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1.
Niger J Clin Pract ; 27(5): 599-603, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38842709

ABSTRACT

BACKGROUND AND AIM: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia. MATERIALS AND METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters. RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively). CONCLUSION: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.


Subject(s)
Pre-Eclampsia , Humans , Female , Pregnancy , Adult , Pre-Eclampsia/blood , Pre-Eclampsia/physiopathology , Pre-Eclampsia/diagnosis , Case-Control Studies , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/physiopathology , Blood Coagulation/physiology , Severity of Illness Index , Young Adult , Fibrinogen/metabolism , Fibrinogen/analysis , Prothrombin Time , Mean Platelet Volume , Hemoglobins/analysis , Partial Thromboplastin Time
2.
JAMA Netw Open ; 7(6): e2416844, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38869897

ABSTRACT

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.


Subject(s)
Pre-Eclampsia , Humans , Female , Adult , Pregnancy , Pre-Eclampsia/diagnosis , Pre-Eclampsia/therapy , Early Diagnosis , Quality Improvement , Patient Readmission/statistics & numerical data , Postpartum Period , Hypertension/diagnosis , Hypertension/therapy , Infant, Newborn , Puerperal Disorders/therapy , Puerperal Disorders/diagnosis
3.
Rev Med Liege ; 79(5-6): 448-454, 2024 Jun.
Article in French | MEDLINE | ID: mdl-38869138

ABSTRACT

Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It complicates 2 to 8 % of pregnancies worldwide and represents the leading cause of maternal and fetal mortality in developed countries. The only definitive treatment remains termination of pregnancy and delivery of the placenta. Prompt assessment of maternal and fetal status should be held in search of severity criteria and adequate management of this condition according to gestational age. Foremost concerns for pregnant patients are impending eclampsia or placental abruption, while fetal complications arise from placental insufficiency and risks associated with premature pregnancy termination. The sole efficient prophylaxis of preeclampsia in current state of evidence is aspirin at a dosage of 160 mg per day in high risk patients. Preeclampsia is now recognized as a high-risk factor for cardiovascular, renal, and neurological diseases and should therefore be considered as an opportunity for screening and prevention.


La prééclampsie (PE) est un syndrome unique à la grossesse défini par une hypertension artérielle gravidique, associée à une protéinurie ou une atteinte d'organe après 20 semaines d'aménorrhée. Elle complique 2 à 8 % des grossesses à l'échelle mondiale, et représente la première cause de mortalité maternelle et fœtale dans les pays industrialisés. Le seul traitement curatif demeure l'arrêt de la grossesse et la délivrance du placenta. Cette pathologie justifie une évaluation rapide de l'état maternel et fœtal, afin de juger des critères de sévérité et d'orienter la prise en charge selon le terme de la grossesse. La menace maternelle est dominée par le risque de survenue d'une éclampsie ou d'un hématome rétroplacentaire alors que les complications fœtales découlent de l'insuffisance placentaire et des risques inhérents à un arrêt prématuré de grossesse. Le seul traitement préventif actuellement validé en prévention secondaire chez les patientes à haut risque est l'aspirine à une dose de 160 mg par jour. La PE est désormais reconnue comme un facteur de risque cardiovasculaire, rénal et neurologique, et doit être considérée, de ce fait, comme une opportunité de dépistage et de prévention.


Subject(s)
Pre-Eclampsia , Humans , Pregnancy , Pre-Eclampsia/prevention & control , Pre-Eclampsia/diagnosis , Female , Risk Factors
4.
Metabolomics ; 20(4): 65, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38879866

ABSTRACT

BACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.


Subject(s)
Biomarkers , Lipidomics , Lipids , Pre-Eclampsia , Humans , Pregnancy , Female , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Pre-Eclampsia/metabolism , Lipidomics/methods , Adult , Biomarkers/blood , Lipids/blood , Lipids/analysis , Tandem Mass Spectrometry , Lipid Metabolism , Chromatography, High Pressure Liquid , Gestational Age
5.
Int J Mol Sci ; 25(11)2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38892323

ABSTRACT

The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.


