Diagnosis Of Preeclampsia Research Articles

Real-World Evidence for Utility of Serum sFlt-1/PlGF Test for Routine Clinical Evaluation of Hospitalized Women with Hypertensive Disorders of Pregnancy

An imbalance of the anti-angiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1), and pro-angiogenic factor, placental growth factor (PlGF) in the circulation is a reliable predictor for development of preeclampsia with severe features and related adverse outcomes. In 2023, the United States (US) Food and Drug Administration approved a serum sFlt-1/PlGF test at a cut-off of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy (HDP) for the progression to preeclampsia with severe features between 23 and 35 weeks. The purpose of this study was to generate real-world evidence for clinical utility for serum sFlt-1/PlGF test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within two weeks of testing among hospitalized patients with HDP. Hospitalized patients with HDP between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to Jan 2024 following implementation of serum sFlt-1/PlGF testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (PlGF and sFlt-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines based on biomarkers but made pragmatic management decisions independently. Results of sFlt-1/PlGF tests were available to clinicians within 24 hours of venipuncture. The association between sFlt-1/PlGF ≥ 40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed. Of the 65 patient encounters, 36 had a sFlt-1/PlGF < 40 (55.4%). The rate of delivery for indications related to HDP within two weeks was significantly lower among encounters with a low ratio versus high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted HR 7.52, 95% CI: 3.05, 18.54; p < 0.001). A diagnosis of preeclampsia with severe features within two weeks of testing was also less likely among the encounters with sFlt-1/PlGF ratio < 40 when compared to sFlt-1/PlGF ratio ≥ 40 (2/36 [5.6%] versus 23/29 [79.3%], p<0.001; PPV 79% [95% CI: 0.65, 0.94] and NPV 0.94 [95% CI: 0.87, 1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within two weeks of testing were 6.13 and 0.09 respectively. Encounters with an sFlt-1/PlGF ratio <40 were less likely to experience a maternal or fetal adverse event as compared to encounters with sFlt-1/PlGF ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], p=0.01). Among 36 encounters involving low sFlt-1/PlGF values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed based on biomarkers and none developed preeclampsia with severe features or adverse outcomes at two weeks. The median latency defined as days between biomarker measurement and delivery in patients with low biomarker ratio was 33 (IQR 23, 47) versus 7 (IQR 4, 14) days among patients with a high ratio (p<0.001). Corticosteroid use within two weeks was also significantly reduced in the low biomarker group when compared to high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], p<0.001). In this study, incorporation of sFlt-1/PlGF ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with HDP in the US. Among patients with a low ratio, pregnancy may be prolonged which resulted in better neonatal outcomes without harm to the mother.

Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants

Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Maternal preeclampsia and FGR in very preterm infants. The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Postpartum Bilateral Nerve Palsy: A Harbinger for Preeclampsia?

