Maternal Serum Screening

Any pregnancy can be at risk for birth defects including those that are not inherited from a child’s parents.  Conditions like Down syndrome, Open Neural Tube Defects (ONTD), and Trisomy 18  can affect any pregnancy, but a number of tests exist that can help determine the risk of one of these defects affecting a pregnancy.

What Tests Are Available?

GenPath offers several maternal serum screening tests that can be performed at specific times during a pregnancy.

First trimester only testing (11 to 13 weeks and 6 days)

COMBINED FIRST SCREEN 

Second trimester only testing (15 to 22 weeks and 6 days)

QUAD SCREEN

Integrated First and Second Trimester testing

INTEGRATED SCREEN 
SERUM INTEGRATED SCREEN
SEQUENTIAL SCREEN

The chart below contains information by test on detection rates (the percentage of affected pregnancies that will be found, “DR” in chart below) for a given screen positive rate (the chance that a woman’s test result will be considered at elevated risk, “SPR” in chart below).

TEST Down Syndrome Trisomy 18 ONTD
Combined First Screen DR 85% SPR 5% DR 90% n/a
Combined First Screen Plus DR 87% SPR 5% DR 90% n/a
Quad Screen DR 83% SPR 5% DR 77% 85% when using 2.5 MoM
Integrated Screen DR 95% SPR 2.15% DR >95% 85% when using 2.5 MoM
Serum Integrated Screen DR 92% SPR 5% DR 90% 85% when using 2.5 MoM
Sequential Screen 1st Tri: DR 62% SPR 0.6%
2nd Tri: DR 95% SPR 2.25%
1st Tri: DR n/a
2nd Tri: DR 95%
85% when using 2.5 MoM
  • WHAT IS DOWN SYNDROME?
    • Down syndrome is caused by an extra chromosome number 21 in the cells of the body and is the most common cause of intellectual disability, which can range from mild to severe. It is often associated with additional medical conditions including heart defects, gastrointestinal concerns, vision problems, hearing loss, and as characteristic facial features. There is no way to assess the degree of handicap before a child is born. About 9 of 10 babies with Down syndrome will survive their first year and nearly half of these will reach age 60. (Where is this statistic from – please confirm accuracy) . In an unscreened population, about 1 in 700 (1.4 in 100) babies are affected by Down syndrome. Down syndrome is usually not inherited, so a baby can be affected even if there is no family history of Down syndrome. While a woman of any age can give birth to a baby with Down syndrome, the risk of having an affected child increases as the woman’s age increases. For this reason, age is one of the factors used in determining the risk of your pregnancy. The risk for a pregnancy to be affected with Down syndrome can be modified based on the results of various screening tests during pregnancy. Diagnostic testing for Down syndrome is also available during a pregnancy.
  • WHAT IS A RISK?
    • A risk is the chance of an event occurring. For example, if the risk of a particular birth defect is 1 in 100, it means that out of 100 women with a particular test result, 1 of the pregnancies is expected to be affected by the defect (while the other 99 would not be affected.)
  • WHAT ARE OPEN NEURAL TUBE DEFECTS (ONTD)?
    • Two kinds of open neural tube defects (ONTDs) include spina bifida and anenencephaly. Open spina bifidais a defect where a baby has an opening in the spine that can cause damage to the nerves that control the lower part of the body. This can cause weakness or paralysis of the legs, as well as bowel and bladder problems. Closed spina bifidais a defect where the spinal opening is covered with skin or thick tissue. This accounts for about one in five babies born with spina bifida. While closed spina bifida cannot be detected by blood tests during pregnancy, the condition is often less severe than open spina bifida. Babies with spina bifida are more likely to suffer from a condition called hydrocephalus, where fluid collects on the brain. Although hydrocephalus can be treated surgically, it can potentially lead to intellectual disability.Anencephaly is a defect that is nearly always fatal either during the pregnancy or shortly after delivery. Babies born with this condition have a large part of their skull missing, and their brain is not properly formed.Anyone can have a baby with an open neural tube defect. However, individuals who have a NTD or couples who have already had a baby with a NTD have an increased risk of having another affected baby. In addition, women with certain health conditions, such as diabetes and those taking anti-seizure medications have an increased risk for children with open neural tube defects. Screening tests are available during pregnancy that can assess the risk for a woman to have a child with an open neural tube defect.
  • CAN OTHER ABNORMALITIES BE IDENTIFIED?
    • The risk of two other disorders can be estimated through maternal serum testing. Trisomy 18 is a rare and usually fatal disorder caused by an extra chromosome 18 in the cells of a developing baby. The risk of Trisomy 18 can be estimated using PAPP-A, AFP, uE3 and total ß-hCG. Smith-Lemli-Opitz syndrome(SLOS) is a genetic disorder that may cause developmental problems in a baby including mental retardation and poor growth. SLOS is caused by errors in how the baby synthesizes cholesterol.  The risk of SLOS can be estimated using AFP, uE3 and total ß-hCG. The results of Trisomy 18 and SLOS testing are reported only if the risk of a disorder is high.
  • WHAT DOES A SCREEN POSITIVE RESULT FOR DOWN SYNDROME MEAN?
    • A screen positive result means that you are at high risk for having a baby with Down syndrome. A result is called screen positive if the risk of Down syndrome in your pregnancy is greater than or equal to a cut-off number as determined by the type of screening test: The following is a list of cut-offs used by the laboratory for each test.