Subject(s)
Biomarkers , Placenta , Pregnancy Outcome , Pregnancy Trimester, First , Humans , Pregnancy , Female , Pregnancy Trimester, First/metabolism , Placenta/metabolism , Pre-Eclampsia/diagnosis , Pre-Eclampsia/metabolism , MicroRNAs/genetics , Pregnancy-Associated Plasma Protein-A/metabolism , Diabetes, Gestational/diagnosis , Diabetes, Gestational/metabolism
6.
Medicine (Baltimore) ; 103(25): e38557, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905404

ABSTRACT

Preeclampsia (PE) is a serious condition that threatens pregnancy with severe sequelae on both the mother and infant. Early detection of PE will lead to favorable outcomes, and using readily available markers like hematological indices is an attractive choice. Examine the diagnostic utility of hematological indices in pregnant women to predict preeclampsia and its severity. In a retrospective case-control study that included 252 women, all had their complete blood picture evaluated during their first and third trimesters as part of their outpatient antenatal care during their pregnancy. They were also divided into 3 groups: healthy pregnant women (control), non-severe PE, and severe PE, each involving 84 women. The changes in platelet to lymphocyte ratio (PLR) between 1st and 3rd trimesters showed an excellent ability to differentiate between severe PE and control (area under the curve = 0.954, cutoff ≤ -5.45%) and a good ability to differentiate between severe PE and non-severe PE (area under the curve = 0.841, cutoff ≤ -7.89%). Neutrophil to lymphocyte ratio showed a good to excellent ability to differentiate between severe PE and non-severe PE compared to control in the first and third trimesters and the percentage change between them. Changes in neutrophil to lymphocyte ratio and PLR strongly predict preeclampsia and its severity since they offer more predictive values than measuring NLP and PLR at different stages of pregnancy individually.


Subject(s)
Pre-Eclampsia , Severity of Illness Index , Humans , Female , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pregnancy , Retrospective Studies , Adult , Case-Control Studies , Lymphocyte Count , Platelet Count , Predictive Value of Tests , Biomarkers/blood , Lymphocytes , Neutrophils
7.
Am J Physiol Heart Circ Physiol ; 327(1): H89-H107, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38758122

ABSTRACT

The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 28 March, 2023) for RUPP studies in murine. Primary outcomes included maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump length, fetal reabsorptions, or antiangiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD = 24.1 mmHg; [22.6; 25.7]; n = 148), proteinuria (SMD = 2.3; [0.9; 3.8]; n = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2]; n = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4]; n = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34]; n = 113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Because of underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.


Subject(s)
Disease Models, Animal , Fetal Growth Retardation , Pre-Eclampsia , Uterus , Fetal Growth Retardation/physiopathology , Female , Pregnancy , Pre-Eclampsia/physiopathology , Pre-Eclampsia/diagnosis , Animals , Mice , Uterus/blood supply , Uterus/physiopathology , Blood Pressure , Vascular Endothelial Growth Factor Receptor-1/blood , Vascular Endothelial Growth Factor Receptor-1/metabolism , Fetal Weight
8.
Eur J Obstet Gynecol Reprod Biol ; 298: 53-60, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728842

ABSTRACT

OBJECTIVES: To evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. STUDY DESIGN: This case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. RESULTS: Urine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). CONCLUSIONS: Urinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.


Subject(s)
Biomarkers , Creatinine , Placenta Growth Factor , Pre-Eclampsia , Vascular Endothelial Growth Factor Receptor-1 , Humans , Female , Pregnancy , Pre-Eclampsia/urine , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Vascular Endothelial Growth Factor Receptor-1/urine , Placenta Growth Factor/blood , Placenta Growth Factor/urine , Adult , Biomarkers/urine , Biomarkers/blood , Case-Control Studies , Prospective Studies , Creatinine/urine , Creatinine/blood , Predictive Value of Tests , Longitudinal Studies
9.
Arch Gynecol Obstet ; 310(1): 315-325, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38734998

ABSTRACT

PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.


Subject(s)
Biomarkers , Chorionic Gonadotropin, beta Subunit, Human , Fetal Growth Retardation , Hypertension, Pregnancy-Induced , Pregnancy Trimester, First , Pregnancy, Twin , Pregnancy-Associated Plasma Protein-A , Premature Birth , Humans , Female , Pregnancy , Pregnancy, Twin/blood , Adult , Retrospective Studies , Pregnancy Trimester, First/blood , Biomarkers/blood , Fetal Growth Retardation/blood , Pregnancy-Associated Plasma Protein-A/analysis , Pregnancy-Associated Plasma Protein-A/metabolism , Premature Birth/blood , Premature Birth/epidemiology , Chorionic Gonadotropin, beta Subunit, Human/blood , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/epidemiology , Infant, Small for Gestational Age , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pre-Eclampsia/epidemiology , Pregnancy Outcome , Infant, Newborn , Cohort Studies , Portugal/epidemiology , Gestational Age
10.
Med J Aust ; 220(11): 582-591, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38763516

ABSTRACT

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.


