetylcholinesterase level
5. New Protocols: First trimester screening
   1. First trimester screening for trisomy 18 and Trisomy 21
      1. Maternal age
      2. Free Beta human chorionic gonadotropin (bHCG)
      3. Pregnancy associated plasma protein A
      4. Fetal Ultrasound
         1. Nuchal Translucency
            1. Test Sensitivity: 77%
            2. High false positive rate: >4%
         2. Nasal bone absent
            1. Test Sensitivity: 70%
            2. False positive rate: 1.5%
   2. Efficacy of 4 factors in predicting trisomy 18 or 21
      1. As accurate as second trimester screening
   3. References
      1. Wapner (2003) N Engl J Med 349:1405-13
6. Quad Screen results predict pregnancy outcomes
   1. Unexplained abnormal tests confer 2 or more fold risk
   2. Unexplained increased AFP confers poor outcome risk
      1. Preeclampsia:
      2. Intrauterine Growth Retardation
      3. Intrauterine Fetal Demise
      4. Preterm Labor
      5. Low birth weight
      6. Placental Abruption
      7. Perinatal death
   3. Unexplained increased hcg confers poor outcome risk
      1. Preeclampsia
      2. Preterm Labor
      3. Low birth weight infant
      4. Intrauterine Fetal Demise
   4. Unexplained decreased estriol confers poor outcome risk
      1. Associated with specific Genetic Syndromes
   5. References
      1. Dugoff (2005) Obstet Gynecol 106:260-7
7. References
   1. Graves (2002) Am Fam Physician 65(5):915-22