Evaluation of the diagnostic value of the HALP score, uric acid value, and uric acid-creatinine ratio in preeclampsia.

OBJECTIVE: In this study, we aimed to evaluate the diagnostic value of the HALP score, serum uric acid value, and uric acid-creatinine ratio, which are inflammatory markers, in the diagnosis of preeclampsia (PE). MATERIALS AND METHODS: One hundred sixty-six pregnant women who met the inclusion and exclusion criteria were included in the study. They were divided into two groups: 81 pregnant women diagnosed with PE (PE group) and 85 pregnant women with healthy pregnancies (control group). Demographic and obstetric stories of the groups; weeks of pregnancy at diagnosis; hematological and biochemical parameters; hemoglobin, albumin, lymphocyte, and platelet (HALP) score and serum uric acid-creatinine ratio (sUA/sCr); and the results of the newborns were recorded and compared between groups. RESULTS: There was no significant difference between the groups in terms of age, gravidity, parity, and body mass index (P values = 0.533, 0.188, 0.085, 0.915, resp.). Mean gestational age, mean birth weight, 1st and 5th minute Apgar scores, and mean umbilical cord pH values were lower in the PE group compared to the control group (P values = 0.0001 for all). Percentage of NICU admissions was higher in the PE group (P = 0.0001). HALP score of the PE group was significantly lower than the control group (2.2 vs. 3.2; P = 0.0001). Uric acid and sUA/sCr ratios were significantly higher in the PE group compared to the control group (for uric acid, 6.2 ± 1.7 vs. 4.5 ± 1.2; P = 0.0001; for sUA/sCr, 12.0 ± 4.0 vs. 9.9 ± 3.1; P = 0.0001). In diagnosing PE, serum uric acid had a sensitivity of 82.7% at values of 4.7 and above, 58% sensitivity at values of sUA/sCr ratio of 10.9 and above, and 3.7% sensitivity at HALP score values of 6.6 and above (P values = 0.0001, 0.001, 0.001, resp.). CONCLUSION: In our study, we found that the HALP score in PE was significantly lower than in healthy controls, and the uric acid value and sUA/sCr ratios were significantly higher. Diagnostic value of the serum uric acid value and then the sUA/sCr ratio were higher in PE. However, we found that the HALP score was insufficient for diagnosing PE.

Circulating extracellular vesicular microRNA signatures in early gestation show an association with subsequent clinical features of pre-eclampsia.

In a prospective cohort of subjects who subsequently developed preeclampsia (PE, n = 14) versus remaining healthy (NORM, n = 12), early gestation circulating extracellular vesicles (EVs) containing a panel of microRNA signatures were characterized and their biological networks of targets deciphered. Multiple microRNAs of which some arose from the placenta (19MC and 14MC) demonstrated changes in association with advancing gestation, while others expressed were pathognomonic of the subsequent development of characteristic clinical features of PE which set in as a late-onset subtype. This panel of miRNAs demonstrated a predictability with an area under the curve of 0.96 using leave-one-out cross-validation training in a logistic regression model with elastic-net regularization and precautions against overfitting. In addition, this panel of miRNAs, some of which were previously detected in either placental tissue or as maternal cell-free non-coding transcripts, lent further validation to our EV studies and the observed association with PE. Further, the identified biological networks of targets of these detected miRNAs revealed biological functions related to vascular remodeling, cellular proliferation, growth, VEGF, EGF and the PIP3/Akt signaling pathways, all mediating key cellular functions. We conclude that we have demonstrated a proof-of-principle by detecting a panel of EV packaged miRNAs in the maternal circulation early in gestation with possibilities of biological function in the placenta and other maternal tissues, along with the probability of predicting the subsequent clinical appearance of PE, particularly the late-onset subtype.

DNA methylation landscape in pregnancy-induced hypertension: progress and challenges.

Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.

Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction.