Subject(s)
Hypertension, Pregnancy-Induced , Humans , Pregnancy , Female , Australia , New Zealand , Hypertension, Pregnancy-Induced/diagnosis , Hypertension, Pregnancy-Induced/therapy , Hypertension, Pregnancy-Induced/prevention & control , Pre-Eclampsia/diagnosis , Pre-Eclampsia/prevention & control , Pre-Eclampsia/therapy , Societies, Medical , Obstetrics/standards , Antihypertensive Agents/therapeutic use , Practice Guidelines as Topic
11.
Hypertension ; 81(7): 1550-1560, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38690656

ABSTRACT

BACKGROUND: Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. METHODS: We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. RESULTS: Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho (P=0.018); increased leptin (P=0.016) and leptin/adiponectin ratio (P=0.027), and increased extracellular vesicles positive for tissue factor (P=0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment (P=0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women (P=0.003). CONCLUSIONS: Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia.


Subject(s)
Biomarkers , Cellular Senescence , Pre-Eclampsia , Humans , Female , Pre-Eclampsia/epidemiology , Pre-Eclampsia/diagnosis , Pregnancy , Adult , Biomarkers/blood , Biomarkers/urine , Cellular Senescence/physiology , Aging , Klotho Proteins , Aging, Premature/epidemiology , Leptin/blood , Prospective Studies , Adiponectin/blood , Glucuronidase/blood
12.
Hypertension ; 81(7): 1574-1582, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38708601

ABSTRACT

BACKGROUND: Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women. METHODS: We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria. RESULTS: We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%. CONCLUSIONS: The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148.


Subject(s)
Pre-Eclampsia , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A , Humans , Female , Pregnancy , Pre-Eclampsia/diagnosis , Prospective Studies , Adult , Pregnancy-Associated Plasma Protein-A/analysis , Pregnancy-Associated Plasma Protein-A/metabolism , Parity , Placenta Growth Factor/blood , Biomarkers/blood , Uterine Artery/diagnostic imaging , Predictive Value of Tests , Sensitivity and Specificity
13.
Clin Perinatol ; 51(2): 391-409, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705648

ABSTRACT

The complexity of preterm birth (PTB), both spontaneous and medically indicated, and its various etiologies and associated risk factors pose a significant challenge for developing tools to accurately predict risk. This review focuses on the discovery of proteomics signatures that might be useful for predicting spontaneous PTB or preeclampsia, which often results in PTB. We describe methods for proteomics analyses, proteomics biomarker candidates that have so far been identified, obstacles for discovering biomarkers that are sufficiently accurate for clinical use, and the derivation of composite signatures including clinical parameters to increase predictive power.


Subject(s)
Biomarkers , Premature Birth , Proteomics , Humans , Female , Pregnancy , Biomarkers/metabolism , Pre-Eclampsia/diagnosis , Pre-Eclampsia/metabolism , Infant, Newborn , Predictive Value of Tests
14.
Postgrad Med ; 136(4): 468-473, 2024 May.
Article in English | MEDLINE | ID: mdl-38781027

ABSTRACT

INTRODUCTION: Predictive tests are needed to ensure the development and subsequent follow-up of pre-eclampsia, which is responsible for significant rates of morbidity and mortality during pregnancy. This study aimed to evaluate the predictive value of the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score for the severity of preeclampsia. METHODS: We retrospectively analyzed the data of women diagnosed with pre-eclampsia at our clinic from January 2019 to January 2023. The control group consisted of normotensive, healthy pregnant women. Women diagnosed with preeclampsia were further evaluated in two groups: those with severe features and those without severe features. The clinical and demographic data of the cases were evaluated. The HALP score was calculated using the first trimester blood parameters of the cases and compared between groups. RESULTS: The study included 229 patients with preeclampsia and 142 normotensive healthy controls. Of the patients with preeclampsia, 104 (28.1%) had severe features of the disease. The HALP score was significantly higher in the preeclampsia group with severe features than in the control group (6.18 ± 2.66 vs. 3.75 ± 1.86; p = 0.006). In multivariate logistic regression analysis, the HALP score (odds ratio: 2.02, 95% confidence interval: 1.10-3.32, p = 0.017) was found to be an independent indicator for preeclampsia with severe features. A HALP score of > 4.61 predicted the development of preeclampsia with severe features with a sensitivity of 74.5% and a specificity of 81.3%. CONCLUSION: We found a significant correlation between the HALP score and preeclampsia with severe features. The HALP score may be useful in predicting the severity of preeclampsia.


