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A. Risk in Pregnancy [3] navigator

  1. Overall fetal loss rate ~4-5/1000
  2. Subgroup analysis indicates that most of these losses occur in specific populations
  3. Common Birth Defects
    1. About 2% of all prenancies result in child with major malformation / genetic disease
    2. Congenital Heart Defects are most common
    3. Neural Tube Defects ~1-2/1000 births
    4. Chromosomal Abnormality ~0.5%
    5. Down Syndrome - 1/800 births (overall rate; rates are age dependent)
    6. Fragile X Syndrome - 1/1500 males and 1/2500 females (mental retardation)
  4. Populations at High Risk for Fetal Loss or Still Birth or Fetal Abnormality
    1. Diabetes - babies tend to be large with relatively immature lungs
    2. Chronic Hypertension
    3. Preeclampsia - (and other stresses) fetus tends to have relatively mature lungs but fetus is often delivered earlier due to maternal disease
    4. Medications - anti-epileptics (eg. valproic acid), methotrexate, retinoids, others
    5. Intrauterine Growth Retardation (IUGR)
    6. Maternal age >35 years
    7. Anticardiolipin Antibody: Fetal Loss relative risk ~3.5X increase with positive IgG Ab
    8. Other Medical Problems: hypothyroidism, systemic lupus, thrombocytopenia, etc.
  5. Newborns are now screened for a variety of genetic diseases
  6. Screened for Specific Infectious Diseases ("TORCHS" Series):
    1. Toxoplasmosis
    2. Other: pelvic inflammatory disease, bacterial vaginosis
    3. Rubella
    4. Cytomegalovirus (CMV)
    5. Herpesviruses and HIV
    6. Syphilis

B. Routine Prenatal Screening and Diagnostic Testing [1,3]navigator

  1. Indications
    1. Previous pregnancy affected by aneuploidy
    2. Late maternal age
    3. High risk ethnic groups: for example, Tay-Sachs, Sickle Cell Anemia, Thalassemia, others
  2. Timing of Fetal Testing
    1. To determine when to deliver baby
    2. That is, when stresses become too high
  3. Fetal Testing and appropriate followup obstetric care decrease fetal loss rate to ~1/1000

C. Prenatal and Fetal Testsnavigator

  1. Fetal Ultrasound
    1. Alone
    2. with Non-Stress Test (NST)
    3. with Biophysical Profile (BioP)
    4. Contraction Stress Test (CST)
  2. Maternal Serum Screening
  3. Invasive Testing (see below)
    1. Amniocentesis
    2. Chorionic Villus Sampling
  4. Fetal DNA can be found in maternal circulation, which may permit simple testing [5]

D. Non-Stress Test (NST)navigator

  1. Measures acceleration of heart rate coupled with fetal motion
  2. Normal fetuses have >15bpm increase in HR for 15 seconds > baseline coupled with motion
  3. In addition, must have 2 accelerations within 20 minutes
  4. If criteria are fulfilled, then test is said to be "Reactive"
  5. A Reactive NST is highly predictive for fetal viability for >72 hours after the test
  6. If NST is non-reactive
    1. Then BOP is usually performed
    2. In some cases (usually of maternal and/or fetal compromise), delivery will be induced
    3. Recall that fetal lung maturation is enhanced in certain kinds of stress

E. Biophysical Profile (BOP)navigator

  1. Usually performed in cases of non-reactive NST
  2. Scoring is 10 points, with two points for each part
    1. NST
    2. Amniotic Fluid Index (AFI): <5 = oligohydramnios; >25 = polyhydramnios
    3. Fetal Tone (usually seen with good movement) - body movements
    4. Fetal Motion (2 full flexion/extension movements in 20 minutes) - extremity movements
    5. Fetal Breathing (30 seconds of fetal breathing)
  3. If BOP is poor (usually 4-6), then Provocative Stress Test may be performed

F. Contraction (Provocative) Stress Testnavigator

  1. Provocations
    1. Nipple stimulation (2 min on, 2 min off) - leads to natural oxytocin release
    2. Oxytocin challenge test (OCT) - give oxytocin iv causing uterine contractions
    3. Good test requires 3 or more contractions, 30 seconds each within a 10 min period are required
  2. Measure acceleration or deceleration of fetal heart rate with contractions
    1. Contractions will usually decrease blood flow to the placenta
    2. In normal situations, this decrease will not affect fetal oxygenation
    3. In stressed/abnormal cases, the decrease leads to fetal hypoxia and relative bradycardia (also called late decelerations)
  3. Positive test is abnormal and implies that decelerations occurred
  4. Ultrasonography is usually performed during the test
    1. A reactive baby during the non-provoked periods is said to have a Reactive NST
    2. Thus, a Negative CST with Reactivity is the best possible outcome
  5. Failure in these tests may result in induction of delivery