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction. Maternal plasma samples were collected from two independent cohorts: (1) Established disease cohort: 50 participants diagnosed with early-onset preeclampsia (< 34 weeks' gestation), 14 with early-onset fetal growth restriction, and 25 gestation-matched controls. (2) Prospective cohort, collected at 36 weeks' gestation before diagnosis: 17 participants later developed preeclampsia, 49 delivered infants with fetal growth restriction (birthweight < 5th centile), and 72 randomly selected controls. Metabolic evaluation was performed by Metabolomics Australia on the Agilent 6545 QTOF Mass Spectrometer. In the established disease cohort, 77 metabolites were altered in circulation from participants with preeclampsia - increased L-cysteine (3.73-fold), L-cystine (3.28-fold), L-acetylcarnitine (2.57-fold), and carnitine (1.53-fold) (p < 0.05). There were 53 metabolites dysregulated in participants who delivered a fetal growth restriction infant-including increased levulinic acid, citric acid (1.93-fold), and creatine (1.14-fold) (p < 0.05). In the prospective cohort, 30 metabolites were altered in participants who later developed preeclampsia at term - reduced glutaric acid (0.85-fold), porphobilinogen (0.77-fold) and amininohippuric acid (0.82-fold) (p < 0.05) was observed. There were 5 metabolites altered in participants who later delivered a fetal growth restriction infant - including reduced 3-methoxybenzenepropanoic acid (p < 0.05). Downstream pathway analysis revealed aminoacyl-tRNA biosynthesis to be most significantly altered in the established cohort in preeclampsia (13/48 hits, p < 0.001) and fetal growth restriction (7/48 hits, p < 0.001). The predictive cohort showed no significant pathway alterations. This study observed altered metabolites in maternal plasma collected before and after diagnosis of a preeclampsia or fetal growth restriction. While a significant number of metabolites were altered with established disease, few changes were observed in the predictive cohort. Thus, metabolites measured in this study may not be useful as predictors of preeclampsia or fetal growth restriction.

Diagnostic Accuracy of Serum Glycosylated Fibronectin in Prediction of Preeclampsia: A Nested Case-Control Study.

BACKGROUND: Preeclampsia is a life-threatening complication of pregnancy that occurs in approximately 7% of all pregnancies. In India, the incidence of preeclampsia is 8%-10% and the prevalence is 5.4%, whereas the prevalence of hypertensive disorders of pregnancy is 7.8%. AIM AND OBJECTIVES: This study was aimed at evaluating the diagnostic accuracy of serum glycosylated fibronectin (S. GlyFn) in the prediction of preeclampsia. METHODS: A nested case-control study was carried out for 16 months in the department of obstetrics and gynecology. A total of 240 women were recruited and followed after written consent and ethical clearance. Six were lost to follow-up, 15 had second-trimester abortions (excluded from the study), and 32 women developed hypertensive disorders of pregnancy (cases), out of which 1 woman developed antepartum eclampsia, 10 women developed preeclampsia with severe features, and 21 women developed preeclampsia without severe features. One hundred and eighty-seven women remained normotensive throughout the pregnancy until 6 weeks postpartum. After randomization, out of these samples, 54 were analyzed and considered controls. Levels of S. GlyFn were estimated using an ELISA kit using the ELISA technique. RESULTS: The mean S. GlyFn level was significantly higher at the time of enrollment among those women who later developed preeclampsia (127.59 ± 27.68 ng/m) as compared to controls (107.79-53.51 ng/mL). GlyFn at a cutoff value of 126.70 ng/mL significantly (P = 0.034) discriminates cases of preeclampsia with severe features from healthy controls with a sensitivity of 90.00%, a specificity of 63.00%, a 31.03% positive predictive value, and 97.14% negative predictive value. CONCLUSION: S. GlyFn, at a cutoff value of 126.70 ng/mL, had good sensitivity to discriminate PE from normotensive and was also a good prognostic marker.

