Serum markers for pre-eclampsia: An update on the analytes to be determined in the first, second, and third trimester

Abstract

Summary Pre-eclampsia is a pregnancy-specific disorder which affects up to 10% of pregnancies and which contributes substantially to perinatal morbidity and mortality of both mother and newborn. Many molecules have been evaluated as potential serum markers for the presence and confirmation of the disease in the third trimester, and subsequently for its prediction in the second trimester. With the increasing sensitivities of the laboratory assays, these efforts are now focused to the first trimester. Impaired early trophoblast invasion is supposed to be at the origin of the events leading to pre-eclampsia, suggesting that it should be possible to detect abnormal levels of certain molecules or markers, in particular those related to trophoblastic activity, at the very early stages of pregnancy. The scope of this paper is to review, with data from the literature as well as from an in-house study, the usefulness of various maternal serum markers, with a special focus on those of placental origin, for the early prediction of pre-eclampsia occurring later during gestation. It remains difficult to predict late-onset pre-eclampsia in early pregnancy, and no “miracle” first trimester serum marker has so far been found to be specifically associated to this pathology. The use of formulae combining concentrations of a set of markers, which must be regulated independently from each other, may increase the detection rate. Elevated concentrations of Inhibin A, Activin A and soluble endoglin (sEng), or reduced levels of Placenta Growth Factor (PLGF), Pregnancy-associated Plasma Protein A (PAPP-A), or Placental Protein-13 (PP13) indicate, with high sensitivity but low specificity, an increased risk of a later occurring gestational pathology and should alert the clinician.