Placental Growth Factor and Soluble FMS-like Tyrosine Kinase-1 in Early-Onset and Late-Onset Preeclampsia

Abstract

E arly-onset and late-onset preeclampsia differs somewhat in their aggressiveness, placentation, and risk of fetal growth retardation and probably should be considered as 2 different entities. Evidence suggests that the relationship between vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and their common receptor, soluble fms-like tyrosine kinase 1 (sFlt1) is important for controlling vasculogenesis, angiogenesis, and placental development during pregnancy. sFlt1 inhibits angiogenic activity by binding to and inactivating the proangiogenic factors VEGF-A and PlGF. Low levels of free VEGF-A and PlGF and elevated levels of sFlt1 precede the onset of clinical signs of preeclampsia by several weeks. This cross-sectional study was designed to estimate whether these changes were more pronounced in earlyonset versus late-onset preeclampsia.Preeclampsia was defined with the standard criteria. Early-onset preeclamptic women had the condition diagnosed at 24-32 weeks of gestation and who were delivered prematurely because of preeclampsia. Those with lateonset preeclampsia had the condition diagnosed at Z35week gestation. The 3 control groups included nonpregnant women being seen in a reproduction center for infertility who later became pregnant and delivered successfully (nonpregnant control), healthy women at 24 to 32 weeks of gestation (early controls), and healthy women delivering at 36 to 42 weeks of gestation (late controls). Only women with single pregnancies were included. Antihypertensive treatment was given in both groups with preeclampsia if the systolic and diastolic blood pressure rose above 170 or 110 mm Hg, respectively. Blood samples were analyzed for sFlt1, PlGF, and VEGF-A by enzymelinked immunosorbent assay kits. Comparisons between early controls and late controls were to early-onset and late-onset groups, respectively.Study groups were similar in maternal age and parity was similar between the pregnant groups. Gestation length was 13 days shorter for delivery for the late-onset preeclampsia group than for their controls. Body mass index was higher in the early-onset preeclamptic women compared with early controls. All women had normal blood pressure in the first trimester, but those who later had earlyonset preeclampsia had a mean initial diastolic pressure of 77 mm Hg compared with 69 mm Hg for their controls. Nonpregnant control women, late controls, early controls, early-onset, and late-onset preeclamptic women had sFlt1 levels of 48 pg/mL, 7827 pg/mL, 886 pg/mL, 37,700 pg/mL, and 26,106 pg/mL, respectively. The relative increase, compared with the respective control group, was 43 times greater in women with early-onset and 3 times greater than in women with late-onset preeclampsia. Median plasma levels of PGIF for the same groups, respectively, were 110 pg/mL, 221 pg/mL, 577 pg/mL, 27 pg/mL, and 48 pg/mL. Women in the early-onset group who had a small for gestational age infant had PGIF levels of 8.2 pg/ mL compared with 61 pg/mL for early-onset preeclampsia group with...

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

“…Moreover, the concentrations of these factors can be used to predict the outcome of the disease in patients presented to the obstetrical triage area [73,75,126,127]. However, the prognostic performance of these biomarkers evaluated in the mid-trimester for late-onset preeclampsia has been suboptimal [105,[128][129][130][131]. Recently, an elevated plasma concentration of sST2 was observed prior to and at the time of the diagnosis of preeclampsia in a case-control study [132].…”

Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia

“…Preeclampsia was defined as EOP when onset was before and LOP when onset was after 32 gestational weeks (5). For the clinical spectrum of preeclampsia, see table 1.…”

“…Preeclampsia can be divided into early onset (EOP) or late onset preeclampsia (LOP), depending on whether the onset of the syndrome was before or after completed gestational week 32, although 34 weeks is sometimes used (5). EOP is associated with low birth weight and underlying placental abnormality, while LOP may represent a syndrome with a mixture of conditions, ranging from mild preeclampsia with moderate placental affection to hypertensive conditions in pregnancy without placental dysfunction (6,7).…”

“…Although many studies have demonstrated the involvement of coagulation, inflammation and angiogenesis in the pathogenesis of preeclampsia, most of them have focused on only one of these aspects and studies have mostly been rather small (5,(8)(9)(10)(11)(12). The relative importance of these mechanisms and the correlation between them are thus not fully defined.…”

A Prospective Study of Placental Growth Factor Assay as a Novel Biomarker in Predicting Early-Onset Preeclampsia in High-Risk Patients

“…They have the potential to predict the onset of preeclampsia and increase the accuracy of a diagnosis when used in combination with traditional diagnostic markers. Early-onset preeclampsia is associated with greater changes in PlGF compared with late-onset preeclampsia and normal pregnancy [11][12][13].…”