Objective: To report a case of postpartum bilateral facial weakness that preceded the diagnosis of preeclampsia. Introduction: Bell’s palsy is a neuromuscular disorder that can cause paralysis or weakness of the face. It is the most common cause of unilateral facial weakness; however, bilateral weakness is rare. Bell’s palsy is one of the most common neuromuscular disorders observed in pregnancy, though the link between the two is not entirely clear. Proposed etiologies include reactivation of human herpes viruses, immune mediated inflammatory demyelination of the facial nerve, and microangiopathy as a result of systemic hypertension. There have been several case reports and studies suggesting a correlation between preeclampsia and Bell’s palsy. We present a rare case of postpartum bilateral Bell’s palsy in the setting of preeclampsia. Design: Case report. Results: Our patient is a 24 year-old G6P4116 Caucasian woman with no significant past medical history who presented with bilateral facial weakness and headache. She was postpartum day four from a spontaneous vaginal delivery of dichorionic diamniotic twins at 35 weeks at an outside hospital. She denied any elevated blood pressures during her pregnancy. Initially, on postpartum day two she had reported a severe headache that initially affected her occipital region bilaterally before migrating to her ears and forehead. At this time the patient was normotensive and was discharged home on analgesics. On postpartum day three, she returned to another emergency department with a worsening, severe headache. She was sent home with a diagnosis of anxiety. On postpartum day four, her symptoms persisted and she came to the emergency department at our facility. During our initial evaluation, her blood pressure was 170/98. She was admitted for severe preeclampsia and given IV magnesium and nifedipine. However, her headache persisted and she developed bilateral facial weakness, neck pain, and swelling. She reported that she was unable to move her face and had difficulty smiling. Her face was expressionless. She denied nausea, vomiting, dysphagia, double vision, gait disturbances, hearing loss, fever, shortness of breath, numbness, or tingling. She denied recent travel, sick contacts, or animal or tick bites. She was evaluated by neurology and her initial physical exam revealed intact cranial nerves, though the patient appeared to have difficulty squeezing her eyes shut and smiling. Periorbital edema was noted. Facial symmetry and sensation were intact bilaterally. She had difficulty saying the letter “P.” Her MRIs of both brain and cervical spine, chest x-ray, and lumbar puncture were all normal. Our working diagnoses included bilateral Bell’s palsy, Guillain-Barré and Miller-Fischer syndromes. The antibody panel drawn for Miller-Fischer syndrome subsequently resulted as negative. Our patient received three days of IVIG and was discharged on a week supply of prednisone 60mg with a taper thereafter. At discharge, she had severe bilateral facial droop. She was unable to puff out her cheeks or raise her eyebrows. Neurology recommended outpatient follow up. One month after discharge she had residual right sided facial droop, but the deficits of the left side of her face had mostly resolved. Discussion: Current literature suggests a correlation between preeclampsia and Bell’s palsy. There is some thought that elevated blood pressure leads to facial nerve compression secondary to edema or microemboli. One report suggested that the onset of Bell’s palsy antepartum or postpartum may be a predictor of preeclampsia. An English language PUBMED search revealed six case reports on bilateral Bell’s palsy in either the pregnant or postpartum state. Cases reported occurred in either the third trimester or within the first week postpartum. This was consistent with the onset of our patient’s symptoms during her first week postpartum. In one case, neurological symptoms preceded preeclampsia. Our patient complained of headaches and neck pain prior to having elevated blood pressures. Three of these cases included twin gestations, as did our case. Outcomes varied, with some patients seeing complete resolution of symptoms within weeks to others having recurring symptoms over a year. Providers should consider the relationship between preeclampsia and Bell’s palsy when treating pregnant or postpartum patients with new onset neurological symptoms. Pregnant and postpartum patients are at greater than three times increased risk for Bell’s palsy and have more severe symptoms and longer recovery times compared to the average population. It is important that obstetricians and gynecologists assess for signs of preeclampsia in pregnant or postpartum patients with concerns for Bell’s palsy, as well as refer patients for a complete neurological workup. Ultimately, more research is needed to further understand the relationship between preeclampsia and Bell’s palsy.

Postpartum Bilateral Nerve Palsy: A Harbinger for Preeclampsia?

