If the amnionic fluid AFP level was elevated, an assay for amnionic luid acetylcholinesterase was concurrently performed. his capitalized on the tendency of acetylcholinesterase to leak directly from exposed neural tissue into the amnionic luid. The presence of both analytes in the amnionic luid was considered diagnostic for neural-tube defects (American College of Obstetricians and Gynecologists, 2016a).
The overall sensitivity of amniocentesis to diagnose open neural-tube defects approximates 98 percent, with a false-positive rate of 0.4 percent (Milunsky, 2004). Importantly, other fetal abnormalities are associated with elevated amnionic fluid AFP levels and positive assay results for acetylcholinesterase. These include ventral wall defects, esophageal atresia, fetal teratoma, cloacal exstrophy, and skin abnormalities such as epidermolysis bullosa. hus, by current standards, these amnionic luid analytes would be considered ancillary screening tests, understanding that a positive result would prompt additional fetal imaging.
With current imaging technology, most neural-tube defects are detected with sonography, and targeted sonography is the diagnostic test of choice (Dashe, 2006). Pregnant women now have the option of neural-tube defect screening with either MSAFP or sonography (American College of Obstetricians and Gynecologists, 20 16c). Although level II is used as a synonym for targeted sonography, the former might best be removed from our lexicon. Namely, today's targeted sonography includes a much more comprehensive evaluation of fetal anatomy (Chap. 10, p. 187).
As MSAFP screening was being adopted, the designation «advanced maternal age" (AMA) became popular. A 1979 National Institutes of Health Consensus Development Conference recommended advising pregnant women who were 35 years and older about the possibility of amniocentesis for fetal karyotyping. he threshold was based on the greater risk for selected fetal chromosomal abnormalities with increasing maternal age and on the assumption that at that time, the loss rate attributable to amniocentesis was equivalent to the fetal Down syndrome risk at maternal age 35. Notaby, this is no longer the case, as discussed later (p. 293).
Serum aneuploidy screening soon became available for women who would be younger than 35 at delivery. In 1984, Merkatz and colleagues reported that MSAFP levels were lower in pregnancies with trisomies 21 and 18 at 15 to 21 weeks' gestation. Maternal age was incorporated into the calculation, such that a speciic risk could be assigned (DiMaio, 1987; New England Regional Geneties Group, 1989). The MSAFP screen detected approximately 25 percent of cases of fetal trisomy 21 when the threshold ratio for a positive result was set at 1 :270. This ratio relects the approximate second-trimester risk for Down syndrome at maternal age 35. This trisomy 21
FIGURE 14-1 Trends in the percentage of births to women aged 35 to 44 years. (Data from the Centers for Disease Control and Prevention, 201o5.) risk threshold and the associated 5-percent false-positive rate became standards that remain in use in some laboratories today.