Angiogenic factors in superimposed preeclampsia: a longitudinal study of women with chronic hypertension during pregnancy.

Imbalances in circulating angiogenic factors contribute to the pathogenesis of preeclampsia. To characterize levels of angiogenic factors in pregnant women with chronic hypertension, we prospectively followed 109 women and measured soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor at 12, 20, 28, and 36 weeks' gestation and postpartum. Superimposed preeclampsia developed in 37 (34%) and was early onset (<34 weeks) in 9 and later onset (≥34 weeks) in 28. Circulating levels of sFlt1 and the ratio of sFlt1 to placental growth factor were higher before clinical diagnosis at 20 weeks' gestation in women who subsequently developed early onset preeclampsia between 28 and 34 weeks compared with levels in women who never developed preeclampsia (P=0.001) or who developed late-onset preeclampsia (P=0.001). Circulating levels of sFlt1, soluble endoglin, and the ratio of sFlt1:placental growth factor were also significantly higher, and placental growth factor levels were significantly lower at the time of clinical diagnosis of superimposed preeclampsia in women with either early or late-onset superimposed preeclampsia compared with levels at similar gestational ages in those with uncomplicated chronic hypertension. We conclude that alterations in angiogenic factors are detectable before and at the time of clinical diagnosis of early onset superimposed preeclampsia, whereas alterations were observed only at the time of diagnosis in women with late-onset superimposed preeclampsia. Longitudinal measurements of angiogenic factors may help anticipate early onset superimposed preeclampsia and facilitate diagnosis of superimposed preeclampsia in women with chronic hypertension.