Résumé Contexte:La prééclampsie est une complication potentiellement mortelle de la grossesse qui survient dans environ 7 % de toutes les grossesses. En Inde, l'incidence de la prééclampsie est de 8 % à 10 % et la prévalence est de 5,4 %, alors que la prévalence des troubles hypertensifs de la grossesse est 7,8 %. But et objectifs : Cette étude visait à évaluer la précision diagnostique de la fibronectine sérique glycosylée (S. GlyFn) chez la prédiction de la prééclampsie.Méthodes:Une étude cas-témoin nichée a été menée pendant 16 mois dans le service d'obstétrique et gynécologie. Au total, 240 femmes ont été recrutées et suivies après consentement écrit et autorisation éthique. Six ont été perdus de vue, 15 avaient avortements au deuxième trimestre (exclus de l'étude), et 32 femmes ont développé des troubles hypertensifs de la grossesse (cas), dont 1 femme a développé une éclampsie antepartum, 10 femmes ont développé une prééclampsie avec des caractéristiques sévères et 21 femmes ont développé une prééclampsie sans traits sévères. Cent quatre-vingt sept femmes sont restées normotendues tout au long de la grossesse jusqu'à 6 semaines après l'accouchement. Après randomisation, sur ces échantillons, 54 ont été analysés et considérés comme témoins. Les niveaux de S. GlyFn ont été estimés à l'aide d'un kit ELISA en utilisant la technique ELISA.Résultats:Le niveau moyen de S. GlyFn était significativement plus élevé au moment de l'inscription chez les femmes qui ont développé plus tard une prééclampsie (127,59 ± 27,68 ng/m) par rapport aux témoins (107,79­53,51 ng/mL). GlyFn à une valeur seuil de 126,70 ng/mL de manière significative (P = 0,034) discrimine les cas de prééclampsie avec des caractéristiques sévères des témoins sains avec une sensibilité de 90,00 %, un spécificité de 63,00 %, une valeur prédictive positive de 31,03 % et une valeur prédictive négative de 97,14 %.Conclusion:S. GlyFn, à une valeur seuil de 126,70 ng/mL, avait une bonne sensibilité pour distinguer l'EP du normotendu et était également un bon marqueur pronostique.

Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities.

The complement system (C) is a crucial component of the innate immune system. An increasing body of research has progressively shed light on the pivotal role of C in immunological tolerance at the feto-maternal interface. Excessive C activation or impaired C regulation may determine the onset of pregnancy-related pathological conditions, including pre-eclampsia (PE). Thus, several studies have investigated the presence of C components or split products in blood matrixes (i.e., plasma, serum), urine, and amniotic fluid in PE. In the current study, we systematically reviewed the currently available scientific literature reporting measurements of C components as circulating biomarkers in PE, based on a literature search using Pubmed, Scopus, and Embase databases. A total of 41 out of 456 studies were selected after full-text analysis. Fourteen studies (34.1%) were identified as measuring the blood concentrations of the classical pathway, 5 (12.1%) for the lectin pathway, 28 (68.3%) for the alternative pathway, 17 (41.5%) for the terminal pathway components, and 16 (39%) for C regulators. Retrieved results consistently reported C4, C3, and factor H reduction, and increased circulating levels of C4d, Bb, factor D, C3a, C5a, and C5b-9 in PE compared to normal pregnancies, depicting an overall scenario of excessive C activation and aberrant C regulation. With evidence of C activation and dysregulation, C-targeted therapy is an intriguing perspective in PE management. Moreover, we also discussed emerging pitfalls in C analysis, mainly due to a lack of experimental uniformity and biased cohort selection among different studies and laboratories, aiming to raise a more comprehensive awareness for future standardization. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024503070.

[Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues]. / 产科抗磷脂综合征的诊治原则与热点问题述评.

