Between-pregnancy biological variability of maternal serum alpha-fetoprotein and free beta hCG: Implications for Down syndrome screening in subsequent pregnancies

Abstract

In women who have an increased Down syndrome risk in a first pregnancy there is a five-fold greater chance of also having an increased Down syndrome risk in a second subsequent pregnancy. Similarly, in women who have a high alpha-fetoprotein (AFP) level in the first pregnancy, suggesting an increased risk of a neural tube defect (NTD), there is also a five-fold greater chance of them also having a high result in a second subsequent pregnancy. Such a biological association of serum marker levels between pregnancies suggests that there are additional maternal or genetic factors influencing the levels of these serum markers, other than the physiological factors which in themselves are poorly understood. In theory, it is possible to correct for high/low marker results in a previous pregnancy and to do so, I estimate, would reduce the overall Down syndrome screening false-positive rate by about 0.2 per cent. There are insufficient data to make any prediction regarding the impact on detection rates. The small reduction in false-positive rate is unlikely to be a feature worth implementing in Down syndrome screening programmes.