Objective: To report a case of postpartum bilateral facial weakness that preceded the diagnosis of preeclampsia. Introduction: Bell’s palsy is a neuromuscular disorder that can cause paralysis or weakness of the face. It is the most common cause of unilateral facial weakness; however, bilateral weakness is rare. Bell’s palsy is one of the most common neuromuscular disorders observed in pregnancy, though the link between the two is not entirely clear. Proposed etiologies include reactivation of human herpes viruses, immune mediated inflammatory demyelination of the facial nerve, and microangiopathy as a result of systemic hypertension. There have been several case reports and studies suggesting a correlation between preeclampsia and Bell’s palsy. We present a rare case of postpartum bilateral Bell’s palsy in the setting of preeclampsia. Design: Case report. Results: Our patient is a 24 year-old G6P4116 Caucasian woman with no significant past medical history who presented with bilateral facial weakness and headache. She was postpartum day four from a spontaneous vaginal delivery of dichorionic diamniotic twins at 35 weeks at an outside hospital. She denied any elevated blood pressures during her pregnancy. Initially, on postpartum day two she had reported a severe headache that initially affected her occipital region bilaterally before migrating to her ears and forehead. At this time the patient was normotensive and was discharged home on analgesics. On postpartum day three, she returned to another emergency department with a worsening, severe headache. She was sent home with a diagnosis of anxiety. On postpartum day four, her symptoms persisted and she came to the emergency department at our facility. During our initial evaluation, her blood pressure was 170/98. She was admitted for severe preeclampsia and given IV magnesium and nifedipine. However, her headache persisted and she developed bilateral facial weakness, neck pain, and swelling. She reported that she was unable to move her face and had difficulty smiling. Her face was expressionless. She denied nausea, vomiting, dysphagia, double vision, gait disturbances, hearing loss, fever, shortness of breath, numbness, or tingling. She denied recent travel, sick contacts, or animal or tick bites. She was evaluated by neurology and her initial physical exam revealed intact cranial nerves, though the patient appeared to have difficulty squeezing her eyes shut and smiling. Periorbital edema was noted. Facial symmetry and sensation were intact bilaterally. She had difficulty saying the letter “P.” Her MRIs of both brain and cervical spine, chest x-ray, and lumbar puncture were all normal. Our working diagnoses included bilateral Bell’s palsy, Guillain-Barré and Miller-Fischer syndromes. The antibody panel drawn for Miller-Fischer syndrome subsequently resulted as negative. Our patient received three days of IVIG and was discharged on a week supply of prednisone 60mg with a taper thereafter. At discharge, she had severe bilateral facial droop. She was unable to puff out her cheeks or raise her eyebrows. Neurology recommended outpatient follow up. One month after discharge she had residual right sided facial droop, but the deficits of the left side of her face had mostly resolved. Discussion: Current literature suggests a correlation between preeclampsia and Bell’s palsy. There is some thought that elevated blood pressure leads to facial nerve compression secondary to edema or microemboli. One report suggested that the onset of Bell’s palsy antepartum or postpartum may be a predictor of preeclampsia. An English language PUBMED search revealed six case reports on bilateral Bell’s palsy in either the pregnant or postpartum state. Cases reported occurred in either the third trimester or within the first week postpartum. This was consistent with the onset of our patient’s symptoms during her first week postpartum. In one case, neurological symptoms preceded preeclampsia. Our patient complained of headaches and neck pain prior to having elevated blood pressures. Three of these cases included twin gestations, as did our case. Outcomes varied, with some patients seeing complete resolution of symptoms within weeks to others having recurring symptoms over a year. Providers should consider the relationship between preeclampsia and Bell’s palsy when treating pregnant or postpartum patients with new onset neurological symptoms. Pregnant and postpartum patients are at greater than three times increased risk for Bell’s palsy and have more severe symptoms and longer recovery times compared to the average population. It is important that obstetricians and gynecologists assess for signs of preeclampsia in pregnant or postpartum patients with concerns for Bell’s palsy, as well as refer patients for a complete neurological workup. Ultimately, more research is needed to further understand the relationship between preeclampsia and Bell’s palsy.

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction

BackgroundHypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies. MethodsPreeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. ResultsRecruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e’ (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e’ (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001). ConclusionsPostpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study

A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25–30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control’s DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.

Construction of a pathway-level model for preeclampsia based on gene expression data.

Preeclampsia (PE) is a heterogeneous disease that seriously affects the health of mothers and fetuses. Lack of detection assays, its diagnosis and intervention are often delayed when the clinical symptoms are atypical. Using personalized pathway-based analysis and machine learning algorithms, we built a PE diagnosis model consisting of nine core pathways using multiple cohorts from the Gene Expression Omnibus database. The model showed an area under the receiver operating characteristic (AUROC) curve of 0.959 with the data from the placental tissue samples in the development cohort. In the two validation cohorts, the AUROCs were 0.898 and 0.876, respectively. The model also performed well with the maternal plasma data in another validation cohort (AUROC: 0.815). Moreover, we identified tyrosine-protein kinase Lck (LCK) as the hub gene in this model and found that LCK and pLCK proteins were downregulated in placentas from PE patients. The pathway-level model for PE can provide a novel direction to develop molecular diagnostic assay and investigate potential mechanisms of PE in future studies.

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

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). 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. 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.). 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.

Factors Associated with Refractory Severe Hypertension in Patients with Preeclampsia.