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

Adiponectin and leptin profiles among obese pregnant women with preeclampsia vs. non-preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: Preeclampsia (PE) affects only about 10% of women who meet the criteria for obesity based on their body mass index (BMI). Obesity is suggested to play a role in preeclampsia pathophysiology, and in addition to BMI, associated biomarkers with higher sensitivity and specificity, such as with adipokines from adipose tissue, are needed to enable clinical risk assessment. This study aimed to investigate obese pregnant women with and without PE by comparing clinical profiles and adipokine profiles specific to general adipose tissue (adiponectin and leptin). MATERIALS AND METHODS: This meta-analysis was conducted following the PRISMA and was registered in PROSPERO (CRD42023478706). We utilized Cochrane, Scopus, and PubMed/Medline databases. The Cochrane ROBINS-I instrument was employed to assess the quality of studies. Pooled standard mean difference (SMD) and p-value were analyzed using a random-effects model with the DerSimonian-Laird method, while subgroup analysis with the Chi-square test and the inconsistency index (I2) were used to assess potential sources of heterogeneity. RESULTS: Three observational studies included a total of 2,646 obese pregnant women and found that adiponectin was more likely to have a lower level in pregnant women with obesity [SMD=-0.32; 95% CI: -0.34-0.17, p=0.003] and leptin was more likely to be higher in obese pregnant women with PE rather than non-PE [SMD=0.53; 95% CI: -0.19-1.08, p<0.00001]. CONCLUSIONS: Adiponectin levels were more likely to be lower in pregnant women with obesity in the PE group than in the non-PE group, and leptin levels were more likely to be higher.

Diagnosis of preeclampsia using metabolomic biomarkers.

The diagnostic criteria for preeclampsia do not accurately reflect the pathophysiological characteristics of patients with preeclampsia. Conventional biomarkers and diagnostic approaches have proven insufficient to fully comprehend the intricacies of preeclampsia. This study aimed to screen differentially abundant metabolites as candidate biomarkers for preeclampsia. A propensity score matching method was used to perform a 1:1 match between preeclampsia patients (n = 70) and healthy control individuals (n = 70). Based on univariate and multivariate statistical analysis methods, the different characteristic metabolites were screened and identified. Least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently used to further screen for differentially abundant metabolites. A receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of the metabolites. A total of 1,630 metabolites were identified and quantified in maternal serum samples. Fifty-three metabolites were significantly increased, and two were significantly decreased in preeclampsia patients. The area under the curve (AUC) of the model composed of isobutyryl-L-carnitine and acetyl-leucine was 0.878, and the sensitivity and specificity in detecting preeclampsia were 81.4% and 87.1%, respectively. There are significant differences in metabolism between preeclampsia patients and healthy pregnant women, and a range of novel biomarkers have been identified. These findings lay the foundation for the use of metabolomic biomarkers for the diagnosis of preeclampsia.

Lipidomic signatures in patients with early-onset and late-onset Preeclampsia.

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.

Detection and assessment of immune and stromal related risk genes to predict preeclampsia: A bioinformatics analysis with dataset.

This study aimed to investigate immune score and stromal score-related signatures associated with preeclampsia (PE) and identify key genes for diagnosing PE using bioinformatics analysis. Four microarray datasets, GSE75010, GSE25906, GSE44711, and GSE10588 were obtained from the Gene Expression Omnibus database. GSE75010 was utilized for differential expressed gene (DEGs) analysis. Subsequently, bioinformatic tools such as gene ontology, Kyoto Encyclopedia of Genes and Genomes, weighted gene correlation network analysis, and gene set enrichment analysis were employed to functionally characterize candidate target genes involved in the pathogenesis of PE. The least absolute shrinkage and selection operator regression approach was employed to identify crucial genes and develop a predictive model. This method also facilitated the creation of receiver operating characteristic (ROC) curves, enabling the evaluation of the model's precision. Furthermore, the model underwent external validation through the other three datasets. A total of 3286 DEGs were identified between normal and PE tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed enrichments in functions related to cell chemotaxis, cytokine binding, and cytokine-cytokine receptor interaction. weighted gene correlation network analysis identified 2 color modules strongly correlated with immune and stromal scores. After intersecting DEGs with immune and stromal-related genes, 13 genes were selected and added to the least absolute shrinkage and selection operator regression. Ultimately, 7 genes were screened out to establish the risk model for discriminating preeclampsia from controls, with each gene having an area under the ROC curve >0.70. The constructed risk model demonstrated that the area under the ROC curves in internal and the other three external datasets were all greater than 0.80. A 7-gene risk signature was identified to build a potential diagnostic model and performed well in the external validation group for PE patients. These findings illustrated that immune and stromal cells played essential roles in PE during its progression.