G. Maternal Serum Profiles [1,3] navigator

  1. Main goal is early detection of Down Syndrome (Trisomy 21)
    1. Various maternal serum analytes are outside of normal range with Down Syndrome fetus
    2. Maternal blood contains fetal DNA which may eventually permit simple direct testing [5]
    3. At present time, ~2.5 million pregnant women undergo testing each year
    4. Recommended test now includes four analytes: AFP, HCG, unconjugated estriol, inhibin [10]
    5. Current tests are usually performed in the second trimester (17-19 weeks)
    6. Quadruple test sensitivity 75-80% and 7% false positives [10]
  2. alpha-Fetoprotein (AFP)
    1. Maternal serum levels of AFP elevated in a number of conditions
    2. Most prominently elevated in multiple neural tube (closure) defects
    3. Reduced levels found in Trisomy 18 (Edward Syndrome) and Trisomy 21 (Down Syndrome)
    4. Reduced levels also in hydatidiform mole, fetal demise, increased maternal weight
    5. Detects vast majority of neural tube defects and some cases of trisomy 21
  3. Causes of Elevated Maternal Serum AFP (Table 1 in Ref [1])
    1. Gestational age younger than calculated - most common reason
    2. Spina Bifida
    3. Anencephaly
    4. Congenital skin defects: pilonidal cyst, abdominal wall defects
    5. Gastrointestinal defects: obstruction, liver necrosis, cloacal exstrophy
    6. Cystic hygroma
    7. Sacrococcygeal teratoma
    8. Renal anomalies: urinary obstruction, polycycstic kidney, congenital nephrosis, absent kidney
    9. Osteogenesis imperfecta
    10. Low birth weight
    11. Oligohydramnios
    12. Multiple gestation
    13. Decreased maternal weight
  4. HCG
    1. Total HCG or it's free ß-subunit can be used in most cases
    2. Elevated in Trisomy 21 (Down Syndrome)
    3. Reduced levels found in Trisomy 18
  5. Unconjugated Estriol
    1. Produced by placeta from precursors in fetal adrenal gland and liver
    2. Increases throughout pregnancy to higher level than normal ovarian production
    3. Levels reduced in Trisomy 18 and 21
    4. Estriol testing increases detection of trisomy 21 in women younger than 35 years
  6. Dimeric Inhibin A [2]
    1. A 2X elevation found in Down Syndrome
    2. Normal ranges are detected in Trisomy 18
  7. First Trimester Down Syndrome and Trisomy 21 Testing [11]
    1. Maternal ß-human chorionic gonadotropin (HCG) and pregnancy associated plasma protein A (PAPA) are key
    2. Age. maternal levels free ß-HCG, and PAPA in 35 year olds identified 90% of trisomy 21 with 15.2% false positive rate, and 100% of trisomy 18
  8. Second Trimester Down Syndrome Testing
    1. AFP, HCG and estriol (Triple Screen) optimally tested between 16-18 weeks gestation
    2. Can be useful when done from 15-22 weeks gestation
    3. Cannot completely replace amniocentesis or chorionic villous sampling
    4. Sensitivity of Down Syndrome detection ~60% with 95% specificity with these 3 tests
    5. Adding dimeric inhibin A to first three tests increases detection to ~75% [2]
    6. Combining inhibitin A with Triple Screen is probably best second trimester test
    7. Optimal detection of Down Syndrome may involve first and second trimester testing including PAPA, HCG and AFP [9]
    8. Ultrasound measurement of nuchal translucency requires specialized interpretation [7]
    9. Combination of HCG and PAPA in first trimester detects ~60% of Down Syndrome with 95% specificity [7]
  9. Triple Screen Interpretation [1]
    1. Suspect Neural Tube Defects: AFP increased, HCG and estriol normal
    2. Suspect Trisomy 21: AFP and estriol decreased, HCG increased
    3. Suspect Trisomy 18: AFP, HCG, estriol decreased

H. Amniocentesis [1,3,4]navigator

  1. Performed midtrimester (15-20 weeks gestation)
  2. Estimated risk of fetal loss 0.5-1.0%; positive predictive value >90%
  3. Relative Indications
    1. Maternal age >34 years
    2. History of fetus or infant with aneuploidy
    3. Women with known chromosomal abnormality(s)
    4. High risk for known genetic diseases - eg. Tay-Sachs, Sickle Cell, etc.
    5. Abnormal maternal serum profiles
    6. Ultrasound evidence of anomaly
  4. Early amniocentesis, done weeks 11-14, is investigational but appears to increase risk of fetal loss and talipes equinovarus [6]
  5. PCR analysis of amniotic cells can detect trisomy 21 in >99% of cases [8]

I. Chorionic Villus Sampling (CVS) [1,2,4]navigator

  1. Reliable technique for first trimester prenatal diagnosis (10-12 weeks gestation)
  2. Fetal loss risk is very close to that for amniocentesis and may be decreasing
  3. Ability to detect most diseases is similar to that for amniocentesis
  4. Major advantage is earlier use, but positive predictve value is about 50%

Resources navigator

calcApgar Score

References navigator

  1. Graves JC, Miller KE, Sellers AD. 2002. Am Fam Phys. 65(6):915
  2. Aitken DA, Wallace EM, Crossley JA, et al. 1996. NEJM. 334(19):1231 abstract
  3. Mennuti M. 1996. JAMA. 275(18):1440 abstract
  4. Stranc LC, Evans JA, Hamerton JL. 1997. Lancet. 349:711 abstract
  5. Dennis YM, Corbetta N, Chamberlain PF, et al. 1997. Lancet. 350:485 abstract
  6. Canadian Early and Mid-Trimester Amniocentesis Trial Group. 1998. Lancet. 351(9098):242 abstract
  7. Haddow JE, Palomaki GE, Knight GJ, et al. 1998. NEJM. 338(14):955 abstract
  8. Verma L, Macdonald F, Leedham P, et al. 1998. Lancet. 352(9121):9 abstract
  9. Wald NJ, Watt HC, Hackshaw AK. 1999. NEJM. 341(7):461 abstract
  10. Wald NJ, Huttly WJ, Hackshaw AK. 2003. Lancet. 361(9360):835 abstract
  11. Wapner R, Thom E, Simpson JL, et al. 2003. NEJM. 349(15):1405 abstract