Serum levels of macrophage colony stimulating, vascular endothelial, and placenta growth factor in relation to later clinical onset of pre-eclampsia and a small-for-gestational age birth

The multisystem disorder of pre-eclampsia (PE) becomes manifest in late gestation, but the pathology originates in early pregnancy by the deleterious action of placental substances to the maternal endothelial system. These factors were searched for in the attempt to identify, as early as possible, the pregnancies with an increased risk of developing pre-eclampsia. The literature is equivocal regarding the usefulness of various markers including vascular endothelial growth factor (VEGF) and macrophage colony-stimulating factor (M-CSF). Results are often confounded by a varying fraction of pregnancies affected by foetal growth restriction (FGR) amongst the case and control groups. In a nested case-control study we compared the serum levels of M-CSF, VEGF, and placenta growth factor (PLGF) in 23 pregnancies with subsequent mild PE without FGR and nine FGR pregnancies without PE with 40 matched controls at 17, 25, and 33 weeks of gestation cross-sectionally and longitudinally. VEGF levels were reduced in FGR but not in subsequently pre-eclamptic pregnancies at 17, 25, and 33 weeks. In contrast, PLGF was reduced in the PE but not in the FGR group. M-CSF did not differ between the three groups. Depending on which growth factor is found to be reduced, an early distinction can be made in terms of an increased risk for PE or FGR. Inconsistencies in the literature may reflect differences in PE disease severity between studies and the presence of a varying fraction of cases with FGR.