Potential molecular mechanisms and clinical implications of piRNAs in preeclampsia: a review.

Preeclampsia is a multisystem progressive condition and is one of the most serious complications of pregnancy. Owing to its unclear pathogenesis, there are no precise and effective therapeutic targets for preeclampsia, and the only available treatment strategy is to terminate the pregnancy and eliminate the clinical symptoms. In recent years, non-coding RNAs have become a hotspot in preeclampsia research and have shown promise as effective biomarkers for the early diagnosis of preeclampsia over conventional biochemical markers. PIWI-interacting RNAs, novel small non-coding RNA that interact with PIWI proteins, are involved in the pathogenesis of various diseases at the transcriptional or post-transcriptional level. However, the mechanisms underlying the role of PIWI-interacting RNAs in the pathogenesis of preeclampsia remain unclear. In this review, we discuss the findings of existing studies on PIWI-interacting RNA biogenesis, functions, and their possible roles in preeclampsia, providing novel insights into the potential application of PIWI-interacting RNAs in the early diagnosis and clinical treatment of preeclampsia.

Role of hematological indices in predicting preeclampsia and its severity: retrospective case-control study.

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.

Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

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.

[Prevention of preeclampsia and its complications]. / Prévention de la prééclampsie et de ses complications.

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.

Inflammatory markers and their association with preeclampsia among pregnant women: A systematic review and meta-analysis.

The goal of this review was to investigate the levels of pro-inflammatory markers such as Tumour necrosis factor-α (TNF-α) Interlukin-6 (IL-6), C-reactive protein (CRP), Transforming growth factor-ß1 (TGF-ß1) and ferritin in pre-eclamptic and normotensive pregnant women. Using PubMed, ProQuest and Google Scholar databases, a literature search was carried out and case-control studies showing associations between inflammatory markers and preeclampsia in pregnancy published between 2010 and 2023 were included. The risk of bias was assessed by using the Newcastle Ottawa quality assessment scale. A random effect meta-analysis was performed and pooled difference in means with 95 % CI were reported. All statistical analyses were performed using R software. Out of 660 articles, 25 articles were included in the systematic review. The differences in means for TGF-ß1, CRP, ferritin and TNF-α levels between the preeclamptic women and normotensive women were 2.37 pg/mL [95 % CI: -1.66,6.39], 5.62 mg/L [95 % CI: -4.11,15.36], 32.93 ng/mL [95 % CI: -7.66,58.19] and 13.67 pg/mL [95 % CI: 4.20,23.14] respectively which showed moderate increase. The pooled differences in means for hs-CRP and IL-6 levels between the preeclamptic and normotensive women were 3.20 mg/L [95 % CI: 0.27,6.12] and 17.64 pg/mL [95 % CI: -8.36,43.64] respectively which showed significant increase. Sub-group analysis showed significant differences for CRP, ferritin and TNF-α levels across ethnicities. Meta-analysis demonstrates an increase in the maternal circulating levels of inflammatory markers such as hs-CRP, IL-6 and showed moderate increase in TGF-ß1, CRP, ferritin, TNF-α markers among women affected by preeclampsia compared to those with normotensive pregnancies.

Patterns of Gestational Hypertension or Preeclampsia Across 2 Pregnancies in Relationship to Chronic Hypertension Development: A Retrospective Cohort Study.

