Low Placental Growth Factor Across Pregnancy Identifies a Subset of Women With Preterm Preeclampsia

Abstract

Preeclampsia is a heterogeneous syndrome affecting 3–5% of all pregnancies. An imbalance of the anti and pro-angiogenic factors, soluble receptor fms-like tyrosine kinase 1 (sFLT1) and placental growth factor (PGF), are thought to contribute to the pathophysiology of preeclampsia. Maternal plasma PGF and sFLT1 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) 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 to preeclamptic patients with high PGF. A significant subset of women who develop preeclampsia evidence consistently low PGF across pregnancy. Low PGF with preeclampsia was associated with preterm delivery compared to 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.

Retraction: Etiopathology of preeclampsia — Recent progress from the perspective of a poor/ischemic placenta

“…Perhaps these different patterns of PlGF indicate that half of the preeclampsia cases result from insufficient angiogenic signaling (low PlGF), whereas the other half result from insensitivity to angiogenic signaling (high PlGF) or are determined by a different pathogenic factor. 56) These findings suggest the possibility of at least two kinds of predisposing factors. One may lead to the overproduction of sFlt-1, such as multiple pregnancy, hydatidiform mole, trisomy 13, and first pregnancy.…”

“…The observation of low and high PlGF levels 56) and, similarly a high sFlt-1/PlGF ratio ≥ 85 (angiogenic preeclampsia) and a low sFlt-1/PlGF ratio < 85 (nonangiogenic preeclampsia), 57) across pregnancy among women who develop preeclampsia may be an important finding in relation to the pathophysiology and study of preeclampsia. Perhaps these different patterns of PlGF indicate that half of the preeclampsia cases result from insufficient angiogenic signaling (low PlGF), whereas the other half result from insensitivity to angiogenic signaling (high PlGF) or are determined by a different pathogenic factor.…”

Early Pregnancy Prediction of Preeclampsia in Nulliparous Women, Combining Clinical Risk and Biomarkers

“…(3) 2 (3) 3 (4) 0 (0) 185 (89) 7 (3) 5 (2) 4 (2) 8 (4) 4811 (90) 107 (2) 163 (3) 127 (2) 137 (3) (17) 25 (12) 738 (14) 0.51 Previous termination 8 (12) 20 (10) 569 (11) 0.85 Smoking status non smoker ceased smoking in pregnancy current smokers 53 (77) 8 (11.5) 8 (11.5) 159 (76) 31 (15) 19 (9) 4047 (76) 718 (13) 580 ( 7 (3) 71 (34) 69 (33) 62 (30) 393 (7) 2705 (51) 1481 (28) 766 (14) <0.001 Mean (SD) systolic blood pressure (mm Hg) 114 (12) 112 (10) 107 (10) <0.001…”

Redefining Preeclampsia Using Placenta-Derived Biomarkers

“…The hypothesis that PlGF will discriminate a placental or a maternal predominance in the genesis of preeclampsia was supported by a recent study of the relationship of PlGF across pregnancy to preeclampsia. 156 Fifty women with preeclampsia could be clearly subdivided into 2 groups. Approximately half of the preeclampsia cases had consistently low PlGF from the start of the second trimester, whereas the other half had normal or high PlGF until delivery, similar to that of normal pregnant women.…”