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The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy.

ABSTRACT: BACKGROUND:The imbalance between circulating concentrations of anti- and pro-angiogenic factors is usually intense in preeclampsia with severe features (sPE). It is possible that pre-delivery circulating levels of angiogenic factors in sPE may be associated with postpartum antihypertensive drug requirements. OBJECTIVE:To determine the predictive association between maternal pre-delivery serum concentrations of angiogenic factors and the use of ?3 slow- and/or a rapid-acting antihypertensive drug therapy in sPE on postpartum days zero to three following caesarean delivery. STUDY DESIGN:Women with sPE (n = 50) and normotensive pregnancies (n = 90) were recruited prior to childbirth. Serum samples were obtained from each participant < 48 hours before delivery to assess the concentrations of placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the Roche Elecsys platform. Each participant was followed up on postpartum days zero, one, two and three to monitor BP and confirm antihypertensive treatment. The optimal cut-off thresholds of sFlt-1/PIGF ratio from receiver operating characteristic curve predictive of the antihypertensive therapy were subjected to diagnostic accuracy assessment. RESULTS:The majority 58% (29/50) of sPE had multiple severe features of preeclampsia in the antenatal period with the commonest presentation being severe hypertension in 88% (44/50) of this group, followed by features of impending eclampsia which occurred in 42% (21/50). The median gestational age at delivery was 38 (Interquartile range, IQR 1) vs 36 (IQR 6) weeks, p < 0.001 in normotensive and sPE groups respectively. Notably, the median sFlt-1/PIGF ratio in normotensive and sPE groups were 7.3 (IQR 17.9) and 179.1 (IQR 271.2) respectively, p < 0.001. Of the 50 sPE participants, 34% (17/50) had early-onset preeclampsia. The median (IQR) of sFlt-1/PIGF in the early- and late-onset preeclampsia groups were 313.52 (502.25), and 166.59(195.37) respectively, p = 0.006. From postpartum days zero to three, 48% (24/50) of sPE received ? 3 slow- and/or a rapid-acting antihypertensive drug. However, the daily administration of ? 3 slow- and/or a rapid-acting antihypertensive drug in sPE were pre-delivery 26% (13/50), postpartum day zero 18% (9/50), postpartum day one 34% (17/50), postpartum day two 24% (12/50) and postpartum day three 20% (10/50). In sPE, the pre-delivery sFlt-1/PIGF ratio was predictive of administration of ?3 slow- and/or a rapid-acting antihypertensive drug on postpartum days zero, one and two with the optimal cut-off ratio being ?315.0, ?181.5 and ? 267.8 respectively (sensitivity 72.7-75.0%, specificity 64.7-78.6%, positive predictive value 40.0-50.0% and negative predictive value 84.6% - 94.3%). The predictive performance of sFlt-1/PIG ratio on postpartum day 3 among the sPE was not statistically significant (area under receiver operating characteristic curve, 0.6; 95% CI, 0.3-0.8). CONCLUSION:A pre-delivery sFlt-1/PIGF ratio (< 181.5) is a promising predictor for excluding the need for ?3 slow- and/or a rapid-acting antihypertensive drug therapy in the immediate postpartum period in sPE.

SUBMITTER: Ngene NC

PROVIDER: S-EPMC6485032 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy.

Ngene Nnabuike Chibuoke NC Moodley Jagidesa J Naicker Thajasvarie T

PloS one 20190425 4

<h4>Background</h4>The imbalance between circulating concentrations of anti- and pro-angiogenic factors is usually intense in preeclampsia with severe features (sPE). It is possible that pre-delivery circulating levels of angiogenic factors in sPE may be associated with postpartum antihypertensive drug requirements.<h4>Objective</h4>To determine the predictive association between maternal pre-delivery serum concentrations of angiogenic factors and the use of ≥3 slow- and/or a rapid-acting antihy ...[more]

