Currently, prenatal screening for Down syndrome (DS) is primarily performed using the serum triple or quadruple screens. However, due to the rather low sensitivity and high false-positive rates of these screening methods, there are ongoing efforts to develop better markers so to improve our ability to accurately detect DS during both the first and second trimesters of pregnancy.
In the early 1990s, it was discovered that the human chorionic gonadotropin (hCG) found in many patients with trophoblastic disease was unusual in that it was more heavily glycosylated at both the O- and N-linked sites. Further study of this hyperglycosylated hCG (HhCG) revealed that it was also found in the urine early in the first trimester of normal pregnancies, and that it was elevated throughout pregnancy in the urine of women carrying DS-affected fetuses. This latter finding led to an evaluation of this molecule as a potential marker for the prenatal diagnosis of DS. These subsequent studies have confirmed the potential of HhCG as such a marker, detecting as high as 80% of DS pregnancies at a 5% false-positive rate alone, and up to 94% of DS pregnancies at a 3% false-positive rate in combination with other serum and urine markers. Additionally, the combination of HhCG and ultrasound biometry may serve as an alternative to automatic amniocentesis in women who have an elevated risk of carrying a DS-affected fetus, such as those of advanced maternal age.
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