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Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia.

ABSTRACT: Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome.Women evaluated for suspected PE at a tertiary hospital (2009-2012) had pregnancy outcomes categorized as 'referent' or 'severe', based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered 'unclassified'. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes.Three hundred twenty-eight singleton pregnancies presented at ?34.0?weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5?:?1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2-58) and 15 (95% CI 5.8-40) fold, respectively.This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

SUBMITTER: Palomaki GE

PROVIDER: S-EPMC4409832 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia.

Palomaki Glenn E GE Haddow James E JE Haddow Hamish R M HR Salahuddin Saira S Geahchan Carl C Cerdeira Ana Sofia AS Verlohren Stefan S Perschel Frank H FH Horowitz Gary G Thadhani Ravi R Karumanchi S Ananth SA Rana Sarosh S

Prenatal diagnosis 20150204 4

<h4>Introduction</h4>Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome.<h4>Methods</h4>Women evaluated for suspected PE at a tertiary hospital (2009-2012) had pregnancy outcomes categorized as 'referent' or 'severe', based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were consi ...[more]

PMID: 25641027

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Project description:Background: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated. Objective: We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design: Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results: Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP, PAPPA2, INHA, FSTL3, FLT1, PHYHIP and ENG, were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p<.0001). Notably, LEP, FLT1 and PHYHIP were more highly upregulated in sPE placentas from parturient persons of African versus Asian ancestry. Genes associated with allograft rejection and adaptive immune response were selectively upregulated in placentas from African ancestry parturitions and not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturitions with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients of Asian and European ancestries with the highest IL3RA levels for their ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p=.0005). Conclusions: African ancestry parturitions are associated with higher placental upregulation of metabolism (LEP) and hypoxia/angiogenesis (FLT1) genes, and selective upregulation of allograft rejection/adaptive immune response genes, including IL3RA. High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.

Project description:To compare the clinical characteristics and outcomes of preeclamptic women presenting with a normal plasma angiogenic profile with those subjects who are characterized by an abnormal angiogenic profile.This was a secondary analysis of a prospective cohort study in women presenting to obstetrical triage at <37 weeks of gestation and diagnosed with preeclampsia within 2 weeks of enrollment and in whom angiogenic factors (sFlt1 and PlGF) measurements were available. Patients were divided into two groups based on their circulating levels of these factors described as a ratio; the sFlt1/PlGF ratio, non-angiogenic preeclampsia (sFlt1/PlGF ratio <85) and angiogenic preeclampsia (sFlt1/PlGF ratio ?85). The data are presented by sFlt1/PlGF category using median and quartile 1-quartile 3 for continuous variables and by frequency and sample sizes for categorical variables.In our cohort, the patients with non-angiogenic preeclampsia (N?=?46) were more obese [BMI: 35.2 (31.6, 38.7) versus 31.1 (28.0, 39.0), p?=?0.04], more likely to have preexisting diabetes (21.7% versus 2.0%, p?=?0.002) and presented at a later gestational age [35 (32, 37) versus 32 (29, 34) weeks, p?<?0.0001] as compared with women with angiogenic preeclampsia (N?=?51). Women with non-angiogenic preeclampsia had no serious adverse outcomes (elevated liver function tests/low platelets: 0% versus 23.5%, abruption: 0% versus 9.8%, pulmonary edema: 0% versus 3.9%, eclampsia: 0% versus 2.0 %, small for gestational age: 0% versus 17.7% and fetal/neonatal death: 0% versus 5.9%) as compared with women with angiogenic preeclampsia. The rate of preterm delivery <34 weeks was 8.7% in non-angiogenic preeclampsia compared with 64.7% in angiogenic preeclampsia (p?<?0.0001). Interestingly, delivery between 34 and 37 weeks and resource utilization (hospital admission days) were similar in the two groups.In contrast to the angiogenic form, the non-angiogenic form of preeclampsia is characterized by little to no risk of preeclampsia-related adverse outcomes, other than iatrogenic prematurity. Incorporation of angiogenic biomarkers in the evaluation of preeclampsia may allow accurate and early identification of severe disease.

