Testing AlphaFetoprotein AFP in Blood
Another screening procedure requires only a small sample of the pregnant woman's blood, hence its consideration as a noninvasive technique. Blood sampling of the mother allows the measurement of certain chemicals that have passed from the fetus to the amniotic fluid and through the placenta into the mother's circulation. A screening test does not provide a definite diagnosis, it indicates an increased possibility that a condition is present. Maternal blood testing can screen for open neural tube developmental defects and genetic disorders including down syndrome or other trisomies. Abnormal values of these chemicals suggest that parents consider further testing for proof of a fetal defect. Alpha-fetoprotein (AFP) is a protein found in all fetuses.
When a fetus has unusual openings in the skin, such as characterize the open neural tube defects (NTD's) like spina bifida, the level of this protein in the amniotic fluid and in the mother's blood is unusually high. In these defects, which form early in gestation and result from a failure of the structures that become the brain and spinal cord to close properly, nervous system tissue is on the outside of the body. NTDs cause a variety of problems, from mild to severe . Maternal blood is tested between 15 and 20 weeks of pregnancy. The test is sometimes abbreviated as MSAFP, standing for maternal serum alpha-fetoprotein. The protein actually is measured in the serum or liquid portion of the mother's blood, separated in the laboratory from the solid substances in the blood, such as red and white blood cells.
There is no absolute amount of AFP in maternal blood that positively identifies NTD. The amount is reported as MoM-multiples the mean for the gestational age. This represents how far from the mean or average the measured value of AFP falls. The analysis takes into consideration other factors that influence AFP, including mother's weight, race, and whether she has diabetes mellitus or is carrying more than one fetus (if known). The cut off score that indicates risk is set to miss as few actual NTDs as possible, but the majority of fetuses whose mothers show an elevated value do not have the defect.
MSAFP will be accurate in showing a neural tube defect in 80 to 85 percent of fetuses who actually have the defect, but as many as 90 percent of fetuses whose AFP screening test shows an elevation will turn out to be normal. This is called a false positive result. An elevated AFP is reason for sonographic study of the fetus's central nervous system to look for a neural tube defect or other abnormality associated with an increased maternal AFP level.
As AFP normally increases each week between 15 and 20 weeks of pregnancy, an elevated AFP could be due to an error in dating the pregnancy, so that the gestational age is actually greater than that calculated by last menstrual period. This can be determined by a sonogram and the AFP value reinterpreted according to the revision in the gestational age. Multiple pregnancies can also cause an increase in the mother's AFP levels. Sonography is very accurate in confirming multiple gestation. Other fetal defects associated with elevated AFP and are demonstrable on sonogram include fetal death and defects in the formation of the fetal abdominal wall and umbilical cord.
Anencephaly, a neural tube defect in which the skull is absent, can be diagnosed definitely by sonogram, but other NTDs can be missed. At the other end of the spectrum, an unusually low concentration of AFP in maternal serum may be associated with a trisomy. This must be corroborated by amniocentesis, although sometimes a well-performed comprehensive sonogram can find anomalies that are strongly indicative of Down syndrome. The accuracy of such sonograms depends in large part on the experience of the person performing the test. Even a slight change in the placement of the transducer or probe may cause an error in findings.
A karyotype, or mapping of the chromosome pairs, is the only way to make a definitive diagnosis of Down syndrome. Low AFP levels may also signify a molar pregnancy, confirmable by ultrasound, or an overestimate of gestational age. If the gestational age is shown on sonogram to be less than calculated by last menstrual period, the AFP can be reassessed in the laboratory and may prove to be normal, rather than low. Recently, two other assessments have been added to the maternal blood screen.
These are beta hCG and unconjugated estriol. Beta hCG is a specific part of the pregnancy hormone, human chorionic gonadotropin, and estriol is one of the estrogens that normally increase in pregnancy. When all three are used, this is called the triple screen. These values may be high or low in some of the conditions already discussed and may help make the test more precise. For example, in a neural tube defect, while the MSAFP is unusually high, the unconjugated estriol may be normal or low and the beta hCG normal.
In a fetal death, the MSAFP is high while both other values will be low. In a multiple pregnancy, all three markers, as they are called, will be high. The table below shows the three values in various fetal problems. Abnormal results of either MSAFP alone or of the triple screen still only provide a suggestion of a disorder. Any abnormal result requires confirmation because maternal blood screening is non invasive, some experts have suggested that the triple screen be used instead of amniocentesis in women over the age of 35 to check for chromosomal anomalies.
Amniocentesis would be reserved for women whose blood screening showed the possibility of abnormality. Unfortunately, while this would pick up most of these anomalies, it would miss 10 to 15 percent of babies with Down syndrome and up to 40 percent of other anomalies. Amniocentesis picks up very close to 100 percent of these. Some experts urge that MSAFP or the triple screen be routinely utilized for the early detection of fetal central nervous system abnormalities in all pregnancies. In Scotland and Ireland, countries with very high rates of neural tube defects, there is little question that this screening is justified, but there is no agreement as to whether it should be applied to all women. The usual rate of occurrence of NTDs is approximately 1 in 1,000 pregnancies in the United States.
Women who have previously had infants with neural tube defects have only a slightly increased likelihood of having another such fetus. They are nevertheless usually screened for Alpha-fetoprotein. At the least, all pregnant women should be informed of the availability of the test. The Centers for Disease Control and Prevention recommend screening when it is performed with counseling and the availability of follow-up testing.
When MSAFP or the triple screen is offered routinely to all pregnant women, the disadvantages of its high false positive rate are an increase in invasive tests, anxiety in pregnant women and their partners, increased expense of maternity care, and a small number of complications due to the amniocenteses performed. Research is currently under way to assess markers that would identify increased risk for Down syndrome in the first trimester of pregnancy. Some of these might even be measurable in the mother's urine. This would not eliminate the need for second-trimester screening for neural tube defects, however.
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