Genetic counseling: Maternal Serum Triple Screen

Maternal Serum Triple Screen

Introduction

 * Acknowledge any prior contact
 * Ask them what they know already about why they are here and what they hope to get out of the session
 * Address any immediate concerns or indicate that they will be addressed later during the discussion
 * Reassure them that this is not a diagnostic test so it can't tell us if there is a problem with the fetus or not. A triple screen is performed to pick out a smaller group of pregnancies that are at an increased risk for specific birth defects and to offer diagnostic testing.
 * The majority of women with a positive screen will have babies without birth defects
 * This does not mean the test was wrong because all it was supposed to do is pick out fetuses at higher risk and allow us to offer diagnostic testing.

Obtain Medical and Family History

 * It is helpful for me to know some information about your medical history as well as your family history to determine if there are any health problems that may run in the family. (Make sure all the following information was correct on the test report before the visit or while taking the history because it can change the results drastically.)
 * Gestational age - marker levels change throughout pregnancy and inaccurate dates are a common reason for a false positive
 * Maternal weight - with increased blood volume, the markers will be diluted in the serum and lower their concentrations
 * Maternal race - African American women typically have a 10-15% higher [AFP], but a lower incidence of NTD's
 * Maternal age - the detection rate and false positive rate for Down syndrome will both be higher in women over age 35
 * Diabetic status - Insulin-dependent diabetics have an increased risk of NTD's, but lower [AFP]
 * number of fetuses - increases marker levels

General Information about Triple Screen

 * A triple screen is a blood test that is routinely offered to women under age 35 where amniocentesis is not recommended.
 * It is performed between 14-22 weeks gestation (It is most accurate when performed between 16-18 weeks)
 * A negative or normal screening result does not ensure that a child will not have a birth defect
 * As mentioned before, a positive result is not a diagnosis of an abnormality. It only indicates that a person has a high enough risk to warrant further testing.
 * It is easy to get confused when discussing the triple screen because there is a lot of information so please interrupt me and ask questions as they come up or let me know if something is unclear

What a Positive Test Means

 * A positive test can tell whether you are at an increased risk for any of 3 disorders, but it can't tell you whether or not the fetus is actually affected
 * Open Neural Tube Defects
 * Give spina bifida as an example (where the spinal cord didn't form properly and nervous tissue is exposed)
 * Can cause motor impairments along with other health concerns
 * Does not detect all types of NTDs
 * If at high risk mention anencephaly so they can be prepared (where the brain is not formed properly and it is exposed) They may survive to term but die shortly after.
 * Explain whether their test showed that they were at increased risk or reassure them that their risk is not increased above the general population risk
 * Trisomy 18 and Trisomy 21
 * Explain chromosomes
 * When there is an extra chromosome it is called trisomy
 * Extra genetic material can cause problems in growth and development
 * There are a few relatively common trisomies, but the triple screen can detect only two of these
 * Explain the features and prognosis of trisomy 18 and Down syndrome
 * Explain whether or not their test showed they are at an increased risk for these

How Does Screening Work

 * Products made by the fetus and placenta can be detected in the mother's blood during pregnancy.
 * Levels of these products, referred to as markers, change throughout pregnancy
 * Increased or decreased levels of these markers can be correlated to an increased risk of any of the three types of problems that were discussed previously.
 * Triple screen measures three markers
 * AFP (alpha-fetoprotein --made in the liver and GI tract of the fetus) It is excreted into fetal urine, thus amniotic fluid, then transferred across placenta into maternal blood it increases during 2nd trimester
 * hCG (human chorionic gonadotropin - made by the placenta peaks at 10 weeks and falls from there) Pregnancy hormone tested for in pregnancy tests. Important marker for Down syndrome (increased)
 * uE3 (unconjugated estriol) - made by the fetus, placenta, and mother it increases throughout pregnancy-- found in both pregnant and nonpregnant women, but at different levels)

Risk Assessment

 * When the levels of the three markers are determined they are compared to the general population of pregnant women
 * The computer takes all factors into account, such as age of the mother and gestational age, to calculate a number (MoM - multiple of the median) that allows us to readily see if the levels are higher or lower than expected
 * A value that is 1 means that particular marker is present at expected levels
 * However most women do not receive 1's for all three markers and a little variation is common
 * It is not bad for the fetus to make different amounts of these proteins, but it is concerning if there are particular patterns to the levels of these three markers.
 * A value of 2 indicates that the levels are twice the average expected amount
 * A value of ½ indicates that the levels are half the average expected amount
 * When risks are determined, all three numbers are looked at together to look for a pattern that may indicate an increased risk for the three specific abnormalities we mentioned already

Interpreting What Your Results Mean

 * screen positive tests for singletons of non-diabetic mothers

ONTD

 * Only one marker is used to screen for ONTDs.
 * Positive screen if MSAFP is greater than or equal to 2.5 MoM
 * This indicates an unspecified increased risk of having a child with an ONTD
 * (The population incidence is 1 or 2 per every 1000 fetuses)

Trisomy 18

 * All three markers tend to be lower than expected, but uE3 is the most sensitive marker for trisomy 18.
 * The computer program takes your age related risks of having a child with trisomy 18 and calculates a new risk based on all the information
 * Your age related risk is _______________________
 * Your calculated new risk is _____________________ which means that the chance your fetus does not have trisomy 18 is ____________
 * The test is considered to be a positive screen if your new risk is greater than or equal to 1 in 100

