Last modified on 18 June 2006, at 11:08

Handbook of Genetic Counseling/Maternal Serum Triple Screen-2

Maternal Serum Triple Marker Screening (Triple Screen)

ContractingEdit

  • What do you know about why you have been referred for genetic counseling?
  • What have you been told about the triple screen? What is your understanding of your test results?
  • What questions or concerns would you like to address?

Overview of maternal serum screeningEdit

  • 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)
        • Pregnancy hormone made by fetus and placenta
        • Level increases throughout pregnancy
      • Some laboratories also measure levels of inhibin-A
        • Product of placenta
        • Quadruple-marker screening may increase detection rate for Down Syndrome
    • Risk assessment
      • Markers are expressed as multiples of the median (MoM) in report
        • MoM determined by examining results from a large number of women and establishing an "average"
        • The median for all markers is 1.0 MoM
        • An individual's values expressed as marker level in patient/median marker level
      • Laboratory calculates a woman's risks based on levels of three substance plus other factors
        • Multiple gestations would cause levels to be elevated
        • Gestational age
          • Marker levels change throughout pregnancy
          • Inaccurate dates are common reason for false positive
          • Gestational age can be confirmed by ultrasound
        • Maternal weight
          • Increased weight means increased blood volume
          • Markers will be diluted in serum and their concentration lower
        • Maternal race
        • Maternal age
          • Increased risk for having child with chromosomal abnormality as maternal age increases
          • Women over age 35 have higher detection rate and false positive rate
        • Diabetic status
          • Insulin-dependant diabetics have increased risk for neural tube defects
          • Tend to have lower AFP levels, so use lower AFP cutoff
      • Evaluation of screening performance
        • Up to 100 of every 1,000 women who take test will have abnormal result
          • 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
          • Abnormal result could also be normal variation
        • Pattern of variation in levels may indicate that a woman is at increased risk for a particular birth defect
  • Evaluation of abnormal results
    • Elevated MSAFP
      • Greater than 2.5 MoM
      • Conditions possibly causing elevated MSAFP
        • Normal variant
        • Underestimation of gestational age
        • Multiple pregnancies
        • Open neural tube defects
        • Abdominal wall defects
        • Feto-maternal bleeding
        • Fetal demise
        • Finnish nephrosis
        • Some other birth defects
      • Increased risk for 3rd trimester complications
      • Follow-up strategies:
        • Repeat MSAFP
          • If patient's gestational age is within testable range
          • If only mild elevation (2.5-3.0 MoM)
        • Confirm gestational age by ultrasound
        • Offer ultrasound and amniocentesis
        • Serial ultrasounds and antenatal testing
          • If AFP greater than 3.0 MoM
          • When cause of elevation is not identified
      • Neural tube defects
        • Includes spina bifida, anencephaly most commonly
        • Also includes such conditions as encephalocele and hydrocephalus
        • Neural tube is part of developing embryo that brain and spine develop from
          • Neural tube defects due to failure of this tube to close properly
          • About 2,500 babies born each year in US with neural tube defect
        • Spina bifida
          • Backbone does not form properly
          • Often spinal cord is malformed and protrudes from back
          • Can cause leg paralysis and bladder and bowel problems
        • Anencephaly
          • Upper end of neural tube fails to close
          • Brain and skull severely malformed
          • Babies usually don't survive
        • Multifactorial inheritance
          • Both genetic and environmental factors interact to cause this condition
          • About 90-95% of babies with NTDs born into families with no prior history
    • Screen positive for Down Syndrome
      • Positive if calculated risk is greater than 1 in 270
      • Occurs when AFP is decreased, hCG elevated, and uE3 decreased
      • Conditions possibly associated with screen positive for Down Syndrome
        • Normal variant
        • Overestimation of gestational age
        • Multiple pregnancies (uncommon)
        • Down syndrome
        • Another chromosome abnormality
        • Triploidy
      • Increased risk for 3rd trimester complications
      • Follow-up recommendations
        • Confirm gestational age with ultrasound
        • Repeat test only if patient was at too early a gestational age for the screen to be performed
        • Offer diagnostic ultrasound and amniocentesis
        • Ultrasound for growth and monitoring for preeclampsia in 3rd trimester if hCG greater than 2.5 MoM for unknown reason
      • Down Syndrome
        • Explain chromosomes and nondisjunction
        • Discuss age-related risk and adjusted risk for Down syndrome
        • Clinical features and prognosis
          • Due to extra copy of chromosome 21
          • May cause characteristic facial features, mental retardation, heart defects, and other health problems
          • Cannot predict severity
    • Screen positive for Trisomy 18
      • When calculated risk is greater than 1 in 100
      • Occurs when AFP, hCG, and uE3 are all decreased
      • Conditions associated with positive screen
        • Normal variant
        • Gestational age inaccurate
        • Trisomy 18
        • Another chromosome abnormality
        • Fetal demise
        • Steroid sulfatase deficiency (X-linked ichthyosis)
      • Follow-up recommendations
        • Confirm gestational age by ultrasound
        • Repeat only is gestational age at time of screen found to be too early
        • Offer diagnostic ultrasound and amniocentesis
        • Monitor for preeclampsia and offer ultrasound in 3rd trimester if hCG above 2.5 MoM and no cause identified
      • Trisomy 18
        • Explain chromosomes and nondisjunction
        • Discuss age related and adjusted rates for trisomy 18
        • Clinical features and prognosis
          • Caused by extra copy of chromosome 18
          • Causes severe mental retardation and health problems
          • Usually fatal within first year of life
  • Capabilities and limitations of screening
    • Benefits
      • May provide reassurance that fetus does not appear to have certain birth defects
      • Can help woman manage pregnancy better
        • When problems detected, woman can prepare for delivery or treatment needed right after birth
        • Prepare mentally, emotionally, and socially for birth of child with birth defect
      • May help women over age 35 determine whether to have more invasive procedure
        • Negative screen may actually lower risk for chromosome abnormality
        • Women with negative screen may choose to avoid more risky procedure
      • Monitoring of women with abnormal test result may prevent 3rd trimester complications
    • Limitations
      • Not diagnostic test
        • False positive may produce unnecessary anxiety
        • Negative test does not mean fetus does not have birth defect, only that not at increased risk for conditions mentioned
      • May be no explanation for abnormal result
        • Abnormal results may be associated with pregnancy problems like placental abruption, preterm labor, and low birth weight
        • May cause maternal anxiety
      • Can't identify all birth defects
        • Down syndrome and Trisomy 18 are only chromosomal abnormalities that can be detected with this test
        • Amniocentesis is only way to diagnose or rule out chromosome problems

Other testing optionsEdit

  • Ultrasound
    • May be offered to confirm gestational age or identify multiple fetuses to help interpret triple screen results
    • Can detect many major birth defects
    • Can rule out 95% of NTDs if visualization is not limited
    • Can't diagnose chromosomal abnormalities
  • 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%

ReferencesEdit

  • 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 179-238.

NotesEdit

The information in this outline was last updated in 2001.