Handbook of Genetic Counseling/Maternal Serum Triple Screen-2
Maternal Serum Triple Marker Screening (Triple Screen)
Contracting
- 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 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)
- 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
- Alpha-fetoprotein (AFP)
- 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
- Up to 100 of every 1,000 women who take test will have abnormal result
- Markers are expressed as multiples of the median (MoM) in report
- Screening test
- 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
- Repeat MSAFP
- 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
- Elevated MSAFP
- 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
- Not diagnostic test
- Benefits
Other testing options
- 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%
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 179-238.