This study aimed to identify factors associated with refractory severe hypertension that does not resolve after an initial dose of antihypertensive medication in patients with preeclampsia. This was a retrospective study of all pregnant and postpartum individuals with a diagnosis of preeclampsia, superimposed preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, or eclampsia who delivered at 22 weeks or greater at a single academic institution from 2010 to 2020. Inclusion criteria were patients with preeclampsia who developed severe hypertension (systolic pressure ≥160 mm Hg or diastolic pressure ≥110 mm Hg) and received antihypertensive medications for acute severe hypertension. We defined refractory severe hypertension as a systolic blood pressure of ≥160 mm Hg or a diastolic blood pressure of ≥110 mm Hg that did not improve after receiving the initial treatment. To evaluate for factors associated with refractory severe hypertension, we developed multivariable modified Poisson regression using all variables with p-value <0.1 on bivariable analysis and calculated adjusted relative risks (aRRs) with 95% confidence intervals (95% CIs). Of 850, 386 (45.4%) had refractory severe hypertension and 464 (54.6%) responded to the initial antihypertensive medications. Factors associated with refractory severe hypertension included higher body mass index (BMI), chronic hypertension, and higher systolic pressure. Every 5 kg/m2 increase in BMI was associated with a 7% increased risk of refractory severe hypertension (aRR = 1.07; 95% CI: 1.02-1.12). Every 10 mm Hg increase in systolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.04-1.17). Chronic hypertension was associated with a 25% increased risk of refractory severe hypertension (aRR = 1.25; 95% CI: 1.01-1.56) in the diastolic pressure model. Refractory severe hypertension was associated with elevated BMI, chronic hypertension, and higher systolic blood pressure. · Risk factors for refractory severe hypertension are not well-known.. · Almost half of the patients had refractory severe hypertension.. · Higher BMI, chronic hypertension, and higher systolic pressure were the risk factors.. · These patients would require closer follow-up and prompt response to vital signs..

Perinatal Outcomes of Immigrant Mothers and Their Infants Born Very Preterm across Germany.

In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed. We tested whether mothers' immigrant status and language barriers are associated with perinatal health and short-term neonatal outcomes. The data are from the national multi-centre German Neonatal Network (GNN) cohort, including VP births from 2009 onwards. In total, 3606 (n = 1738 female) children were assessed, and 919 (n = 449 female) of these children had immigrant backgrounds. Immigrant status was operationalised as a binary variable based on the children's mothers' countries of birth (born in Germany vs. foreign-born). Self-reported home language (L1) was used to calculate the average linguistic distance to German as one continuous variable. Mixed-effects models showed that two out of fourteen effects of interest survived the adjustment for known confounders and accounting for the nestedness of data within birth hospitals. Linguistic distance from mothers' L1s to German was independently associated with diagnoses of preeclampsia (OR = 1.01, 95% CI = [1.00, 1.01]). Infants of foreign-born mothers had higher odds for amniotic infection syndrome (AIS; OR = 1.45 [1.13, 1.86]) than infants of German mothers. Our findings from this large multi-centre longitudinal cohort of VP-born children indicate that maternal immigrant status and language barriers have limited impact on perinatal health and severe neonatal outcomes. This suggests that, regardless of background or language skills, there may be few inequalities in the perinatal health of pregnant women and their newborn preterm infants.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks’ Gestational Age

To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging (MRI) at term-equivalent age. In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T MRI scan between 39 through 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, preeclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5-53%) higher brain abnormality scores than those without HDP exposure (p=0.02), primarily driven by increased white matter injury/abnormality scores (p=0.01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (p=0.02) contributed to brain abnormality scores (22% of the total effect). Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Bioinformatics identification and validation of maternal blood biomarkers and immune cell infiltration in preeclampsia: An observational study.

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.

Review of Laboratory Testing and Biomarker Screening for Preeclampsia

The purpose of this review is to elucidate the different laboratory and biomarker testing methods available for screening and diagnosis of preeclampsia. These include routine testing, such as blood pressure readings, qualitative and quantitative urine testing, complete blood count with platelets, serum creatinine levels, liver chemistries, and serum bilirubin levels. This review also details the use of non-routine testing, such as screening for angiogenic and anti-angiogenic markers, such as placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Blood pressure measurements and proteinuria are the most routinely used screening tools used for preeclampsia and there are limited data on the utility of other screening techniques because of a greater focus on the etiology and treatment of preeclampsia. Similarly, serum angiogenic biomarkers are not routinely collected, so there is limited evidence regarding using them as screening tools for preeclampsia and more data are needed to determine their significance in the screening and diagnosis of preeclampsia.

PPP2R2A inhibition contributes to preeclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells

BackgroundThe precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE.MethodsReverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay.ResultsPPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment.ConclusionPPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment.

