Maternal Blood Screening for Birth Defects

Maternal blood screening tests are blood tests that identify pregnancies that are at higher-than-average risk for certain serious birth defects, including Down syndrome, other chromosomal birth defects and neural tube defects (NTDs), which are defects of the brain and spinal cord. The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women regardless of age be offered a screening test for Down syndrome and certain other chromosomal birth defects (1). ACOG also recommends that all pregnant women have the option of choosing a diagnostic test for birth defects, instead of a screening test (1).

It’s important for pregnant women to understand the difference between a screening test and a diagnostic test.

  • Screening tests help evaluate the risk for certain birth defects, but they cannot diagnose a birth defect. Screening tests are noninvasive and pose no risk to mother or baby.
  • Diagnostic tests, such as amniocentesis and chorionic villus sampling (CVS), are highly accurate at diagnosing or ruling out a birth defect. However, these tests are invasive and may pose a very small risk of miscarriage.

Until recently, only women over age 35 and women considered at increased risk for having a baby with birth defects were offered diagnostic testing, rather than a screening test. Women over age 35 were considered at increased risk because the risk of chromosomal birth defects increases with a mother’s age. However, ACOG now recommends that providers offer women over age 35 the option of having a screening test to assess their risk before deciding whether or not to go ahead with amniocentesis or CVS (1).

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What disorders can screening tests detect?

  • Down syndrome: About 1 in 800 babies in the United States is born with Down syndrome, which is caused by an extra copy of chromosome 21 (2). Affected children have varying degrees of mental retardation, characteristic facial features and, often, heart defects and other physical problems.
  • Trisomy 18 (Edward syndrome): About 1 in 6,000 babies in the United States is born with trisomy 18, which is caused by an extra copy of chromosome 18 (3). Affected babies have severe mental retardation, heart defects and other birth defects. Most die in the first year of life.
  • NTDs: The neural tube is the structure that develops into the brain and spinal cord. If the neural tube does not close properly during the fourth week after conception, the baby has an NTD, such as spina bifida or anencephaly. About 1 in 1,000 pregnancies are affected by these birth defects each year in the United States (2).

    Spina bifida, often called open spine, affects the backbone and sometimes the spinal cord. Children with the severe form of spina bifida have varying degrees of leg paralysis and bladder and bowel control problems. Anencephaly is a fatal condition in which a baby is born with a severely underdeveloped brain and skull.

    If all women consumed the recommended amount of the B vitamin folic acid before and during early pregnancy, up to 70 percent of NTDs could be prevented (4). The March of Dimes recommends that all women of childbearing age take 400 micrograms of folic acid daily as part of a healthy diet.
  • Heart defects: In the United States, between 1 in 100 and 1 in 200 babies is born with a heart defect (2). The effects can range from mild to life-threatening. Many babies require surgery to help correct the defect.
  • Abdominal wall defects: Abdominal wall defects called gastroschisis and omphalocele each affect about 1 in 5,000 births in the U. S. (5). Affected babies have intestines that protrude outside the body through an opening in the abdominal wall or through a hernia in the umbilical area. Surgery can help correct these defects.

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What is the first-trimester screening test?
Some providers offer a first-trimester screening test for Down syndrome and trisomy 18. This test also may show if a baby is at increased risk for heart defects. The test is done between 11 and 13 weeks after a woman’s last menstrual period.

The test has two parts: a blood test and an ultrasound. The provider sends the blood sample to the lab to measure the levels of two substances in the mother’s blood:

  • Free beta-hCG, a specific form of the pregnancy hormone human chorionic gonadotropin
  • Pregnancy-associated plasma protein A (PAPP-A)

With Down syndrome, levels of PAPP-A tend to be decreased and hCG increased.

The woman also has an ultrasound to measure the thickness at the back of the baby’s neck (called nuchal translucency). Increased thickness is associated with Down syndrome, other chromosomal abnormalities and heart defects.

The lab calculates a woman’s risk of chromosomal birth defects using the combined results of her blood test and ultrasound. First-trimester screening can detect about 82 to 87 percent of pregnancies affected by Down syndrome and about 90 percent of those affected by trisomy 18 (1, 6).

