Precursors to pre-eclampsia: are there markers in the fetal circulation?

One of the fundamental issues in pre-eclampsia (hypertension in pregnancy) research is to find serum proteins that can act as markers of disease predisposition, remote disease onset, imminent disease onset or disease activity at the height of its destructive powers. We make assumptions, not infrequently, that positive findings at the time of delivery reflect early changes in the maternal and fetal circulations. Very little has been defined in terms of fetal circulation, as it is, by and large, deemed to be harder to access and less likely to lend itself to useful non-invasive diagnostic tests in early pregnancy. The study published in this issue of Clinical Science by Prickett et al. shows that there is a differential expression of the precursor molecule of CNP (C-type natriuretic peptide), N-terminal proCNP, in pre-eclampsia. At term, pre-eclamptic umbilical cord plasma concentrations are decreased relative to normal pregnancy, possibly reflecting a decrease in placental production. At the same time maternal levels are increased relative to normal pregnancies and this possibly reflects an increase in myometrial/endovascular production. There is no doubt that the predominant actions of these hormones are local and whether plasma levels are a true reflection of dynamic changes in local production and effect is yet to be seen. This study represents a promising start in identifying large stable molecules which could be markers for pre-eclampsia. This study has relatively small numbers of patients and work still needs to be done to determine the utility of umbilical cord levels in early phases of the disease. Whether serum levels of N-terminal proCNP can provide an accurate reflection of normal or pathological maternal uterine adaptation to pregnancy remains a question worth evaluating.