      Combined First Test –  1 in 200
      Quad Test – 1 in 270
      Integrated Test – 1 in 190
      Serum Integrated Test – 1 in 270
      Sequential Test (first trimester testing only) – 1 in 30
      Sequential Test (first and second trimester testing) – 1 in 190

      If you receive a screen positive result, genetic counseling is recommended to discuss available testing options, which may include the option of diagnostic testing like CVS or amniocentesis to determine whether the baby has Down syndrome.

      Note that a screen positive result does not necessarily mean that your baby will have Down syndrome.  Most women with screen positive results do not have a pregnancy with Down syndrome.

  • WHAT DOES A SCREEN NEGATIVE RESULT MEAN?
    • If the risk of Down syndrome is below the threshold risk level for the screening test, then the result is called screen negative. Although a screen negative means that you are not at high risk of having a baby with Down syndrome, trisomy 18 or an open neural tube defect, a screen negative result does not completely rule out the possibility of a pregnancy with one of these conditions. This is because a screening test cannot completely distinguish between an affected pregnancy and an unaffected one.
  • WHAT IS CHORIONIC VILLUS SAMPLING (CVS)?
    • CVS is typically performed between 10-13 weeks and 6 days of pregnancy. Depending upon the position of the placenta or based on other obstetrical considerations, CVS is performed either transcervically or transabdominally. With transcervical CVS, a thin catheter is inserted through the vagina and cervix under ultrasound guidance. The catheter is then guided to the edge of the developing placenta. With transabdominal CVS, a thin needle is inserted in a woman’s abdomen and is guided to the edge of the developing placenta. A small amount of the chorionic villi is removed from the developing placenta. These villi are finger-like projections that contain cells that are representative of the baby. This sample is sent to the laboratory for chromosome analysis or any other special genetic testing.
  • WHAT IS AMNIOCENTESIS?
    • Amniocentesis is typically performed between 15-22 weeks of pregnancy. It can also be performed at later stages in pregnancy, when indicated. Under ultrasound guidance, a thin needle is inserted into the woman’s abdomen and into the amniotic sac. A small amount of amniotic fluid is removed and sent to the laboratory for chromosome analysis or any other special genetic testing. Alpha-fetoprotein (AFP) is also found in the amniotic fluid and is measured to assess the risk for open neural tube defects.
  • WHAT ARE THE ADVANTAGES OF RISK ASSESSMENT?
    • Maternal serum screening and risk assessment provide you and your doctor important information about your pregnancy and your developing baby.  If your baby is found to have a serious birth defect, counseling will be offered to explain how your child’s physical and mental development will be affected.  You may wish to discuss the individual capabilities and potential of children with birth defects with your doctor or genetic counselor.   They will be able to discuss different options available to you and your partner.