Advent of Maternal Serum Markers for Down Syndrome Screening

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Abstract
Trisomy 21, or Down syndrome, is the most common serious autosomal chromsome aberration in which affected individuals survive beyond infancy. The association between advancing maternal age and increased risk of trisomy 21 is well known, and pregnant women older than 35 years at delivery are routinely offered invasive prenatal diagnostic testing. More recently, the use of maternal serum markers in the second trimester of pregnancy to predict the risk of trisomy 21 for women under the age of 35 has received intensive analysis. Maternal serum alpha-fetoprotein (MSAFP) was the first of these markers to be identified, and an inverse correlation between MSAFP level and risk of trisomy 21 was noted. A second marker, unconjugated estriol (uE3), has also been studied, and a correlation between low uE3 and trisomy 21 has been demonstrated, with a high level of correlation between AFP and uE sub 3. The addition of uE3 to the screening protocol has not consistently improved detection rates, possibly because of its high correlation with AFP. A strong association of human chorionic gonadotropin (hCG) and Down syndrome was reported. This analyte is the most sensitive one in use today, although controversy exists regarding the best form of the analyte to use for trisomy 21 prediction. Several groups of investigators advocate measurement of total hCG, while others feel that measurement of the free-beta subunit of the molecule offers greater detection ability. The maximum detection rate that has been reported is 80 percent with a 5 percent false-positive rate using a combination of MSAFP, free-beta hCG, and maternal age. Although other laboratories have not been able to achieve this level of detection, it has become clear that free-beta hCG plus AFP is at least as good as the triple combination of AFP, total hCG and uE3, if not superior.