Human chorionic gonadotropin (hCG) is a glycoprotein hormone (~37 kDa) composed of two noncovalently linked subunits – the α - and β‑chain (~15 and 22 kDa respectively). The protein is produced by trophoblast tissue and serves to maintain the corpus luteum during the early weeks of pregnancy. In addition, it also influences steroid production.
Naturally, hCG appears only in blood and urine of pregnant women. The concentration of hCG rises exponentially in the first trimester of pregnancy to peak around 9th week of gestation. Subsequently, the hormone level decreases between gestational weeks ~10‑16 to approximately one‑fifth of peak concentration and remains at this level until term. In non‑pregnant women, hCG can be produced by trophoblastic and non‑trophoblastic tumors and germ cell tumors with trophoblastic components.
The serum of pregnant women mainly contains intact hCG. However, minor fraction of α - and β‑subunits circulate in an unbound form. The proportion of free βhCG averages ~1 % compared to intact hCG. As a result of the protein degradation process, additional hCG variants can be detected in blood and urine (e.g. nicked hCG, nicked βhCG, β core fragment). However, only the intact hormone is biologically active.
It is now well established that the free βhCG concentration in serum is a reliable marker for fetal aneuploidy. In a number of studies it could be confirmed that, free βhCG in combination with serum pregnancy‑associated plasma protein A (PAPP‑A) and the sonografic determination of nuchal translucency (NT), is the serum marker of choice to identify women at an increased risk of carrying a fetus affected with Down syndrome during the first trimester (week 8‑14) of pregnancy. Using this marker combination, detection rates of up to 70 % (serum markers only) and 90 % (combined with NT) have been described at a false positive rate of 5 %.
Median maternal serum free βhCG levels in affected pregnancies are higher compared to the median of non affected pregnancies. Based on the maternal age, the risk for having a Down syndrome pregnancy can be calculated using a specific algorithm e.g. based on likelihood ratios.