Project description:BackgroundPre-eclampsia (PE) is one of the leading causes of maternal morbidity and mortality globally. Adequate knowledge about a disorder contributes greatly to its prevention, control and management. This study assessed the level of knowledge of PE and evaluated the factors associated with knowledge adequacy among pregnant women attending antenatal care at a University Hospital in Kumasi-Ghana.MethodsThis cross-sectional study was conducted at the University Hospital in Kumasi, Ghana. A validated closed-ended questionnaire was used to collect socio-demographic information and history of PE. Knowledge of PE was assessed based on a series of questions regarding the awareness, signs/symptoms, risk factors and complications of PE. Responses were scored percentage-wise and grouped into low (< 60%), moderate (60-80%) and high (80-100%). Knowledge score was then re-stratified into adequate (% score of ≥60%) and inadequate knowledge of PE (% score of < 60%).ResultsThe prevalence of inadequate and adequate knowledge of PE was 88.6% (mean score = 55.5 ± 4.3%) and 11.4% (mean score = 76.3 ± 5.9%), respectively. For participants with adequate knowledge of PE, 9.1% (mean score = 67.4 ± 6.9%) and 2.3% (mean score = 85.2 ± 5.1%) had moderate and high knowledge, respectively. Using univariate logistic regression models, being older (> 35 years old) [cOR = 3.09, 95%CI (0.88-10.88), p = 0.049] and having a higher level of education (> SHS education) [cOR = 4.45, 95%CI (2.18-9.10), p < 0.0001] were significantly associated with greater odds of having adequate knowledge of PE. After controlling for potential confounders in multivariate logistic regression analysis, we found higher level of education to be independently associated with adequate knowledge of PE [aOR = 2.87, 95%CI (1.31-6.30), p = 0.008].ConclusionThe knowledge of PE among pregnant women in Ghana is low. The prominent factor that facilitates adequacy of knowledge of PE is higher level of education.

Project description:Preeclampsia is a pregnancy-specific disorder defined by the new onset of hypertension and proteinuria after 20 weeks of gestation. Although its precise etiology is still unknown, there is evidence suggesting that it may be a consequence of impaired decidual and stromal cell function. Recently, a stem cell population derived from endometrial tissue and isolated from menstrual effluent called menstrual stem cells (MenSCs) has been identified. MenSCs exhibit important angiogenic and inflammatory properties that may contribute to both normal and pathological complications of implantation and placentation, including preeclampsia. We hypothesized that the angiogenic and inflammatory activity of MenSCs is altered in women who have a past history of preeclampsia and that this phenotype persists postpartum. The primary outcome measures were stromal progenitor cell formation, in vitro induction of endothelial tube formation, and release of proinflammatory cytokines. MenSCs obtained from women with a previous normal or preeclamptic pregnancy displayed similar phenotypic characteristics, tri-differentiation capacity, and proliferation. MenSCs derived from women who had preeclampsia on their previous pregnancy had reduced angiogenic capacity (~30% fewer junctions and nodes, p < 0.05) and stromal progenitor cell formation (<50% measured at a serial dilution of 1?:?10.000, p < 0.05) when compared to controls. In vitro, MenSCs obtained from patients with a history of preeclampsia expressed less endoglin and secreted less VEGF but more IL-6 than controls did. These data are consistent with the hypothesis that the angiogenic and inflammatory properties of MenSCs of women with a previous pregnancy complicated by preeclampsia have reduced angiogenic capacity and are more proinflammatory than those of MenSCs of women with a previous normal pregnancy. This altered phenotype of MenSCs observed following preeclampsia could either be present before the development of the pathology, predisposing the endometrial milieu to and consequently leading to limited vascular remodeling, or be a consequence of preeclampsia itself. The former may afford opportunity for targeted therapeutic intervention; the latter, a putative biomarker for future risk of pregnancy complications.

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Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia.

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Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia.

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