Triple test

What it is

The triple test consists of three screening tests that can assess your risk of having a baby with certain defects. It looks at levels of three substances normally present in the bloodstream of a pregnant woman. The tests measure:

• Maternal serum alpha-fetoprotein (MSAFP), which evaluates the levels of alpha-fetoprotein (AFP) in your blood. AFP is a protein produced by your baby's liver. Small amounts of the protein cross through the placenta and amniotic fluid and show up in your blood.

• Human chorionic gonadotropin (HCG), a hormone produced by the placenta.

• Estriol, an estrogen produced by both the baby and the placenta.

The triple test, also known as the multiple marker screen, is used to screen for:

• Chromosomal disorders, such as Down syndrome (trisomy 21)

• Spinal abnormalities (neural tube defects), such as spina bifida

When it's administered

These tests may be offered to you between the 15th and 22nd weeks of your pregnancy. Levels of these chemicals change substantially as your baby continues to develop, so it's critical that the calculated age of your baby is correct. The MSAFP test is most accurate when done between the 16th and 18th weeks of gestation.

How it's done

The substances to be evaluated can be measured from a sample of your blood. To obtain a sample, a nurse or technician will probably draw blood from a vein inside your elbow or the back of your hand.

What the results may tell you

Low levels of MSAFP and estriol along with high levels of HCG may indicate the possibility of Down syndrome. Use of all three tests combined can detect 60 percent to 70 percent of babies with Down syndrome.

Some laboratories use another protein produced by both mother and baby (inhibin A) in addition to the triple test or instead of estriol. In one study, use of the inhibin A test increased the detection rate of Down syndrome to 85 percent. The overall risk of having a baby with Down syndrome is one in 1,000, but this risk increases with the age of the mother.

Low levels of all three substances may indicate trisomy 18, a chromosomal abnormality characterized by three number 18 chromosomes. Trisomy 18 typically causes severe deformity and mental retardation. Most babies with trisomy 18 die within their first year. The risk of having a baby with trisomy 18 is very low — only one in 6,000 live births.

By itself, the MSAFP test screens for spinal abnormalities such as spina bifida. High levels of MSAFP in your blood may indicate the presence of a neural tube defect, most commonly spina bifida or anencephaly. Spina bifida occurs early during fetal development when tissue fails to close over the spinal cord, leaving an opening in the baby's body. Anencephaly occurs when tissue fails to cover over the baby's brain and head. The rate at which these defects occur is low. Out of 1,000 women who undergo MSAFP screening, between 25 and 50 women have results that are higher than normal. Only about two of the 1,000 have babies with a neural tube defect, roughly half with spina bifida and half with anencephaly.

About 93 percent of women who undergo MSAFP screening have normal results. Of the pregnancies showing abnormal MSAFP levels, only about 2 percent to 3 percent result in birth defects.

Abnormal MSAFP levels may occur for several other reasons, including:

• Miscalculation of how long you've been pregnant. If the gestational age of your baby has been calculated incorrectly, the interpretation of MSAFP levels may be affected. MSAFP levels normally increase during the first 20 weeks of pregnancy. If you're later in your pregnancy than you thought, your blood will contain higher levels of MSAFP than expected. If earlier, MSAFP levels may be lower than expected.

• A multiple birth. Two or more babies will produce more MSAFP than one.

• Problems with the placenta. A defect in the placental wall that allows the baby's blood to enter your circulation will allow additional MSAFP

into your bloodstream. This may happen occasionally in pregnant women who have high blood pressure or who have another illness that affects the placenta.

• Failure to account for other factors. Your age, weight, race and whether you have type 1 diabetes (formerly called juvenile or insulin-dependent diabetes) each may affect MSAFP levels.

• Other defects. Any area that hasn't closed completely, such as with an abdominal wall defect, will increase the levels of MSAFP in the amniotic fluid and, eventually, your blood. Other reasons for elevated MSAFP include certain skin conditions, kidney problems and loss of the fetus.

