Second-trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome

In a group of 26 524 control pregnancies and a group of 3728 pregnancies affected by one or more of the pregnancy complications of low birthweight, intra-uterine growth restriction (IUGR), preterm delivery and stillbirth, I have compared the relative risk of occurrence of these complications in pregnancies which had a raised maternal serum AFP (>2.0 MoM), raised maternal serum free beta-hCG (>2.0 MoM), low AFP (<0.5 MoM), low free beta-hCG (<0.5 MoM), combined raised AFP and free beta-hCG (>2.0 MoM), and in those with an increased Down syndrome risk (1 in 250 or greater). In the low birthweight group, only an increased AFP and decreased free beta-hCG showed significance with relative risks of 1.6 and 2.1. In the IUGR group, also only an increased AFP and decreased free beta-hCG showed significance with relative risks of 1.6 and 2.3. In the preterm delivery group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG showed significance with relative risks of 3.8, 1.8 and 6.2. In the stillbirth group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG showed significance with relative risks of 4.5, 2,4 and 7.2. An isolated raised free beta-hCG or an increased Down syndrome risk were not associated with an increased relative risk for any of the pregnancy complications investigated. However, apart from the six to seven-fold increased risk when both AFP and free beta-hCG are above 2.0 MoM, suggesting increased risk of preterm delivery or impending fetal death, the clinical utility of such significant differences is probably poor.