Handbook of Genetic Counseling/Advanced Maternal Age - Chorionic Villus Sampling (CVS)-2

Advanced Maternal Age - Chorionic Villus Sampling (CVS)

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Maternal Age Associated Pregnancy Risks

Women over age of 35 considered at "high risk" for chromosomal abnormalities
Explain chromosomes and nondisjunction
Common trisomies associated with advanced maternal age
- Trisomy 21 (Down Syndrome)
  - Caused by presence of 3 copies of chromosome 21
  - Can result in characteristic facies, mild to moderate mental retardation, congenital heart disease and other health problems
  - Varying range of severity
  - Many children can go to school, adults may hold jobs and live semi-independently
- Trisomy 13 (Patau Syndrome) and Trisomy 18 (Edward Syndrome)
  - Caused by presence of 3 copies of chromosome 13 or 18
  - More severe medical issues than those associated with Down Syndrome
  - Usually fatal within first year of life
- Klinefelter Syndrome (47,XXY)
  - Caused by presence of an extra X chromosome
  - Phenotypic males who may have small testes and androgen deficiency
  - IQ may be 10-15 points lower than average

Testing Options

Triple marker screening
- Blood test performed at 15-22 weeks gestation
- Screening test, not diagnostic
  - In whole population, detects 62% of problems
  - False positive rate of 3.6%
- Indirect measurement of AFP, hCG, and uE3 production
- Detects some chromosomal abnormalities associate with maternal age
  - Down Syndrome (70% in women older than 35)
  - Trisomy 18 (60%)
  - Open neural tube defects (80-90%)
  - Does not detect all chromosomal abnormalities associated with maternal age
- Amniocentesis may be offered to follow-up on results
Ultrasound
- Capable of detecting many major birth defects
  - May identify ultrasound anomaly that could indicate a chromosomal abnormality
  - Cannot diagnose chromosome abnormality based on ultrasound findings
- Amniocentesis or CVS may be offered to follow-up on results
Chorionic Villus Sampling (CVS)
- Sample of placental tissue (chorionic villi) obtained
  - Tissue is from same embryonic origin as fetus
  - Should have same genetic composition as fetus
- Usually performed at 10-12 weeks gestation
- Technique
  - Transcervical
    - Begin with ultrasound exam to confirm fetal heart activity, appropriate growth, and location of placenta, uterus, and cervix
    - Patient placed in lithotomy position
    - Vagina and cervix cleaned with betadeine
    - Speculum is inserted and some physicians apply a tenaculum to the lip of the cervix to help manipulate the uterus
    - Catheter with a stylet inserted is guided into the placenta using US
    - Stylet removed and syringe inserted
    - Suction is applied to aspirate villi
    - May be slightly uncomfortable
  - Transabdominal
    - Begin with ultrasound exam
    - Abdomen cleaned with betadeine and xylocaine injection given to numb skin
    - Spinal needle with stylet guided through abdominal and uterine walls into placenta using ultrasound guidance
    - Stylet removed and syringe attached
    - Suction applied by syringe plunger and needlemoved back and forth
    - Can be performed at any time during pregnancy
    - May be moderately uncomfortable
  - Transcervical vs. transabdominal
    - Bleeding more common following transcervical (10%)
    - Cramping more common following transabdominal
    - No significant difference in risk for fetal loss
    - Some reports indicate transcervical may have higher risk for infection
  - Recommendations for medical care
    - Rh negative women should be given Rhogam
    - No exercise or strenuous activity for 24 hours
    - No sexual intercourse, douching, tub baths, or use of tampons for 72 hours
    - Notify OB if any of the following signs
      - Fever above 1000F
      - Heavy bleeding or cramping
      - Amniotic fluid leakage
    - Follow up ultrasound in a few days
    - MSAFP at 16-18 weeks
    - Ultrasound at 20 weeks to check fetal anatomy
- Risks/Benefits of CVS
  - 98-99% accuracy for fetal chromosome analysis
    - Allow identification of affected fetus early in pregnancy
    - Maternal cell contamination risk if 46,XX result
    - 1-2% chance for mosaicism
      - Presence of two or more cell lines that differ in chromosome composition
      - Difficult to interpret because may arise in vitro in lab, may be confined to placenta and not affect fetus, or may represent true fetal mosaicism
  - Can perform molecular DNA analysis or biochemical analysis if at risk fetus
  - Can't detect open neural tube defects
  - Can't detect all birth defects or mental retardation
  - Risk of miscarriage due to procedure is 1% (in addition to 2-3% background risk)
  - Some past studies have cited increased risk for transverse limb anomalies
    - When performed before 10 weeks
    - More recent studies do not indicate any increased risk when performed at 10-12 weeks
  - Some women with elevated MSAFP or unclear CVS results may be offered amniocentesis
  - Not recommended for women with following conditions
    - Active vaginal bleeding
    - Maternal bleeding disorder
    - Cervical polyps, active genital herpes or other infection (transcervical)
    - Interceding bowel or placenta far from maternal abdominal surface (transabdominal)

Amniocentesis

Performed after 15 weeks
Risks/Benefits
- 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 miscarriage due to procedure is 0.5%
- Incidence of mosaicism is 0.1-0.3%

Notes

The information for this outline was last updated in 2001.