Unveiling an oxidative stress-linked diagnostic signature and molecular subtypes in preeclampsia: novel insights into pathogenesis

Preeclampsia (PE) is a complex pregnancy disorder characterized by hypertension and organ dysfunction, affecting both maternal and fetal health. Oxidative stress has been implicated in the pathogenesis of PE, but the underlying molecular mechanisms remain poorly understood. In this study, we aimed to identify a diagnostic signature and molecular subtypes associated with oxidative stress in PE to gain novel insights into its pathogenesis. The ssGSEA algorithm evaluated oxidative stress-related pathway scores using transcriptional data from the GSE75010 dataset. Oxidative stress-related genes (ORGs) were co lected from these pathways, and hub ORGs associated with PE were identified using the LASSO and logistic regression models. A nomogram prediction model was constructed using the identified ORGs. Consensus clustering identified two molecular subgroups related to oxidative stress, labeled as C1 and C2, with unique immune characteristics and inflammatory pathway profiles. Seventy ORGs associated with oxidative stress, ce l death, and inflammation-related pathways were identified in PE. EGFR, RIPK3, and ALAD were confirmed as core ORGs for PE biomarkers. The C1 and C2 subgroups exhibited distinct immune characteristics and inflammatory pathway profiles. This study provides novel insights into the role of oxidative stress in PE pathogenesis. A diagnostic signature and molecular subtypes associated with oxidative stress were identified, which may improve understanding, diagnosis, and management of PE.

Emergency cesarean section of a patient with refractory status epilepticus: A case report of challenges during anesthesia.

Maternal epilepsy is a critical condition that can significantly affect mothers and fetuses. Notably, the admission of a laboring mother with uncontrolled refractory status epilepticus (RSE) to the operating room presents a challenging scenario for anesthesiologists. A 30-year-old primigravida was transferred to the operating room for an emergency cesarean section. Cesarean section was performed after a provisional diagnosis of preeclampsia was made. Cesarean section was performed under general anesthesia. During the postoperative period, the patient exhibited no seizure activity in the brain; however, she experienced mild cognitive dysfunction for up to 6 months postdelivery. The neonate were discharged without any complications. Inducing anesthesia in pregnant women with ongoing seizure activity are challenging; however, anesthesiologists provide judgment based on the balance between the safety of the mother and fetus and the balance between patient monitoring and the progression of anesthesia. This challenge can be addressed through multidisciplinary collaboration.

Raised levels of chemerin in women with preeclampsia: A meta-analysis.

Chemerin is a multifunctional adipokine associated with systemic inflammation, angiogenesis, and oxidative stress. Emerging evidence suggests a potential link between chemerin and the pathogenesis of preeclampsia (PE). In this systematic review and meta-analysis, we aimed to evaluate the serum chemerin levels in women with PE. A systematic search was conducted across Medline, Web of Science, and Embase databases from inception until April 15, 2023, to identify studies comparing serum chemerin levels in pregnant women with and without PE. A random-effects model was employed to pool the results, accounting for heterogeneity. Thirteen datasets from 10 observational studies, encompassing 832 women with PE and 1298 healthy pregnant women, were analyzed. The pooled findings indicated a statistically significant elevation in serum chemerin levels in women with PE compared to controls (mean difference [MD] = 89.56 ng/mL, 95% confidence interval [CI] 62.14 - 116.98; P < 0.001; I2 = 87%). The subgroup analysis revealed consistent findings across studies that measured chemerin levels before or after the diagnosis of PE, studies that did or did not match the body mass index (BMI), and studies with varying quality scores (P values for subgroup differences were all > 0.05). Compared to controls, women with severe PE exhibited a significantly greater increase in serum chemerin levels than those with mild PE (P value for subgroup difference = 0.007). Additionally, meta-regression analysis results suggested that the mean BMI of the included pregnant women might positively modify the difference in circulating chemerin levels between women with and without PE (coefficient = 8.92; P = 0.045). In conclusion, this meta-analysis suggests a positive correlation between elevated serum chemerin levels and PE diagnosis in comparison to pregnant women without the condition.

Effect of Hyponatremia in Preeclamptic Patients With Severe Features [ID 2683491

INTRODUCTION: Hyponatremia, although common in expectant women with preeclampsia, has not been well studied in a multicenter fashion, and it is unknown whether it is associated with adverse events related to severe preeclampsia. Our primary objectives are to assess the clinical characteristics and emergency therapy applied to participants diagnosed with preeclampsia. We hypothesize that hyponatremia present in preeclamptic patients with severe features is associated with greater use of emergency hypertensives, antenatal steroids, and cesarean delivery. METHODS: This is a retrospective cohort study utilizing a multicenter electronic health record database (TriNetX). We collected and evaluated the following data of participants aged 15–54 years with a diagnosis of preeclampsia with severe features: demographics, diagnostic codes, medication codes, procedure codes, deaths, and laboratory results. RESULTS: A total of 2,901 participants (215 [7.4%] with a sodium level below 134 mEq/L and 2,686 [92.6%] with a sodium level above 135 mEq/L) were included. A higher proportion of participants in the below 134 sodium group received emergency antihypertensives (165 [76.7%] versus 1,811 [67.4%]; P=.01), antenatal steroids (103 [47.9%] versus 953 [35.5%]; P=.001), and cesarean section (27 [12.6%] versus 97 [3.6%]; P&lt;.001). CONCLUSION: We found that hyponatremia may be associated with emergency antihypertensive use, antenatal steroid use, and cesarean section in patients with preeclampsia with severe features. Future research is needed to determine whether routine sodium levels assessed in preeclamptic subjects with severe features identify subjects at risk of receiving these treatments.

