Two serum proteins could serve as crystal ball for preeclampsia

In normotensive women, increased serum concentrations of the angiogenic factor soluble fms-like tyrosine kinase 1 (sFlt-1) and decreased levels of free placental growth factor (PlGF) predict the development of preeclampsia in the last 2 months of pregnancy, according to a nested case­control study within the Calcium for Preeclampsia Prevention Trial.

Researchers measured the serum concentrations of the total sFlt-1, free PlGF, and free vascular endothelial growth factor (VEGF) throughout the pregnancies of 120 pairs of women. Within each pair, one had preeclampsia and one did not.

The study found that while the level of sFlt-1 increased and the level of PlGF decreased during the last 2 months of pregnancy in all the normotensive women, these changes occurred earlier and were more pronounced in the women who later developed preeclampsia. SFlt-1 levels began increasing steeply approximately 5 weeks before the onset of the condition, reaching a mean serum level of 4,382 pg per mL in the women with preeclampsia versus 1,643 pg per mL in the normotensive women.

Similarly, PlGF levels were significantly lower in the women who later developed preeclampsia than in the controls. Decreases began at 13 to 16 weeks' gestation, with the greatest decreases occurring during the same 5 weeks prior to the development of the condition as the increase in sFlt-1.

Changes in the levels of both factors were greater in women with preterm preeclampsia and in women with preeclampsia and a small-for-gestational-age infant.

The hypothesis, according to an editorial in the same issue of the New England Journal of Medicine, is that increased levels of sFlt-1 herald placental vascular insufficiency and other manifestations of preeclampsia "by antagonizing the angiogenic and vasodilatory effects of vascular endothelial growth factor and PlGF." While large, longitudinal studies are needed to determine clinically useful and predictive levels of both factors, the study brings us one step closer to a practical intervention for a condition that affects 3% to 5% of pregnancies in the US.

Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350:672-683.

Solomon CG, Seely EW. Preeclampsia--searching for the cause. N Engl J Med. 2004;350:641-642.