Handbook of Genetic Counseling/Trisomy 18

Trisomy 18

Contracting

• What do you know about why you have been referred?
• What do you know about the triple screen? What is your understanding of your test results?
• What questions or concerns would you like to address today?
• Overview of session:
  • Family and medical history
  • Explanation of maternal serum screening
  • Overview of results and what they mean
  • Explanation of genes and chromosomes
  • Information on Trisomy 18
  • Options for the future

Prenatal Intake

• Important to obtain information on pregnancy and family history to help assess potential risks to pregnancy
• Prenatal intake
  • How many times have you been pregnant? Any previous miscarriages or stillbirths?
  • History of infertility?
  • LMP beginning of November? EDC middle of August?
  • Any illness - infections, colds, fever, rashes?
  • Any bleeding?
  • Any exposures - X-rays (including dental), smoking, alcohol, recreational drugs, medications?
  • Any problems with pregnancy?
  • Personal background - occupation, religion, ethnicity, chronic illnesses for consultand and partner
  • Consanguinity?
• Family history
  • Review information obtained previously
  • Any history of miscarriages, infertility, stillbirths, birth defects?
  • Other chronic illnesses, learning problems, health problems that we did not discuss?

Maternal serum screening

• Background
  • Screening test
    • Not a diagnostic test
    • Used to identify women who are at increased risk for certain birth defects
      • These women then offered diagnostic testing
      • Negative or "normal" result does not mean that a child will not have a birth defect
      • Positive result is not a diagnosis of an abnormality
    • Can identify women at increased risk for Trisomy 21, Trisomy 18, or open neural tube defects
  • Blood test
    • Fetal and placental products can be detected in mother's blood serum during pregnancy
    • Can be offered from 14-22 weeks but most accurate at 16-18 weeks
• Indirect measure of levels of three substances in mother's blood
  • Alpha-fetoprotein (AFP)
    • Produced by liver of fetus and excreted into amniotic fluid
    • Passes into mother's bloodstream and concentration rises gradually throughout pregnancy
  • Human chorionic gonadotropin (HCG)
    • Pregnancy hormone made by the placenta
    • Level peaks at 10 weeks and declines throughout pregnancy
  • Unconjugated estriol (uE3)
    • Hormone made by fetus and placenta
    • Level increases throughout pregnancy

Risk assessment

• Laboratory calculates a woman's risks based on levels of three substance plus other factors
  • Gestational age
    • Marker levels change throughout pregnancy
    • Inaccurate dates are common reason for false positive
    • Gestational age can be confirmed by ultrasound
  • Maternal age
  • Multiple gestations
  • Maternal weight
    • Increased weight means increased blood volume
    • Markers will be diluted in serum and their concentration lower
  • Maternal race
  • Diabetic status
    • Insulin-dependent diabetics have increased risk for neural tube defects
    • Tend to have lower AFP levels, so use lower AFP cutoff
• Your specific results:
  • Every pregnancy has 3-5% risk for congenital malformation
    • Background risk
    • Most of these problems cannot be detected prenatally
  • As a woman's age increases, her risk for certain birth defects increases
  • Risk figures for your pregnancy:
    • ONTD: ________
    • Down Syndrome: ________ compared to age associated risk _______
    • Trisomy 18: ________ compared to age associated risk _______
  • Screen positive for increased risk for Trisomy 18
    • Occurs when AFP, hCG, and uE3 levels are all lower than expected
    • Evaluation of screening performance
      • Up to 100 of every 1,000 women who take test will have abnormal result (up to 10%)
        • Only 3 of those 100 women will have a baby with a birth defect
        • Most abnormal test results indicate dates are wrong or another factor above has not been accurately accounted for
        • Important to remember that test cannot identify all birth defects
      • Abnormal result could be normal variation
      • Sometimes no explanation for abnormal results - increased risk for 3rd trimester complications
      • Test can detect:
        • 60% of Trisomy 18
        • 80% of ONTD
        • 60% Down Syndrome

Trisomy 18

• Clinical picture
  • Can cause heart problems, kidney problems and other health issues
  • Usually fatal within first year of life
  • Children that survive have severe intellectual disability
• Increased risk for pregnancy loss

Options for further testing

• Ultrasound
  • Confirm gestational age or identify multiple fetuses to help interpret triple screen results
  • Can detect many major birth defects - rule out 95% of NTDs if visualization is not limited
  • Many fetuses with Trisomy 18 have certain "markers" that can be identified on ultrasound
    • Growth retardation
    • Single umbilical artery
    • Heart problems
    • Polyhydramnios
  • Can't diagnose chromosomal abnormalities
• Amniocentesis
  • Performed after 15 weeks
  • Diagnostic test for some conditions
    • 99.7% accuracy for fetal chromosome analysis
    • Detects 96% of open neural tube defects by testing AFAFP
    • Cannot detect all birth defects or mental retardation
  • Risk of pregnancy loss due to procedure is 0.5%
  • Explain amniocentesis if interested
    • Insert needle into abdomen through uterus to take sample of amniotic fluid that contains cells from fetus used for karyotyping
    • Procedure:
      • Ultrasound to locate fetus and placenta
      • Abdomen cleaned with betadeine and local anesthetic (xylocaine) used to numb outer layer of skin
      • Physician inserts needle in abdomen through uterus under ultrasound guidance
        • Needle inserted 1-2 minutes
        • May feel some discomfort similar to menstrual cramp
      • Fluid is sent to lab and results ready in 1-2 weeks
    • Recommendations
      • No strenuous activity for 24 hours
      • Notify doctor if severe cramping, bleeding or leakage of fluid because there is very small risk of infection
      • Rh negative mothers should take RhoGAM

Potential Psychosocial Issues

• Emphasize the importance of choice
• Religious beliefs impact decisions about testing and termination
• Anger, distrust because of family physicians advice
• Anxiety, sadness, disbelief, fear concerning possibility of Trisomy 21
  • Provide reassurance when possible
  • Explain benefits of prenatal diagnosis to help prepare emotionally, mentally, and socially for birth of child with chromosome abnormality
• False positive may cause unnecessary anxiety

Support Groups

Trisomy 18 Foundation at www.trisomy18.org

References

• Creasy RK, and Resnik R, eds. (1994) Maternal-Fetal Medicine 62-84.
• "Maternal Blood Screening." (2001) March of Dimes Fact Sheet. http://www.modimes.org.
• Gardner RJM, and Sutherland GR. (1996) Chromosome Abnormalities and Genetic Counseling 325-371.
• Milunsky A, ed. (1998) Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment 179-23**

Notes

The information in this outline was last updated in 2002.