Down syndrome

 * Markers tend to show the pattern in the chart above, but the most important predictive marker is hCG and it tends to be present in higher levels when the fetus has Down syndrome (reason unknown)
 * The computer program takes your age related risks of having a child with Down syndrome and calculates a new risk based on all the information
 * Your age related risk is _______________________
 * Your calculated new risk is _____________________ which means that the chance your fetus does not have Down syndrome is ____________
 * The test is considered to be a positive screen if your new risk is greater than or equal to 1 in 270 (approximate risk in women age 35 of having a fetus with Down syndrome at time of amnio)

Reasons for a Screen Positive Result

 * ONTD -- Other conditions can be associated with an elevated MSAFP

ONTD

 * Normal variant
 * Underestimated gestational age
 * Multiple pregnancy
 * Abdominal wall defect (gastroschisis or omphalocele)
 * Feto-maternal bleeding
 * Fetal demise
 * Other birth defects
 * Increased risk for 3rd trimester complications

Trisomy 18

 * Trisomy 18
 * Normal variant
 * Inaccurate dating (uE3 levels most predictive)
 * Another chromosome abnormality
 * Fetal demise
 * Steroid sulfatase deficiency (X-liked icthyosis) common reason if estriol is undetectable

Down Syndrome

 * Down Syndrome
 * Normal Variant
 * Gestational age (if GA off by more than 10 days should recalculate)
 * Multiple pregnancy
 * Another chromosomal abnormality
 * Triploidy
 * Increased risk of third trimester complications (if hCG > 2.5 she should be monitored more closely)

ONTDs

 * Offer ultrasound -
 * confirm gestational age (MSAFP increases throughout this time in pregnancy and the g.a. may just be underestimated)
 * rule out anencephaly, ONTD, fetal demise, multiple gestation
 * If nothing is found on ultrasound and dates are correct
 * 2.0-2.9 MoM, g.a. <18 wks repeat serum AFP
 * >3 MoM, or g.a. > 18 wks offer amnio (measures AFP 90-96% accurate and can also measure Acetylcholinesterase level which detects 99% of ONTD) also detects chromosomal abnormalities
 * If the cause of the elevation is still not identified and AFP was greater than 3.0 MoM, serial ultrasounds and antenatal testing should be considered (watch for pre-eclampsia)

Trisomy 18

 * Offer ultrasound
 * Confirm gestational age - off by >10 days call and get a recalculation (uE3 most important increases with gestational age)
 * Explain what they look for that might provide clues as to whether the fetus is affected (not diagnostic though so it cannot tell us for sure whether or not the fetus has trisomy 18)
 * Offer amniocentesis
 * diagnostic testing that will accurately determine if the fetus has trisomy 18 with greater than 99% accuracy
 * risks of miscarriage 0.5 % above baseline
 * also detects various other chromosomal abnormalities
 * If hCG is <2.5 MoM and cause is not identified, a third trimester ultrasound for growth should be considered and patient monitored for pre-eclampsia

Down syndrome

 * Offer ultrasound
 * Confirm gestational age
 * if off by 10 days or more and drawn before 15 weeks than repeat at 15-18 wks
 * if off by 10 days of more and drawn at or after 15 wks than recalculate the DS risk using corrected age
 * Explain other things they will look for on the ultrasound that may be signs of Down syndrome
 * Signs are found on ultrasound in about 2/3 of fetuses with Down syndrome
 * Whether or not signs are found ultrasound cannot confirm for certain whether or not the fetus is affected.
 * Offer amniocentesis (diagnostic testing that will tell us whether the fetus has Down syndrome with >99% accuracy and also detects other chromosomal abnormalities
 * If hCG is <2.5 MoM and cause is not identified, a third trimester ultrasound for growth should be considered and patient monitored for pre-eclampsia

Triple Screen Sensitivity

 * Focus on their results
 * These statistics are for the population and don't really affect their results
 * They may be confused about this though so address it if there are questions
 * Detection rate
 * Given the fetus is affected detection rate is the chance that it will be picked up and have a positive screen.
 * NOT ALL AFFECTED FETUSES ARE PICKED UP ON TRIPLE SCREEN
 * False positive
 * Chance of having an unaffected fetus and obtaining a positive screen out of all unaffected pregnancies
 * Since there are more unaffected pregnancies than affected pregnancies it may seem like there is a large absolute # of false positives
 * If their fetus is unaffected it doesn't meant that the triple screen was wrong because all it is supposed to do is pick out women at increased risk for NTDs, Down syndrome, and trisomy 18.

ONTDs

 * 85% detection rate - means that out of 100 pregnancies where the fetus has an ONTD 85 of them are picked up by this screening (it does not pick up closed neural tube defects)
 * 80% of cases of open spina bifida
 * 90% of cases of anencephaly

Trisomy 18

 * 60-80% detection rate - means that out of 100 pregnancies where the fetus has trisomy 18, 60 or 80 of them will be picked up as a positive screen
 * .5% false positive rate - means that out of 200 women who are carrying a fetus without trisomy 18 1 of those 200 would receive a positive screen

UNDER 35

 * 60-65% detection rate - means that out of 100 pregnancies where the fetus has Down syndrome about 65 will be picked out by this screening
 * 5% false positive rate - means that out of 100 women that do not have a child with Down syndrome 5 of them will receive a positive screen

OVER 35

 * 85-90% detection rate
 * 25% false positive rate

Review

 * Assess if there are any questions or if there is anything that she would like me to explain again
 * Assess how she feels about further testing options
 * Check for understanding by having her explain how she feels about her risk