Low placental growth factor across pregnancy identifies a subset of women with preterm preeclampsia: type 1 versus type 2 preeclampsia?

Abstract

Preeclampsia is a heterogeneous syndrome affecting 3% to 5% of all pregnancies. An imbalance of the antiangiogenic and proangiogenic factors, soluble receptor fms-like tyrosine kinase 1 and placental growth factor (PGF), is thought to contribute to the pathophysiology of preeclampsia. Maternal plasma PGF and soluble receptor fms-like tyrosine kinase 1 were quantified by specific immunoassays in cross-sectional samples from 130 preeclamptic subjects and 342 normotensive controls at delivery and longitudinally in samples from 50 women who developed preeclampsia and 250 normotensive controls. Among women who developed preeclampsia, 46% (n=23) evidenced a pattern of consistently low maternal PGF across pregnancy below the lower 95% CI of controls from 15 weeks' gestation to term. In contrast, the remaining 54% (n=27) of women who developed preeclampsia had maternal PGF concentrations similar to or above (n=7) those of normotensive controls. Subjects with low PGF across pregnancy who developed preeclampsia evidenced significantly higher blood pressure in early pregnancy (P<0.05) and, after diagnosis, earlier gestational age at delivery (P<0.05) and more preterm birth (P<0.05) compared with preeclamptic patients with high PGF. A significant subset of women who develop preeclampsia show evidence of consistently low PGF across pregnancy. Low PGF with preeclampsia was associated with preterm delivery compared with preeclamptic patients with high PGF. Identifying women with consistently low plasma PGF during pregnancy may provide a greater understanding of preeclampsia pathophysiology and may provide more focused research and clinical activities.

Figure 1. Box and whisker plots of maternal plasma PGF (A) and maternal plasma sFLT1 (B) at delivery

The filled black circles are the median, the open circles are the 90th and 10th percentiles, and the top and bottom lines of the box are the 75^th and 25^th percentiles of the data for each group. Statistical significance is indicated by p values.

Figure 2. Box and whisker plots of maternal plasma PGF (A, C) and maternal plasma sFLT1 (B, D) across gestation (A, B) or by clinical onset of preeclampsia with gestational age matched control samples (C, D)

Open boxes are controls and shaded boxes are subjects who developed preeclampsia. The number above each box indicates the number of samples. The filled black circles are the median, the open circles are the 90th and 10th percentiles, and the top and bottom lines of the box are the 75^th and 25^th percentiles of the data for each group. Statistical significance is indicated by p values.

Figure 3. Median ± 95% CI of plasma PGF concentrations (A, B) and sFLT1 concentrations (C, D) from 10 to 40 weeks gestation

Women with uncomplicated pregnancies (solid black line), women who developed preeclampsia and had plasma PGF concentrations within the 95%CI of control uncomplicated pregnant women (dashed blue line, A & C), and women who developed preeclampsia and had plasma PGF concentrations below the 95%CI of control uncomplicated pregnant women from 15 weeks gestation to delivery (solid red line, B & D).