Questioning the Value of Urine Protein for the Diagnosis of Hypertensive Disorders of Pregnancy [ID 2683605

INTRODUCTION: Preeclampsia with severe features (PreE w/SF) is often preceded with a diagnosis of gestational hypertension (gHTN) or preeclampsia without severe features (PreE w/o SF). These diagnoses remain differentiated via a 24-hour urine protein (24 UP) or a urine–protein creatinine ratio (PCR). We examine the utility of the 24 UP/PCR in differentiating the progression of gHTN or PreE w/o SF to PreE w/SF. METHODS: We created a retrospective cohort study of 1,687 patients who delivered a live-born neonate at our urban, academic hospital between September 2011 and September 2021. All patients had an initial diagnosis of either gHTN or PreE w/o SF. Patients with chronic hypertension or an initial diagnosis of PreE w/SF were excluded. We performed descriptive and inferential statistics including chi-square. RESULTS: We identified 910 (54%) patients initially diagnosed with gHTN and 777 (46%) PreE w/o SF. A total of 972 (57.7%) reported to be Black and 518 (30.1%) Hispanic. The rate of progression to PreE w/SF did not differ across those with an initial diagnosis of gHTN (n=147 [16%]) or PreE w/o SF (n=153 [19%]; X2 (1)=3.55, P&gt;.05). Timing of initial diagnosis being antenatal or postnatal was not predictive of disease progression. CONCLUSION: We found no clinical significance of a 24 UP/PCR in predicting progression to PreE w/SF from gHTN or PreE w/o SF. Performing a 24 UP or PCR takes health care dollars and patients' time, which has economic and social effects. Although further investigation is needed, our findings support eliminating 24 UP/PCR as a diagnostic criterion.

Prognostic value of angiogenic markers in pregnancy with fetal growth restriction.

Pregnancies with fetal growth restriction (FGR) are at increased risk for pre-eclampsia. Angiogenic markers including soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by FGR, but their utility for predicting pre-eclampsia in growth-restricted pregnancies is uncertain. This study aimed to evaluate the prognostic value of angiogenic markers for predicting the development of pre-eclampsia in pregnancies with FGR and suspected pre-eclampsia. This was a retrospective study of singleton pregnancies with FGR, defined according to Delphi consensus criteria, which underwent sampling of sFlt-1 and PlGF for suspicion of pre-eclampsia at the Medical University of Vienna, Vienna, Austria, between 2013 and 2020. Women with an established diagnosis of pre-eclampsia at sampling were excluded. Cox regression analysis and logistic regression analysis were performed to evaluate the association of angiogenic markers with the development of pre-eclampsia at various timepoints. In this cohort of 93 women, pre-eclampsia was diagnosed in 14 (15.1%) women within 1 week after sampling, 21 (22.6%) within 2 weeks after sampling and 38 (40.9%) at any time after assessment. The sFlt-1/PlGF ratio consistently showed a stronger association with the development of pre-eclampsia compared to sFlt-1 or PlGF alone (pre-eclampsia within 1 week: area under the receiver-operating-characteristics curve, 0.87 vs 0.82 vs 0.72). Models including the sFlt-1/PlGF ratio were associated more strongly with pre-eclampsia hazard compared to models including sFlt-1 or PlGF alone (concordance index, 0.790 vs 0.759 vs 0.755). The risk classification capability of the sFlt-1/PlGF ratio decreased after the 2-week timepoint. The established cut-off value for the sFlt-1/PlGF ratio of < 38 was effective for ruling out pre-eclampsia within 2 weeks, with a negative predictive value of 0.933 and sensitivity of 0.952. Use of the sFlt-1/PlGF ratio is preferrable to the use of PlGF alone for the prediction of pre-eclampsia in pregnancies with FGR. Established cut-offs for ruling out the development of pre-eclampsia in the short term seem to be effective in these patients. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.