Maternal serum screening for aneuploidy and open fetal defects

The application of population-based maternal serum screening to prenatal diagnosis has been shown to be practical and is now wide-spread. It has been estimated that more than 40% of genetics programs in the United States that offer second trimester maternal serum screening now use at least one analyte in addition to AFP (Dr. George J. Knight, personal communication). The studies described here suggest that additional refinements in maternal serum screening are not only possible but inevitable. The use and interpretation of the analytes AFP, uE3, and hCG continue to be examined and expanded upon (Table 1). In the future, it seems logical that other analytes may be added or may replace one or more of these currently used markers. We have demonstrated that with AFP, uE3, and hCG, a separate protocol will identify a significant portion of trisomy 18 fetuses with a minimal increase in the number of amniocenteses performed. Other significant aneuploidies, including Turner syndrome and triploidy, will be identified in screening for Down syndrome and trisomy 18. Although separate screening protocols for the detection of Turner syndrome and triploidy would not be of practical value, their detection within a screening protocol for Down syndrome is an added benefit and increases the value of the screening markers. The use of first trimester screening is being investigated. Although earlier diagnosis is attractive, routine first trimester screening for aneuploidy would necessitate the creation of an entirely new protocol for the collection of maternal serum samples and their interpretation, as well as a second round of screening for open fetal defects during the early second trimester. In contrast, an advantage of the current protocols is that screening for both types of abnormalities is possible using the same serum sample. Although research may eventually demonstrate that first trimester screening is technically feasible, an evaluation of the logistics of such screening may show it to be impractical. Obstetric implications of elevations and decreases in the new serum markers have not yet been studied carefully. It is logical, however, that just as with abnormal AFP (not explainable on a genetic basis), extreme levels of uE3 and hCG may also be associated with particular obstetric problems. Information on such deviations in analyte levels is just beginning to emerge. Finally, the study of maternal serum markers may contribute to an understanding of placental function in the second trimester, and ultimately advance our understanding of the underlying pathophysiologies of various fetal chromosomal and morphologic defects.(ABSTRACT TRUNCATED AT 400 WORDS)