Patient information: Second trimester screening for Down syndrome

INTRODUCTION

Down syndrome is the most common cause of severe learning disabilities in children, occurring in about 1 of every 700 births. Down syndrome is also called trisomy 21. There is no way to prevent Down syndrome, but it is possible to perform tests that indicate if a pregnant woman's developing fetus has an increased risk of Down syndrome.

Testing can be done at the end of the first trimester and/or at the beginning of the second trimester. The most accurate test is one that uses information from tests done during both the first and second trimesters (called integrated testing). There are advantages to each type of testing; second trimester screening for Down syndrome is discussed here.

There is a separate article that discusses first trimester and integrated screening for Down syndrome. (See "Patient information: First trimester and integrated screening for Down syndrome".)

An article is also available to help determine if testing for Down syndrome is right for you. (See "Patient information: Should I have a screening test for Down syndrome during pregnancy?".)

NORMAL GENETIC DEVELOPMENT

A brief description of normal genetic development will help to explain how Down syndrome occurs.

Normally, each person has 46 chromosomes. Chromosomes are made up of thousands of genes and are located inside all of the cells in the body. Genes direct all of the cell's activities, which include growth, development, and functioning of the body. At conception, a fetus inherits 23 chromosomes from the mother, and 23 from the father, totaling 46 chromosomes.

In the majority of cases of Down syndrome, there is an extra copy of chromosome 21, meaning that the individual has 47 chromosomes. The extra chromosome may come from either parent. A rare form of Down syndrome occurs in which a parent carries a subtle abnormality on chromosome 21 that, when passed on to an offspring, may cause Down syndrome.

In either case, a child who is affected will have moderate to severe learning disabilities, low IQ, a characteristic physical appearance (flat face, slanting eyes), and often have heart defects. Other problems can also occur. Although life expectancy was once substantially shortened, it is now possible for people with Down syndrome to live about 50 years.

RISK FACTORS FOR DOWN SYNDROME

Down syndrome is the most common chromosomal abnormality in newborns. It may affect any pregnancy, but some pregnancies are at higher risk than others. These groups include:

• Older women are at higher risk than younger women (table 1)
• Parents who have had a baby with Down syndrome
• Parents who have abnormalities involving chromosome 21

In addition, Down syndrome screening tests can indicate that a pregnancy may be at increased risk. The following discussion applies to women who undergo these tests.

Testing is available to determine a pregnant woman's risk of having a child with Down syndrome.

What is a screening test? — Screening tests measure chemicals in blood from the woman, and combine these results with the woman's age and sometimes with results of ultrasound testing of the fetus, to estimate risk. Screening tests do not diagnose Down syndrome; rather, the tests identify women who have an elevated risk of having a child with Down syndrome.

Prenatal screening tests for Down syndrome are voluntary, and about 60 percent of women in the United States undergo screening. Some parents choose prenatal screening and diagnostic tests to allow for the option of ending the pregnancy if the fetus is found to be affected. Other parents want advanced notice of the diagnosis so that they can prepare for the birth and care of a child with Down syndrome.

In 2007, the American College of Obstetricians and Gynecologists began recommending that all pregnant women consider a screening test for Down syndrome. The screening test provides some baseline information to consider before deciding to undergo diagnostic testing, such as amniocentesis or chorionic villus sampling, which has a risk of miscarriage.

Screening versus diagnostic testing — Prenatal diagnostic testing (eg, amniocentesis), rather than screening, should be considered by women of any age at increased risk of having a child with trisomy. (See "Patient information: Amniocentesis".) Such women include those with:

• A previous pregnancy complicated by a chromosomal abnormality
• A major fetal abnormality in the current pregnancy
• Chromosomal abnormalities in the woman or her partner

Choosing to be tested — Before undergoing prenatal tests, all pregnant women should understand the different types of tests, their risks and benefits, test accuracy, and the options available if the screening and/or diagnostic tests are positive.

The benefits of second trimester screening include the following:

• There is time for further testing (eg, amniocentesis) if the screening test is positive
• There is usually time to undergo termination after amniocentesis, if needed
• The woman and her family have time to prepare for a potentially complicated delivery and to understand the issues of raising a child with Down syndrome

Choosing not to be tested — Some women do not want to have a screening test, amniocentesis, or other testing for genetic abnormalities. It is important for each woman and her partner to discuss their wishes, values, and beliefs. The choice to pursue testing is highly individual. Common reasons to avoid screening for Down syndrome include the following:

• The woman is not willing to accept the potential risks, such as miscarriage, related to amniocentesis (needed to confirm the diagnosis if screening is positive)
• The woman is willing to wait until the baby's birth to find out if the baby has Down syndrome
• The woman would not terminate her pregnancy if the fetus had Down syndrome

Test timing — Blood tests to screen for Down syndrome in the second trimester are done between the 15th and 22nd week of pregnancy, ideally at week 15 or 16. It is important to have the test as early in this time frame as possible to ensure that there is sufficient time to receive genetic counseling, undergo additional testing if needed, and have a full range of options still available. Delaying the testing means that the pregnancy progresses further, which increases the risk of a termination procedure, if this is chosen.

Testing to screen for Down syndrome during the first trimester is available and is discussed separately. (See "Patient information: First trimester and integrated screening for Down syndrome".)