BACKGROUND: Gestational hypertension (GHTN) and preeclampsia are established risk indicators for chronic hypertension. While recurrence is associated with a greater risk, it is unclear whether there are differences in risk when these gestational complications occur for the first time in an earlier pregnancy versus first occurrence in a subsequent one. We hypothesized that the absence of recurrence reflects a transition toward a lower hypertension risk trajectory, whereas a new occurrence in a later pregnancy indicates a transition toward elevated risk. METHODS AND RESULTS: We analyzed linked data in Quebec, Canada, from public health care insurance administrative databases and birth, stillbirth, and death registries. Our retrospective cohort study included mothers with 2 singleton deliveries between April 1990 and December 2012. The primary exposure was patterns of GHTN or preeclampsia across 2 pregnancies (GHTN/preeclampsia in neither, first only, second only, or both). The outcome was incident chronic hypertension. We performed an adjusted multivariable Cox regression analysis. Among 431 980 women with 2 singleton pregnancies, 27 755 developed hypertension during the follow-up period. Compared with those without GHTN/preeclampsia, those with GHTN/preeclampsia only in the first pregnancy had a 2.7-fold increase in hazards (95% CI, 2.6-2.8), those with GHTN/preeclampsia only in the second had a 4.9-fold increase (95% CI, 4.6-5.1), and those with GHTN/preeclampsia in both pregnancies experienced a 7.3-fold increase (95% CI, 6.9-7.6). Patterns and estimates were similar when we considered GHTN and preeclampsia separately. CONCLUSIONS: The magnitude of hypertension risk is associated with the number and sequence of GHTN/preeclampsia-affected pregnancies. Considering both allows more personalized risk estimates.

A dynamic prediction model for preeclampsia using the sFlt-1/PLGF ratio combined with multiple factors.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-related multi-organ disease and a significant cause of incidence rate and mortality of pregnant women and newborns worldwide. Delivery remains the only available treatment for PE. This study aims to establish a dynamic prediction model for PE. METHODS: A total of 737 patients who visited our hospital from January 2021 to June 2022 were identified according to the inclusion and exclusion criteria, forming the primary dataset. Additionally, 176 singleton pregnant women who visited our hospital from July 2022 to November 2022 comprised the verification set. We investigated different gestational weeks of sFlt-1/PLGF (soluble FMS-like tyrosine kinase-1, placental growth factor) ratio combined with maternal characteristics and routine prenatal laboratory results in order to predict PE in each trimester. Multivariate logistic regression was used to establish the prediction model for PE at different gestational weeks. The discrimination, calibration, and clinical validity were utilized to evaluate predictive models as well as models in external validation queues. RESULTS: At 20-24 weeks, the obtained prediction model for PE yielded an area under the curve of 0.568 (95% confidence interval, 0.479-0.657). At 25-29 weeks, the obtained prediction model for PE yielded an area under the curve of 0.773 (95% confidence interval, 0.703-0.842)and 0.731 (95% confidence interval, 0.653-0.809) at 30-34 weeks. After adding maternal factors, uterine artery pulsation index(Ut-IP), and other laboratory indicators to the sFlt-1/PLGF ratio, the predicted performance of PE improved. It found that the AUC improved to 0.826(95% confidence interval, 0.748 ∼ 0.904) at 20-24 weeks, 0.879 (95% confidence interval, 0.823 ∼ 0.935) at 25-29 weeks, and 0.862(95% confidence interval, 0.799 ∼ 0.925) at 30-34 weeks.The calibration plot of the prediction model indicates good predictive accuracy between the predicted probability of PE and the observed probability. Furthermore, decision-curve analysis showed an excellent clinical application value of the models. CONCLUSION: Using the sFlt-1/PLGF ratio combined with multiple factors at 25-29 weeks can effectively predict PE, but the significance of re-examination in late pregnancy is not significant.

The Relationship between the Level of Coagulative Function Hypertensive Disorder Complicating Pregnancy.

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.