Tests for genetic and neural tube defects include gender determination, chromosome analysis, and measurement of -fetoprotein (AFP) and acetylcholinesterase levels. Determination of the gender of the fetus is indicated when sex-linked inherited disorders are suspected (e.g., hemophilia, Duchenne's muscular dystrophy). In such disorders, the abnormal gene is carried by women, although the disorder itself is inherited only by male offspring. Although no specific tests for these disorders are currently available, knowing the gender of the fetus may aid in deciding whether to continue the pregnancy. Some couples carrying these disorders, for example, choose to abort all male fetuses, even though some would have been normal.⁵

Determining the chromosomal makeup (karyotype) of the fetus may also assist in the prenatal diagnosis of disorders such as Down syndrome (trisomy 21) and Tay-Sachs disease. Karyotyping, especially when augmented by staining techniques, includes determination of the number of chromosomes as well as specific morphologic changes in the chromosomes that may indicate various genetic disorders. Karyotyping is performed by culturing fetal cells and then photographing individual chromosomes during the metaphase of mitosis.⁶ Among the disorders that can be detected are alterations in carbohydrate, lipid, and amino acid metabolism. Karyotyping can take from 2 to 4 weeks before results are available to the client. Specimens for chromosome analysis must be delivered promptly to the laboratory performing the test. If immediate culturing is not possible, the sample must be incubated at normal body temperature for no longer than 2 days.⁷

Neural tube and other anatomic defects in the fetus can be determined by measuring levels of AFP and acetylcholinesterase in amniotic fluid. In the embryo, the central nervous system develops from the neural tube, which begins to form at about 22 days of gestation. Failure of the neural tube to close properly can result in disorders such as anencephaly, spina bifida, and myelomeningocele. During gestation, the major fetal serum protein is AFP. Similar to albumin, this protein is manufactured in large quantities by the fetal liver until the 32nd week of gestation, with peak production occurring at 13 weeks (see Chapter 3 - Immunology and Immunologic Testing). With a severe neural tube defect, higher than normal amounts of AFP escape into the amniotic fluid as well as into the maternal circulation. Routine prenatal screening includes determination of the mother's serum AFP level at 13 to 16 weeks of pregnancy. Causes of elevated maternal AFP levels are listed in Table 10-1. If maternal levels are elevated on two samples obtained 1 week apart, an ultrasound is performed to determine gestational age and to check for twins or gross fetal anomalies.

If the ultrasound is normal, amniotic fluid samples are obtained and analyzed for AFP levels.^8,9 If AFP levels are elevated in amniotic fluid, the presence of acetylcholinesterase in the fluid can be determined to confirm the presence of a neural tube defect. Using electrophoretic methods, the isoenzyme of acetylcholinesterase, which originates in fetal spinal fluid, can also be demonstrated and is more specific to the diagnosis of neural tube defect.¹⁰

AFP and acetylcholinesterase may be falsely elevated if the sample is contaminated with fetal blood. The level of the fetal spinal fluid isoenzyme of acetylcholinesterase is not, however, so affected.