he positive-predictive value of an elevated MSAFP value is only 2 percent. Approximately 98 percent of pregnancies with an MSAFP level exceeding 2.5 MoM have an etiology other than a neural-tube defect. hus, counseling is indicated not only to inform the patient about the beneits and limitations of targeted sonography for the diagnosis of neural-tube defects but also to review the numerous other conditions. Some of these include fetal anomalies, placental abnormalities, and adverse outcomes associated with MSAFP level elevation (see Table 14-6). he likelihood of one of these abnormalities or of an adverse pregnancy outcome in the absence of a recognized abnormality rises in proportion to the AFP level. Adverse outcomes include fetal-growth restriction, preeclampsia, preterm birth, fetal demise, and stillbirth. More than 40 percent of pregnancies may be abnormal if the MSAFP level is greater than 7 MoM (Reichler, 1994).
Second-trimester elevation of either hCG or dimeric inhibin alpha levels also shows signiicant association with adverse pregnancy outcomes. he outcomes reported are similar to those associated with MSAFP level elevation. Moreover, the likelihood of adverse outcome is augmented when levels of several markers are elevated (Dugof, 2005).
Many of these complications are assumed to result from placental damage or dysfunction. However, the sensitivity and positive-predictive values of these markers are considered too low to be useful for screening or management. No speciic program of maternal or fetal surveillance has been found to favorably afect pregnancy outcomes (Dugof, 2010). At Parkland Hospital, prenatal care for these women is not altered unless a specific complication arises. Despite the extensive list of possible adverse outcomes, it is reassuring that most women with unexplained elevation of these analytes have normal outcomes.
Low Maternal Serum Estriol Level. A maternal serum estriol level less than 0.25 MoM has been associated with two uncommon but important conditions. he irst, Smith-Lemli-Opitz syndrome, is an autosomal recessive condition resulting from mutations in the 7 -dehydrocholesterol reductase gene. It is characterized by abnormalities of the central nervous system, heart, idney, and extremities; with ambiguous genitalia; and with fetal-growth restriction. For this reason, the Society for Maternal-Fetal Medicine has recommended that sonographic evaluation be performed if an unconjugated estriol level is <0.25 MoM (Dugof, 2010). If abnormalities are identified, an elevated amnionic luid 7 -dehydrocholesterol level can conirm the diagnosis.
he second condition is steroid suatase diciency, also known as X-linked ichthyosis. It is typically an isolated condition, but it may also occur in the setting of a contiguous gene deletion syndrome (Chap. 13, p. 260). In such cases, it may be associated with Kallmann syndrome, chondrodysplasia punctata, and/or mental retardation (Langlois, 2009). If the estriol level is <0.25 MoM and the fetus appears to be male, chromosomal microarray analysis or fluorescence in situ hybridization to assess the steroid sulfatase locus on the X-chromosome may be considered.
As shown in Table 14-4, if irst-trimester screening is combined with second-trimester screening, aneuploidy detection is signiicantly improved. Combined screening test options require coordination between the provider and laboratory. Specifically, if a second sample is required, it is obtained during the appropriate gestational age window, sent to the same laboratory, and linked to the first-trimester results. The irst-and secondtrimester components cannot be performed independently because if either component yields positive results, then providing accurate risk assessment would be problematic.