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% 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. Notes The information in this outline was last updated in 2001.