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. © 1997 by John Wiley & Sons, Ltd.

Inclusion of serum marker measurements from a previous pregnancy improves Down syndrome screening performance

“…Spencer (1997) found an average value of 29·0 for his second pregnancies, a value that may be lower than in many other coutnries because of the relatively high frequency of teenage pregnancies in the U.K. It is not important to have an exact distribution, but it certainly should be reflected in the calculations that the women under consideration are somewhat older than the average pregnant population.…”

“…These values are assumed to be in agreement with general experience (Larsen et al, 1998). For the correlation between log MoM values from two normal pregnancies r=0·24 for AFP and r=0·37 for hCG were used in agreement with Spencer's results (Spencer, 1997), which however, are based on free beta hCG values. The same values were assumed for the correlation between results from a normal versus a Down syndrome pregnancy.…”

“…Furthermore, Dar et al (1996) published the values 0·33 for AFP and 0·30 for intact hCG. Recently Spencer (1997) reported the values 0·24 for AFP and 0·36 for free beta hCG based on a large material of almost 5000 women who had two or more normal singleton pregnancies during the period studied.…”

Maternal serum screening for trisomy 21 in women with a false positive result in last pregnancy

“…Holding and Cuckle (1994) reported a three-to fivefold risk, and Spencer (1997) also found a five-fold increased risk of a false positive test result. This is supported by the positive correlation between the paired MoM values between pregnancies.…”

“…Holding and Cuckle (1994) and Spencer (1997) also analysed their results in relation to maternal age. Both groups both found that women under the age of 35 had a higher chance of an abnormal result in the next pregnancy but they found was no effect in women of 35 years or more.…”