SCREENING FOR CONGENITAL ABNORMALITIES

I. Screening for Trisomy 21 (Down's syndrome) and Neural Tube Defects

  1. First trimester ultrasound screening
    1. Fetal nuchal translucency
      1. May indicate edema due to cardiac abnormalities, which are common in chromosomal abnormalities
      2. At 10-14wks gestation, indicates subcutaneous edema in the fetal neck; may predict Down Syndrome (trisomy 21) with similar sensitivity/specificity to serum screening (Lancet 352:343, 1998--JW)
      3. In a study in 38,033 women > 16yo with singleton pregnancies who underwent first-trimester screening (ultrasound assessment of fetal nuchal translucency, measurement of pregnancy-associated plasma protein A, and free beta-hCG) and 2nd-trimester quadruple screening, at a 5% false-positive rate, sensitivity of first-trimester screening at 11wks was 87% and of 2nd-trimester screening was 81%; doing both had sensitivity of 96% (NEJM 353:2001, 2005--JW)
    2. 1st trimester maternal serum screening
      1. Free beta-hCG
      2. Pregnancy-associated plasma protein A ("PAPP-A")
    3. Combination of u/s for fetal nuchal translucency and maternal serum screening
      1. In a prospective study in 38,033 women > 16yo with singleton pregnancies who underwent first-trimester screening with (u/s for fetal nuchal translucency + free beta-hCG + PAPP-A) and 2nd-trimester screening with maternal serum "quadruple screen," at a false-positive detection rate of 5%, first-trimester screening had sensitivity of 85% for trisomy 21 and 2nd-trimester screening had sensitivity of 81%.  The two together had sensitivity of 95%.  First-trimester screening had highest sensitivity at 11wks (NEJM 353:2001, 2005--JW)
      2. Can also identify other chromosomal abnormalities (e.g. trisomy 13 or 18, Turner syndrome, triploidy, or deletions) (Am. J. Obs. Gyn. 192:1761, 2005--JW)
    4. Absence of nasal bones
      1. Had sensitivity of 62.1% and specificity of 99.4% for trisomy 21 when done at 11-13wks gestation in one retrospective study (Am. J. Obs. Gyn. 195:109, 2006--JW)
  1. Maternal Serum screening in early 2nd trimester
    1. "Triple Screen" = AFP, hCG, Estriol
      1. AFP is typically reduced in Down's sd. in early 2nd TM (high in neural tube defects)
      2. Mat. serum hCG (twice as high with Down Sd.)
      3. Unconjugated estriol (25% lower with Down Sd.)
      4. Note that elevated alpha-fetoprotein level may also be seen in placenta accreta
    2. Also, "Quadruple screen" = Triple Screen + Inhibin A; may increase sensitivity for Down's w/o decreasing specificity

II. Screening for Down Syndrome and other genetic conditions by obtaining fetal material for cytology and/or DNA analysis

  1. Amniocentesis
  2. Chorionic villus sampling
  3. Collection of fetal trophoblast cells from maternal  blood or endocervical mucus--Investigational as of 2005

III. ACOG recommendations 2007 (Obs. Gyn. 109:217, 2007--JW)

  1. Use of both biochemical markers and nuchal translucency measurement is more effective than nuchal translucency measurement alone at detecting Down syndrome
  2. If first trimester screening is positive offer genetic counseling and either chorionic villus sampling or 2nd-trimester amniocentesis
  3. Even if do first-trimester testing, still important to do 2nd-trimester screening for neural tube defects.