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

Genes and Chromosomes

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.