PMID: 31022243

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Project description:Objective: To determine blood pressure (BP) patterns in the immediate postpartum period in preeclampsia with severe features (sPE) and normotensive pregnant women who had cesarean deliveries (CD).Study design: The BP levels of two groups comprising 50 sPE and 90 normotensive pregnant women who had CD were measured before delivery and on days 0-3 postpartum at four time points (05:00, 08:00, 14:00, and 22:00). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PIGF) were measured in the maternal serum ≤48 h before delivery.Results: Antihypertensive therapy was administered to 98, 96, 82, 78, and 56% of sPE antepartum and on postpartum days 0-3, respectively. De novo postpartum hypertension (BP ≥ 140/90 mmHg) occurred in 24.4% (22/90) of the normotensive group but only one required antihypertensive therapy. The occurrence of de novo postpartum hypertension was associated with maternal weight before delivery ≥ 84.5 kg (relative risks (RR) 2.6, CI 95% 1.2-5.8, p = .017), and body mass index before delivery ≥ 33.3 kg/m2 (RR 2.9, CI 95% 1.3-6.4, p = .008). In sPE, the BP decreased between predelivery period and postpartum day 0. From days 1 to 3 postpartum, there was a continuous increase in the daily mean BPs in both groups, with average daily increments (systolic/diastolic) being 5.6/4.6 mmHg and 0.6/1.3 mmHg in the sPE and normotensive women, respectively. Patient's group and time had a significant effect on BP, p < .001. Overall, daily mean BPs were higher in the sPE than the normotensive group (p < .001). Perceived stress (p = .022), low birth weight (p = .002), 5 min Apgar score ≤ 6 (p < .001) were significantly higher in the sPE group. sFlt-1/PIGF ratio was high in the hypertensive groups: sPE versus normotensive group, p < .001; de novo postpartum hypertension versus normotensives group that remained normotensive, p = .102.Conclusion: Postpartum BP and antihypertensive requirements are important considerations in managing sPE and normotensive pregnancies. sPE is associated with increased maternal stress and poor perinatal outcomes.

Project description:Placental dysfunction underlies a spectrum of perinatal pathologies, including preeclampsia and fetal growth restriction. Angiogenesis-related factors, including sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor), play an important role in placental dysfunction; altered levels are detectable several weeks before onset of pregnancy complications. In vitro diagnostic tests for these biomarkers can improve early diagnosis and facilitate prediction of maternal and fetal outcomes. We assessed evidence for combining angiogenic biomarkers with other biomarkers or clinical parameters to predict maternal/fetal outcomes in pregnant women with placental dysfunction. Pooled information on placental perfusion (ultrasonography, mean arterial pressure), clinical characteristics, and biomarker levels (PlGF) can improve first-trimester prediction and preeclampsia diagnosis. Angiogenic factors (sFlt-1/PlGF ratio; PlGF alone) with or without clinical characteristics can facilitate second-/third-trimester prediction of early-onset and late-onset preeclampsia. A combination of increased sFlt-1/PlGF ratio and ultrasound can rule out early fetal growth restriction. The sFlt-1/PlGF ratio is also a reliable tool for discriminating between pregnancy-related hypertensive disorders, including superimposed preeclampsia and gestational hypertension. Analysis of angiogenic factors with or without uterine Doppler substantially improves sensitivity and specificity for predicting adverse outcomes and iatrogenic preterm delivery. We propose to extend the American College of Obstetricians and Gynecologists definition of preeclampsia in the future to include the combination of new-onset hypertension and new-onset of altered angiogenic factors (sFlt-1/PlGF ratio or PlGF alone). In summary, altered angiogenic biomarkers indicate placental dysfunction, and their implementation into clinical practice will help reduce the considerable burden of morbidity and mortality associated with adverse pregnancy outcomes as a consequence of angiogenic-placental syndrome.

Project description:OBJECTIVE:Changes in the maternal plasma concentrations of angiogenic (placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. METHODS:This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of <0.05 was considered significant. RESULTS:(1) The prevalence of preeclampsia, term, preterm, (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. CONCLUSIONS:(1) The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGF/sEng.

Project description:BACKGROUND:Preeclampsia and preterm delivery (PTD) are believed to affect women's long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population. METHODS:This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing. RESULTS:A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P?<?1.3?×?10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia. CONCLUSION:In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women's future cardiometabolic health.

Dataset Information

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy.

Publications

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy.

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