Maternal Serum Screening, Second Trimester

Maternal serum screening is a group of tests used in the second trimester of pregnancy to help evaluate a woman’s risk of carrying a baby with chromosome disorders, including Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18), or neural tube defects such as spina bifida or a condition called anencephaly.

The tests are often combined into a triple or quad screen because their value lies in their use together. A mathematical calculation involving the levels of these substances (AFP, hCG, unconjugated estriol, and, sometimes, inhibin A) as well as considerations of maternal age, family history, weight, race, and diabetic status is used to determine a numeric risk for abnormalities in the fetus.

The second trimester maternal serum screen is one of the options that may be offered for prenatal screening for fetal abnormalities. Others options include the first trimester screen and cell-free fetal DNA (cffDNA) testing.

An AFP test may be performed by itself and not as part of a triple or quad screen, especially when first trimester screening or cffDNA testing has already been used to assess the risk for a chromosomal disorder. The AFP is used to help determine the risk of neural tube defects.

The screening approach a woman may choose depends on what technology is available and when she first seeks prenatal care. For more information about how maternal serum screening fits in with other screening options, see below.

Your health care practitioner may offer you the test between the 15th and 20th weeks of pregnancy.

A genetic counselor or health practitioner who can explain the meaning of the results and offer choices about follow up should interpret the screening results.

It is important to remember that positive screening tests are not diagnostic of a fetal abnormality. While they indicate an increased risk, only a small number of women who have positive maternal serum screening results have babies who actually have a neural tube defect or chromosomal abnormality.

In pregnancies where the fetus is carrying the chromosomal defect that results in Down syndrome (trisomy 21), the levels of AFP and unconjugated estriol tend to be low and hCG and inhibin A levels high.

In pregnancies where the fetus has Edwards syndrome (trisomy 18), unconjugated estriol and hCG levels are low and AFP levels can be variable.

A baby with an open neural tube defect has an opening in its spine or head that allows higher-than-usual amounts of AFP to pass into the mother’s blood. The other markers are not used in the evaluation of risk for carrying a fetus with a neural tube defect.

If a screen is positive, tests that are more definitive are needed to determine and confirm a diagnosis. These include high-resolution ultrasound and perhaps amniocentesis followed by chromosome analysis. These follow-up tests are used to help women and their health care practitioners make decisions about managing their pregnancies.

Screening will not detect all cases of fetal abnormalities.

The test result is very dependent on accurate determination of the gestational age of the fetus. If the gestational age of the fetus has not been accurately determined, the results may be either falsely high or low.

In multiple gestation pregnancies, calculation of the risk of Down syndrome or Edwards syndrome is difficult. For twin pregnancies, a “pseudorisk” can be calculated comparing results to normal results in other twin pregnancies.

Evaluation of the risk of open neural tube defects in twin pregnancies can be determined, although it is not as effective as in singleton pregnancies. For women further along in their pregnancies, risk cannot be calculated from these tests.

If you have had a first trimester Down syndrome screen, then second trimester maternal serum screening is typically not performed because the risks for Down syndrome and Edwards syndrome have already been assessed. However, if you and your healthcare practitioner wish to use the results of both first trimester and second trimester screening to assess the risk of chromosome abnormalities, then integrated or sequential screening may be employed. For more on these, see below.

Down syndrome (DS) is a chromosomal abnormality that is also called trisomy 21 because those with DS have an extra copy of part or all of chromosome 21. About 1 in 700 babies are born with Down syndrome each year in the U.S. The condition causes mild to moderate mental retardation and developmental problems and can be associated with congenital heart defects, respiratory and hearing problems, leukemia, and thyroid disorders. Many of the complications of Down syndrome can be treated and the lifespan of those affected has greatly increased in recent years. The risk of having a child with Down syndrome increases with the age of the mother. Although the risk of having an affected baby is significantly greater in those older than 35, the majority of Down syndrome babies (about 80%) are born to those under 35 because this age group has the greatest number of children. For this reason, the American College of Obstetricians and Gynecologists has recommended that all pregnant women be offered a screening test for Down syndrome.

Edwards syndrome (trisomy 18) is a condition in which there are three copies of chromosome 18. As with Down syndrome, the risk of carrying a fetus with Edwards syndrome increases with maternal age. Edwards syndrome is associated with multiple abnormalities and is usually fatal, with live-born infants rarely living beyond one year of age. The frequency of this abnormality is much less than that of Down syndrome, occurring in only 1 in 6,000 live births. For more information, see the Trisomy 18 Foundation web site.

Neural tube defects (NTDs) are serious birth defects in which the brain, spinal cord, or their coverings do not develop completely. They arise early in pregnancy, affecting fetal development, and can cause life-long complications of varying severity for the child. There are several types of neural tube defects, the most common of which are:

• Spina bifida: the most common neural tube defect; occurs when the neural tube does not close completely somewhere along the spine
• Anencephaly: occurs when the neural tube fails to close properly at the head; results in incomplete development of a large portion of the brain and the skull

The U.S. Public Health Service and the Centers for Disease Control and Prevention recommend that all women of childbearing age take 0.4 mg (400 micrograms) of folic acid daily. They recommend this to all women between the ages of 15 and 45 because many pregnancies are unplanned and neural tube defects occur very early in a pregnancy, before a woman may realize that she is pregnant. The recommended dose may be higher for women considered at high risk for having a baby with a neural tube defect, such as those who have already had an NTD-affected pregnancy. Folic acid can be found in fortified foods, supplements, and from a healthy, varied diet. For more information, see the CDC’s web page Facts About Folic Acid.

A newer test called cell-free fetal DNA (cffDNA) only requires a blood sample from the pregnant woman and can be used to screen for certain fetal chromosomal abnormalities, including Down syndrome, Edwards syndrome, and Patau syndrome (trisomy 13). It can be performed as early as the tenth week of pregnancy. It does not, however, screen for neural tube defects like spina bifida. Invasive diagnostic tests, such as chorionic villus sampling (CVS) and amniocentesis, are still needed to confirm the results of cffDNA. Since cffDNA screening is a relatively new test, some insurance companies may not cover it and it may not be available everywhere.

There are several approaches to screening depending on what technology is available where you are and when you first visit your health care practitioner for prenatal care. Options include:

• First trimester screening for chromosome abnormalities using the combined tests for pregnancy-associated plasma protein A (PAPP-A), hCG and nuchal translucency ultrasound, followed by a blood test for maternal AFP and/or a fetal ultrasound in the second trimester to check for neural tube defects

• Second trimester screening (triple or quad screen) to assess risk for chromosome abnormalities and neural tube defects; this may be the only testing done, especially in the case of a woman who does not visit her health care practitioner until the second trimester.

• Cell-free fetal DNA testing in the first or second trimester with a blood test for maternal AFP and/or a fetal ultrasound in the second trimester to check for neural tube defects

Typically, if first trimester screening for chromosome disorders has been performed, then screening in the second trimester is not performed because the risks for Down syndrome and Edwards syndrome have already been assessed. However, if you and your health care practitioner wish to use the results of both first trimester Down syndrome screen combined tests and the second trimester maternal serum screen to assess the risk of chromosome abnormalities, then one of the following approaches is used:

• Integrated screening – involves performing both first and second trimester testing and not releasing the results until all testing is completed

• Sequential screening – involves performing a first trimester screen; if the screen indicates increased risk for Down syndrome or Edwards syndrome, a diagnostic procedure such as chorionic villus sampling is offered. If the screen does not indicate increased risk, then a triple or quad screen in the second trimester is offered and results from both the first and second trimester screens are used in the final risk assessment.