Handbook of Genetic Counseling/First Trimester Screening

First Trimester Screening

Overview

• Screen low-risk population to identify those at higher risk to give birth to child with a chromosome abnormality
  • Normal result does not mean that there are no abnormalities
  • Abnormal result indicates that diagnostic testing by amniocentesis or CVS is warranted
• Consists of ultrasound and blood test
• Performed between 10th and 14th week of pregnancy

Procedure

• Biochemical screening
  • Blood draw done by finger stick onto filter paper
  • May be taken between 8 weeks, 4 days and 13 weeks, 3 days
  • Measures levels of substances found in the blood of all pregnant women
    • FreeBeta Human chorionic gonadotropin (hCG) measurements
      • Glycoprotein derived from the placenta
      • Serum levels tend to be high in patients carrying a fetus affected with Down Syndrome (average = 1.9 MoM)
      • Serum levels significantly reduced in patients carrying a fetus affected with Trisomy 18 (average = 0.18 MoM)
    • Pregnancy Associated Plasma Protein A (PAPP-A)
      • Produced by trophoblast of placenta
      • Significantly reduced in blood of women carrying fetuses with Down Syndrome (average = 0.44 MoM)
      • Significantly reduced in blood of women carrying fetuses with Trisomy 18 (average = 0.32 MoM)
• Ultrasonagraphic findings
  • Measure nuchal translucency (NT)
    • Amount of fluid that accumulates behind the neck of the baby
      • Echo-free space between skin and soft tissue overlying cervical spine
      • Present only during first trimester
    • About 30-86% of fetuses with increased nuchal translucency have chromosomal abnormality
    • Increased in fetuses with chromosome abnormalities, cardiac defects, and certain genetic syndromes
      • Greater than 3.5 mm is considered out of normal range
      • Increased NT is not diagnostic of chromosome abnormality
      • Lymphedema seen in NT may be result of fetal cardiac abnormalities
    • Usually resolves in second trimester
    • No consensus on how to measure nuchal translucency resulting in conflicting results about effectiveness
  • Measured transbdominally in 95% of cases and transvaginally in other 5%
  • Procedure takes between 15 and 30 minutes

Detection Rate

• Biochemical screening without NT
  • Identifies greater than 60% of Down Syndrome
  • Identifies 90% of Trisomy 18
  • About 1 in 25 women with an increased risk based on screening will have baby with Down Syndrome
• Biochemical screening with NT
  • Identifies about 90% of Down Syndrome
  • Identifies up to 97% of Trisomy 18
  • False positive rate is 5%
  • About 1 in 17 women with an increased risk based on screening will have baby with Down Syndrome
• Cannot screen for open neural tube defects so AFP testing still recommended in 2nd trimester
• Cannot identify all birth defects

Benefits and Limitations of Testing

• Benefits
  • Helps reduce maternal anxiety at earlier gestational age
  • Allows patient to have CVS for diagnosis in 1st trimester
  • Allows for 1st trimester termination of affected fetus
  • Not an invasive procedure - no risk to mother or to fetus
• Limitations
  • Currently not covered by insurance
  • Only screens for two out of possible thousands of genetic conditions
  • Screening will miss about 10% of Down Syndrome
  • Still requires invasive procedure for diagnosis
  • Not as sensitive if multiple pregnancies
  • Patient specific risks rely on accuracy of clinical information that is interpreted for results of test

Research Study at Magee-Womens Hospital

• Eligibility criteria: women 18-45 between 10 and 14 weeks
• To determine if first trimester screening is an effective method to detect Down Syndrome and other chromosome abnormalities
  • If risk higher than 1 in 270, can continue routine prenatal care, undergo CVS at 10-13 weeks, or have amniocentesis after 15 weeks
  • Women who choose to participate must provide information on pregnancy outcome
• Responsible for all costs, including blood sample, ultrasound, and genetic counseling

References

• "ACOG Committee Opinion: First Trimester Screening for Fetal Anomalies with Nuchal Translucency." American College of Obstetrics and Gynecology. http://www.medem.com
• "NIH News Release: First Trimester Screening for Down Syndrome Possible, NICHD-Funded Study Finds." National Institutes of Health. http;//www.nih.gov
• "Screening for Down Syndrome, Trisomy 18 Syndrome, and Open Neural Tube Defects in the First Trimester." GeneCare Medical Genetics Center". http://www.genecare.com
• Spencer K. "Accuracy of Down Syndrome Risks Produced in a First-Trimester Screening Programme Incorporating Fetal Nuchal Translucency Thickness and Maternal Serum Biochemistry." Prenatal Diagnosis (2002) 22;244-246.

Notes

The information in this outline was last updated in June 2002.