SECOND TRIMESTER SCREENING TESTS FOR DOWN SYNDROME

Triple screen versus quadruple screen — Tests of the mother's blood drawn during the second trimester may be used to estimate the risk of having a baby with Down syndrome. These blood tests measure normal substances (called markers) in the mother's blood that are secreted by the placenta or the fetus. The markers that are used in the screening process include alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A. Depending on the clinician and hospital, women are offered a triple screen, in which the AFP, uE3, and hCG are measured, or a quadruple screen, which adds the inhibin A measurement to the test. The quadruple screen is more accurate than the triple screen. (See 'Test accuracy' below.)

In pregnancies affected by Down syndrome, the markers often exhibit a characteristic pattern: levels of AFP and estriol in the mother's blood are, on average, 25 to 30 percent lower than normal, while hCG and inhibin A are two times higher than normal.

The blood levels of the markers are interpreted after considering the woman's age and other factors. (See 'Risk calculation' below.) All of the information is used together to calculate the woman's risk of carrying a baby with Down syndrome.

However, abnormal patterns can exist in a small percentage of normal pregnancies. Therefore, if the test suggests an increased risk of Down syndrome, further testing is needed to determine if a fetal abnormality is present and to identify the abnormality.

Risk calculation — A woman's individual risk is calculated from her age, the age of the fetus, and the results of the screening test. If there is any uncertainty about the gestational age of the fetus, an ultrasound examination will be recommended.

If the risk reaches or exceeds the cut-off level (usually 1 in 280), the test is considered "positive" or "increased risk". The actual risk of Down syndrome for a woman's pregnancy is expressed as a probability (eg, 1 in 5000 or 0.02 percent). There is no risk that guarantees that the baby does not have Down syndrome.

Other factors that can affect the results of the test include whether or not there was a Down syndrome pregnancy in the past, the woman's race, body weight, if she has a multiple gestation (twins, triplets, etc.), insulin-dependent diabetes, or if in vitro fertilization was used to achieve pregnancy.

Test accuracy — Approximately 70 percent of women who are carrying a baby with Down syndrome will have a positive triple screen (blood test that measures AFP, uE3, hCG) (table 2). This means that the test does not identify 30 percent of women who are carrying a baby with Down syndrome. About 5 percent of women who have the triple screen will have a false positive screening test. A false positive result means that the test is positive although the infant is not affected by Down syndrome.

 The quadruple screen (blood test that measures AFP, uE3, hCG, inhibin A) is the best screening test for Down syndrome during the second trimester. Approximately 80 percent of women who are carrying a baby with Down syndrome will have a positive quadruple screen (table 2). This means that the test does not identify 20 percent of women who are carrying a baby with Down syndrome. About 5 percent of women who have the quadruple screen will have a false positive screening test.

POSITIVE RESULTS

A positive result means that a woman's risk of having a child with Down syndrome is at or above a specific cut-off level. Screening tests do not indicate for certain if the baby is affected. Further testing is needed to definitively say if the child is affected.

Amniocentesis — The procedure used to diagnose Down syndrome during the second trimester is amniocentesis. Amniocentesis has a small risk of miscarriage; this means that for every 200 women who have an amniocentesis, approximately one woman will have a miscarriage.

Women who are considering an amniocentesis should meet with their clinician and a genetic counselor to discuss the risks, limitations, and benefits of diagnostic testing. Talking with a counselor can also help parents identify the issues involved in ending a pregnancy or raising a child with Down syndrome. (See "Patient information: Amniocentesis".)

Living with Down syndrome — Parents often wonder how Down syndrome will affect their child. A detailed article describes how Down syndrome can impact a child's health. (See "Patient information: Down syndrome".)

NEGATIVE RESULTS

A negative screening test means that a woman's fetus has no increased risk of Down syndrome, as compared to the fetuses of other women who are the same age. A negative screen does not mean that a baby does not have Down syndrome or another disorder (there is no screening test that guarantees this).

A woman who is at increased risk of having a child with Down syndrome who has a negative second trimester screening test may choose to meet with a clinician or genetic counselor to discuss the risks and benefits of further testing.

TESTING FOR OTHER DISORDERS

Sometimes, patterns in the screening test suggest other disorders, including neural tube defects (eg, spina bifida) or other chromosomal abnormalities. An obstetrician or genetic counselor can explain these results in detail, and describe what, if any, recommendations might be made based on the findings.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: First trimester and integrated screening for Down syndrome
Patient information: Should I have a screening test for Down syndrome during pregnancy?
Patient information: Amniocentesis
Patient information: Down syndrome

Professional Level Information:
Cytogenetic abnormalities in the embryo, fetus, and infant
First trimester and integrated screening for Down syndrome and trisomy 18
Management of Down syndrome

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• American College of Obstetricians and Gynecologists

  (www.acog.org)

• March of Dimes Birth Defects Foundation

  (www.marchofdimes.com)

• National Association for Down Syndrome

  (www.nads.org)

• National Down Syndrome Society

  (www.ndss.org)

• National Institute of Child Health and Human Development

  (www.nichd.nih.gov)

• National Library of Medicine

  (www.nlm.nih.gov/medlineplus/healthtopics.html)

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