Subject(s)
Pre-Eclampsia , Severity of Illness Index , Humans , Female , Pregnancy , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Adult , Retrospective Studies , Predictive Value of Tests , Hemoglobins/analysis , Serum Albumin/analysis , Case-Control Studies , Platelet Count
15.
Clin Chim Acta ; 560: 119717, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38782157

ABSTRACT

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality, with limited effective clinical treatment options. Active metabolomics offers a promising approach to uncover metabolic changes in PE and identify potential biomarkers or therapeutic targets. This study performed untargeted metabolomics using LC-MS to compare serum samples from preeclampsia and normal pregnancies. METHODS: We performed untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to compare serum samples from PE patients and normal pregnancies. We analyzed the alterations in metabolites and conducted functional experiments to assess the effects of LysoPE(16:0) on trophoblast cell invasion and migration. Mechanistic studies were performed to explore the potential targeting of GSK-3ß by LysoPE(16:0). RESULTS: Our metabolomics analysis revealed significant alterations in several metabolites, including lysophosphatidylcholines and organic acids. Notably, LysoPE(16:0) was found to be downregulated in the serum of PE patients. Functional experiments demonstrated that LysoPE(16:0) could promote trophoblast cell invasion and migration. Mechanistic studies suggest that the protective effect of LysoPE(16:0) against PE might be mediated through the modulation of the GSK-3ß/ß-Catenin pathway, with LysoPE(16:0) potentially targeting the GSK-3ß protein. CONCLUSIONS: Our findings highlight the potential role of LysoPE(16:0) in the pathophysiology of PE and its ability to modulate the GSK-3ß/ß-Catenin pathway. These results provide new insights into the metabolic changes associated with PE and suggest that LysoPE(16:0) could serve as a promising biomarker or therapeutic target for the prevention and treatment of PE.


Subject(s)
Glycogen Synthase Kinase 3 beta , Metabolomics , Pre-Eclampsia , Humans , Pre-Eclampsia/blood , Pre-Eclampsia/metabolism , Pre-Eclampsia/diagnosis , Pre-Eclampsia/prevention & control , Female , Pregnancy , Glycogen Synthase Kinase 3 beta/metabolism , Adult , Trophoblasts/metabolism , Cell Movement , Chromatography, Liquid
16.
Open Heart ; 11(1)2024 May 23.
Article in English | MEDLINE | ID: mdl-38782544

ABSTRACT

BACKGROUND AND AIMS: Pre-eclampsia complicates 3-5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia. METHODS: In a registry-based case-cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother's birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases. RESULTS: Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls. CONCLUSION: Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.


Subject(s)
Pre-Eclampsia , Registries , Humans , Female , Pregnancy , Pre-Eclampsia/epidemiology , Pre-Eclampsia/diagnosis , Sweden/epidemiology , Adult , Risk Factors , Risk Assessment/methods , Pregnancy Complications, Cardiovascular/epidemiology , Incidence , Heart Failure/epidemiology , Heart Failure/diagnosis , Heart Failure/etiology , Follow-Up Studies , Case-Control Studies , Retrospective Studies
17.
Indian J Gastroenterol ; 43(2): 325-337, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38691240

ABSTRACT

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseases such as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.


Subject(s)
HELLP Syndrome , Liver Failure, Acute , Pregnancy Complications , Humans , Pregnancy , Female , Liver Failure, Acute/therapy , Liver Failure, Acute/etiology , Liver Failure, Acute/diagnosis , Pregnancy Complications/therapy , Pregnancy Complications/diagnosis , Pregnancy Complications/etiology , HELLP Syndrome/therapy , HELLP Syndrome/diagnosis , Fatty Liver/therapy , Fatty Liver/diagnosis , Fatty Liver/complications , Fatty Liver/etiology , Prognosis , Pre-Eclampsia/diagnosis , Pre-Eclampsia/therapy
18.
Hypertension ; 81(7): 1561-1573, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38708607

ABSTRACT

BACKGROUND: PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. METHODS: Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). RESULTS: A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. CONCLUSIONS: Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. REGISTRATION: URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.


