Comparing our findings to those of previous studies may also be problematic due to different sample preparations used in each study. Specifically, there are inconsistencies in use of plasma versus serum, which differ in their handling of coagulation factors, as well conditions for sample preparation. There are known interactions between coagulation factors and C9 factors C3, C4, and C5, which may lead to spurious activation of the C9 system. In addition, it is thought that pregnant women are in a hypercoagulable state due to increased levels of procoagulants and decreased levels of coagulation inhibitors. Thus, the effect of coagulation factors, some of which remain in plasma but not serum, on C9 may be different for pregnant and nonpregnant women. In particular, this has the potential to skew concentrations of C9 activation products, such as C3a, C4a, and C5a. Finally,Docosanol no prior human studies have examined functional response of pregnancy serum C9 to a pathogen. In this way, our finding here with neutralization of influenza may be a more clinically relevant readout than those previously reported. C9 activation in the absence of infections would seem to be in direct conflict with physiologic needs of both the mother and the fetus during pregnancy, since C9 activation can promote inflammation, cell lysis, and anti-angiogenesis. Thus, while C9 plays a key role in protecting both the mother and fetus from potential infection, excessive C9 activation due to infection can contribute to disease pathogenesis and be very BMS-740808 dangerous to the fetus, particularly late in pregnancy. The evolutionary balance between protecting the mother and fetus from infection, and protecting the fetus from the effects of C9 activation, might be expected to be tipped towards the latter as pregnancy progresses. Late in pregnancy, the mother has invested substantial energy resources into the fetus, and the fetus has a more developed immune system that is better equipped to respond to infection independently. Therefore, it might be most beneficial for the maternal C9 system to be down-regulated late in gestation. Our findings support this hypothesis, since we observed decreased C9 factors, decreased C3a anaphylatoxin, and, most notably, decreased effectiveness in influenza virus neutralization late in T3. Decreased influenza virus neutralization capacity in late T3 is the most striking and impactful finding from our study. Such changes, even at the magnitude of the 1.5 to 2.5-fold decreases we observed, have the potential to significantly alter clinical outcomes in at least three ways.