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What is the second-trimester screening test?
Many providers offer a second-trimester screening test, which is done 15 to 20 weeks after a woman’s last menstrual period. This test has a number of names, including maternal serum (blood) screening test, multiple marker screening test, triple screen and quad screen. This test screens for NTDs, chromosomal birth defects and abdominal wall defects.

This test currently measures the levels of three or four substances in the mother’s blood. When maternal blood screening first began in the early 1980s, the test measured only alpha-fetoprotein (AFP), a substance produced by the liver of the fetus. Some of this protein passes into the amniotic fluid surrounding the fetus and into the mother’s bloodstream, where its concentration rises gradually until late in pregnancy.

Along with maternal serum alpha-fetoprotein (MSAFP) levels, the test now measures the levels of hCG and another pregnancy hormone called estriol. When the test measures these three substances, it’s called the triple screen.

Most labs in the United States measure the level of a fourth hormone called inhibin A. When this substance is included, the test is called a quad screen. Studies show that adding inhibin A to the test makes it more accurate than the triple screen in detecting Down syndrome (about 80 percent vs. about 70 percent) (1). Both the triple and quad screen can detect about 75 to 80 percent of pregnancies affected by spina bifida and nearly 95 percent of those with anencephaly (7).

The lab calculates a woman’s risk for NTDs, Down syndrome and trisomy 18 based on the levels of the three or four substances plus the woman’s age, weight, race, number of fetuses (e.g., twins) and whether she has diabetes that requires insulin treatment.

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Do some women have both a first- and second-trimester screening test?
Women who have the first-trimester screening test for Down syndrome should be screened for NTDs in the second trimester by checking MSAFP levels or having an ultrasound (1).

Providers may offer women the option of taking both the first- and second-trimester screening tests for chromosomal problems. These tests together can detect about 95 percent of cases of Down syndrome (1, 6). There are three approaches to combined first– and second-trimester screening:

  • Integrated screening test
  • Stepwise sequential screening test
  • Contingent screening test

In the integrated screening test, the woman receives her test results in the second trimester after all tests are completed.

In the stepwise sequential screening test, the woman receives results after each test. The woman is offered diagnostic tests if results of the first-trimester test or her combined first- and second-trimester test results show her baby is at increased risk for birth defects.

In the contingent screening test, the woman receives her test results after the first trimester test. No further testing is recommended if the test shows her baby is at low risk for chromosomal birth defects. She is offered diagnostic tests if results show her baby is at high risk for birth defects and a second-trimester screening test if results show an intermediate risk.

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What do screening test results mean?
A woman may receive her test result as a ratio. For example, her baby has a 1 in 500 risk for Down syndrome. A woman can use this information to help decide whether or not to go ahead with diagnostic testing.

In some cases, a woman’s test results are reported as normal (screen negative) or abnormal (screen positive), depending on whether her results fall below or above a cut-off point (usually about 1 in 270). Women should remember that screening tests cannot diagnose a birth defect; they only can indicate increased risk.

An abnormal screening test result simply means that additional testing is recommended. Out of every 100 women who take a screening test, about 5 (5 percent) have an abnormal result. However, only about 4 to 5 percent of women whose test results show an increased risk for Down syndrome actually have a baby with Down syndrome (8). Similarly, only a small number of women whose test results show an increased risk for spina bifida and related birth defects actually have an affected baby.

For many women, an abnormal result on the second-trimester screening test indicates that the fetus is either a few weeks older or younger than the woman and her provider thought. This can account for an abnormal result because AFP varies, depending on a woman’s stage of pregnancy. An ultrasound can usually show the correct gestational age of the fetus. Another common cause of an abnormal second-trimester test result is a multiple pregnancy (twins, triplets, etc.).