Possible concerns

The biggest concern for most mothers is the anxiety caused by waiting for the results of the test, which take a few days. Most of the time, results come back negative, meaning no increased risk of abnormalities has been found. That doesn't mean your risk of having a baby with a problem is zero, but rather that your risk is about the same as that found in the general population (3 percent).

About 7 percent of the time, results will be positive, and additional, more-invasive and riskier tests will be offered. Still, most women within this positive group have normal babies.

Reasons to have it done

If you're concerned about your baby's health, negative results may provide you with reassurance. If you receive positive results, you can talk to your health care provider or a genetic counselor about your options. Knowing about possible problems before birth can give you time to make any necessary arrangements. You may plan to give birth at a hospital with the resources to care for your newborn. Some women faced with a severe abnormality in the fetus may choose to end the pregnancy.

What happens next

If you have negative results, no further testing is needed. If your results come back positive, you'll likely be offered additional testing. Occasionally, it makes sense to repeat the test. In most cases, further evaluation will take place in any event.

Most likely, your health care provider will recommend an ultrasound exam. This helps to establish the correct duration of the pregnancy and stage of development of your baby. It may also determine whether you're carrying twins or other multiples. Your health care provider can also examine the fetus for visible defects or other structural problems, which can often be seen during an ultrasound.

If your triple test indicates a high risk of chromosomal abnormality, amniocentesis may be used to obtain fetal cells to check for Down syndrome or another abnormality.

If a baby has spina bifida, 95 percent to 97 percent of the time the defect will be visible on ultrasound at 18 weeks. If your MSAFP levels are high and the ultrasound is normal, amniocentesis may be offered to check the amniotic fluid levels of MSAFP. If the amniocentesis indicates that MSAFP levels are high, the chances that your baby has a neural tube defect are very high. Measuring a chemical in the fluid called acetylcholinesterase can confirm the presence of a neural tube defect. Your health care provider may recommend another ultrasound. It may help determine the location and extent of the defect so that you can have more accurate counseling about the problems your baby may have.

Accuracy and limitations of the test

The triple test can detect Down syndrome 60 percent to 70 percent of the time, with a false-positive test result rate of about 5 percent. The MSAFP test can detect spina bifida about 80 percent of the time and anencephaly about 90 percent of the time.

What's new in prenatal testing?

Efforts to improve prenatal testing have opened the door to earlier diagnosis, which many women seek. Data suggests two tests — first-trimester proteins and nuchal translucency — may be helpful in providing early pregnancy screening. A third test, pre-implantation genetic diagnosis, offers testing for parents using in vitro fertilization (IVF). Availability of these tests may be limited, but it's likely to increase.

Like all screening tests, these two tests require confirmation with a diagnostic test such as chorionic villus sampling (CVS) or early amniocentesis.

First-trimester proteins

Two proteins appear in the first trimester: free beta-human chorionic gonadotropin (beta-HCG) and pregnancy-associated plasma protein-A (PAPP-A, or PA). The proteins can be detected through a blood test. Abnormal levels of them have been associated with an increased risk of Down syndrome. These proteins aren't related to one another, so measurement of each reveals independent information. The result of one can confirm or cast doubt on the other.

These values, along with your age at delivery, yield an estimated risk of Down syndrome similar to that of the triple test. And they do so earlier because the triple test is given in the second trimester.

This test has a few limitations. The best time to measure free beta-HCG is after 12 weeks of gestation. PAPP-A begins to lose its testing accuracy after about 13 weeks. This leaves a small window of time to perform the tests. In addition, the length of the pregnancy must be known as accurately as possible to avoid error.

It's important to remember that these tests are screening tests. They can't uncover any actual problems or defects, only the risk of them. They aren't reliable screening tests for many other diseases. If results are normal, there still remains a chance that your baby will have a health problem. Even if the screening test results aren't normal, most babies will be healthy. This potential for false-negative and false-positive results may be a consideration in your decision about whether to be screened.

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