Subject(s)
Placenta Growth Factor , Pre-Eclampsia , Humans , Female , Pregnancy , Placenta Growth Factor/blood , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Adult , Biomarkers/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Pregnancy Outcome , Infant, Newborn
19.
Medicine (Baltimore) ; 103(21): e38260, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788026

ABSTRACT

Preeclampsia (PE) is a pregnancy complication characterized by placental dysfunction. However, the relationship between maternal blood markers and PE is unclear. It is helpful to improve the diagnosis and treatment of PE using new biomarkers related to PE in the blood. Three PE-related microarray datasets were obtained from the Gene Expression Synthesis database. The limma software package was used to identify differentially expressed genes (DEGs) between PE and control groups. Least absolute shrinkage and selection operator regression, support vector machine, random forest, and multivariate logistic regression analyses were used to determine key diagnostic biomarkers, which were verified using clinical samples. Subsequently, functional enrichment analysis was performed. In addition, the datasets were combined for immune cell infiltration analysis and to determine their relationships with core diagnostic biomarkers. The diagnostic performance of key genes was evaluated using the receiver operating characteristic (ROC) curve, C-index, and GiViTi calibration band. Genes with potential clinical applications were evaluated using decision curve analysis (DCA). Seventeen DEGs were identified, and 6 key genes (FN1, MYADM, CA6, PADI4, SLC4A10, and PPP4R1L) were obtained using 3 types of machine learning methods and logistic regression. High diagnostic performance was found for PE through evaluation of the ROC, C-index, GiViti calibration band, and DCA. The 2 types of immune cells (M0 macrophages and activated mast cells) were significantly different between patients with PE and controls. All of these genes except SLC4A10 showed significant differences in expression levels between the 2 groups using quantitative reverse transcription-polymerase chain reaction. This model used 6 maternal blood markers to predict the occurrence of PE. The findings may stimulate ideas for the treatment and prevention of PE.


Subject(s)
Biomarkers , Computational Biology , Pre-Eclampsia , Humans , Female , Pre-Eclampsia/blood , Pre-Eclampsia/immunology , Pre-Eclampsia/diagnosis , Pre-Eclampsia/genetics , Pregnancy , Computational Biology/methods , Biomarkers/blood , ROC Curve , Adult , Gene Expression Profiling/methods
20.
Anal Chem ; 96(21): 8450-8457, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38728011

ABSTRACT

Accurate and quantitative detection of pre-eclampsia markers is crucial in reducing pregnancy mortality rates. This study introduces a novel approach utilizing a fluorescent biosensor by the immunosorbent atom transfer radical polymerization (immuno-ATRP) assay to detect the pre-eclampsia protein marker CD81. The critical step used in this sensor is the novel signal amplification strategy of fluorescein polymerization mediated by ferritin-enhanced controlled radical polymerization, which combines with a traditional enzyme-linked immunosorbent assay (ELISA) to further reduce the detection limit of the CD81 protein concentration. The fluorescence intensity was linear versus logarithmic CD81 protein concentration from 0.1 to 10,000 pg mL-1, and the detection limit was 0.067 pg mL-1. Surprisingly, in 30% normal human serum (NHS), the sensor can also detect target protein over 0.1-10,000 pg mL-1, with 0.083 pg mL-1 for the detection limit. Moreover, the proposed biosensor is designed to be cost-effective, making it accessible, particularly in resource-limited settings where expensive detection techniques may not be available. The affordability of this method enables widespread screening and monitoring of preeclampsia, ultimately benefiting many pregnant women by improving their healthcare outcomes. In short, developing of a low-cost and susceptible direct detection method for preeclampsia protein markers, such as CD81, through the use of the immuno-ATRP assay, has significant implications for reducing pregnancy mortality. This method holds promise for early detection, precise treatment, and improved management of preeclampsia, thereby contributing to better maternal and fetal health.


Subject(s)
Biomarkers , Biosensing Techniques , Polymerization , Humans , Female , Pregnancy , Biomarkers/analysis , Biomarkers/blood , Biosensing Techniques/methods , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Tetraspanin 28/analysis , Tetraspanin 28/metabolism , Immunosorbents/chemistry , Limit of Detection , Fluorescence , Enzyme-Linked Immunosorbent Assay , Eclampsia/diagnosis
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