Placental Growth Factor and Soluble, Fms-Like Tyrosine Kinase-1 in Preeclampsia: A Case-Cohort (PEARL) Study.

OBJECTIVE: Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia. METHODS: We conducted a case-cohort study including low-risk nulliparous women recruited at 11-13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35-37 weeks) and late-onset (>37 weeks) preeclampsia. RESULTS: The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25-38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P < 0.05). We observed a significant difference between cases and controls, with a median ratio 100 times higher in early preeclampsia (P < 0.001), 13 times higher in intermediate preeclampsia (P < 0.001), but no significant difference between groups in late-onset preeclampsia with matched controls. CONCLUSION: PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.

Pathological investigation of placentas in preeclampsia (the PEARL study).

INTRODUCTION: Preeclampsia (PE), but mainly preterm PE, is associated with deep placentation disorders. We aimed to compare placental pathologies in pregnancies affected by term and preterm PE compared to normal pregnancies. METHODS: We performed a prospective case-cohort study. Low-risk nulliparous women were recruited in the first trimester and women who developed PE were recruited at diagnosis. Placental pathologies were reported according to the Amsterdam Placental Workshop Group Consensus Statement and were compared between cases and controls. PE cases stratified as term (≥37 weeks) and preterm PE (<37 weeks). Our primary outcome was maternal vascular malperfusion (MVM). RESULTS: Twenty-four women who developed preterm PE were compared to 10 women who developed term PE and 41 women without PE. Preterm PE (92%) was associated with more MVM than term PE (10%, p < 0.01) and controls (4%, p < 0.01), but the rate of MVM was similar between term PE and controls (p = 0.56). Preterm PE was also associated with more placental infarcts (65% vs. 20% vs. 15%); advanced villous maturation (91% vs. 30% vs. 1%); and hypoplastic villous maturation (70% vs. 10% vs. 3%); and moderate to severe decidual vasculopathy (56% vs. 10% vs. 3%) than term PE and controls (all p < 0.05). CONCLUSION: Most cases of preterm PE are associated with MVM, placental infarcts, advanced and/or hypoplastic villous maturation, and moderate to severe decidual vasculopathy, while it is infrequent in term PE and pregnancies without PE. Preterm and term preeclampsia have a different pathologic process that should be considered for their prevention and clinical management.