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What diagnostic tests are offered following an abnormal screening test result?
Women who have abnormal results on a first-trimester screening test should be offered genetic counseling and the option of CVS or second-trimester amniocentesis. CVS is usually done between 10 and 12 weeks of pregnancy. During CVS, the provider obtains a small tissue sample from the placenta by placing a slim tube in the vagina or by inserting a needle into the woman’s abdomen. The tissue sample is tested for Down syndrome and other chromosomal abnormalities. Some women with an abnormal first-trimester screening test result may be offered a special ultrasound called an echocardiogram to look for fetal heart defects.

For women with abnormal results on a second-trimester screening test, the next step often is an ultrasound. This test can check the gestational age of the fetus and show if a woman is carrying multiples. If either of these factors accounts for the abnormal test result, no further testing is needed. If ultrasound does not explain the abnormal test result, the provider recommends further diagnostic tests.

If the second-trimester screening test suggests an increased risk for Down syndrome or trisomy 18, the provider offers a woman amniocentesis. This test is done at 15 to 20 weeks of pregnancy. The provider inserts a thin needle through the abdominal wall and into the uterus to withdraw a few teaspoons of amniotic fluid. Fetal cells in the fluid are tested for chromosomal abnormalities.

If second-trimester screening shows that a woman is at increased risk for having a baby with an NTD, her provider may recommend a targeted ultrasound, amniocentesis or both. A targeted ultrasound of the fetal skull, spine and other organs can detect or rule out serious NTDs and help predict the severity of NTDs.

If this type of ultrasound is not available, or if more information is needed after the ultrasound, the provider often recommends amniocentesis to measure the level of AFP and other substances in the amniotic fluid. When amniocentesis is done to help detect NTDs, cells from the fetus usually are tested for chromosomal abnormalities because they sometimes can accompany an NTD or an abdominal wall defect.

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What are the benefits of maternal screening tests?
For most women, a screening test provides reassurance that their fetus does not appear to have certain serious birth defects. Test results also can help a woman manage her pregnancy more effectively. For example, finding the correct gestational age helps determine whether the fetus is growing at a normal rate. And detecting a multiple pregnancy allows for special care.

When an NTD or other problems are diagnosed or suspected, a woman can discuss all her options with her health care provider. She can plan for delivery in a specially equipped medical center so that the baby can have any surgery or treatment required soon after birth.

In some cases, there is no clear-cut explanation for an abnormal screening test result. Some abnormal results have been linked with pregnancy problems, such as preterm labor (labor before 37 completed weeks of pregnancy), low birthweight and stillbirth (9). If a woman has an unexplained abnormal screening test result, her provider may monitor her carefully in the last trimester of pregnancy. She may need more frequent prenatal visits and various tests of fetal well-being, such as ultrasound.

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References

  1. American College of Obstetricians and Gynecologists (ACOG). Screening for Fetal Chromosomal Abnormalities. ACOG Practice Bulletin, number 77, January 2007.
  2. Centers for Disease Control and Prevention (CDC). Birth Defects: Frequently Asked Questions. Updated 7/18/07.
  3. National Institutes of Health (NIH). Genetics Home Reference: Trisomy 18. Published 9/5/08.
  4. Centers for Disease Control and Prevention (CDC). Folic Acid: PHS Recommendations. Updated 7/26/05.
  5. Children’s Hospital of Philadelphia. Your Child’s Health. Accessed 9/9/08.
  6. Malone, F.D., et al. First-Trimester or Second-Trimester Screening, or Both, for Down’s Syndrome. New England Journal of Medicine, volume 353, number 19, November 10, 2005, pages 2001-2011.
  7. Norem, C.T., et al. Routine Ultrasonography Compared with Maternal Serum Alpha-Fetoprotein for Neural Tube Defect Screening. Obstetrics and Gynecology, volume 106, number 4, October 2005, pages 747-752.
  8. Simpson, J.L. Prenatal Screening Isn’t Perfect. Contemporary Ob/Gyn, February 2007, page 116.
  9. Smith, G.C.S. Pregnancy-Associated Plasma Protein A and Alpha-Fetoprotein and Prediction of Adverse Perinatal Outcome. Obstetrics and Gynecology, volume 107, number 1, January 2006, pages 161-166.

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November 2008