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
 * 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-dependent 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 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%