Serum macrophage stimulating protein α-chain and uterine artery Doppler ultrasound in the first trimester for the prediction of preeclampsia.

To assess how effective macrophage stimulating protein α-chain (MSP-α) combined with uterine artery Doppler is in predicting preeclampsia in singleton pregnancies during 11-13+6 weeks of gestation. This prospective observational study included singleton pregnant women who attended antenatal care at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University between December 2021 and April 2023, during 11-13+6 weeks of gestation. Serum MSP-α levels were collected and uterine artery Doppler ultrasound was performed. Pregnancy outcomes were recorded, and the predictive values of these tests were determined to predict preeclampsia. A total of 365 patients, with 21 cases of preeclampsia (5.8%), were analyzed. Serum MSP-α levels were higher in pregnant women who developed preeclampsia than those who did not (899.7 ± 550.1 ng/ml vs 642.5 ± 466.1 ng/ml, p = 0.016). The mean pulsatility index of the uterine artery and the presence of diastolic notching were not significantly different between the groups. As a cut-off value for predicting preeclampsia, using serum MSP-α levels higher than 1.0 multiple of median for gestational age, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.4%, 50.3%, 8.1%, and 96.7%, respectively. Additionally, when abnormal serum MSP-α levels were combined with a uterine artery Doppler pulsatility index above the 95th percentile and bilateral notching as predictive values for preeclampsia, the sensitivity was 85.7%, specificity was 18.3%, PPV was 6.0%, and NPV was 95.5%. Serum MSP-α alone at 11-13+6 weeks of gestation was effective in predicting preeclampsia. However, the use of serum MSP-α in combination with uterine artery Doppler increased sensitivity but reduced specificity for the prediction of preeclampsia.

SARS-CoV-2 seroprevalence and preeclampsia markers in Mozambican pregnant women with perinatal loss.

BACKGROUND: SARS-CoV-2 infection during pregnancy is known to be associated with poor pregnancy outcomes, including pre-eclampsia (PE), prematurity, perinatal and maternal mortality. Data on the burden of SARS-CoV-2 infection among pregnant women and their offspring in Sub-Saharan Africa is limited. We aimed to estimate SARS-CoV-2 seroprevalence and determine PE biomarkers in Mozambican pregnant women with perinatal loss. METHODS: A cross-sectional study was conducted among women who had a fetal or an early neonatal death at the Maputo Central Hospital (MCH), Mozambique. Anti-SARS-CoV-2 IgG/IgM were determined in maternal and umbilical cord blood and PE biomarkers (sFlt-1 and PIGF) in maternal blood. SARS-CoV-2 RT-PCR was performed in placenta and fetal lung biopsies from participants found to be SARS-CoV-2 seropositive. RESULTS: A total of 100 COVID-19 unvaccinated women were included in the study from March 2021 to April 2022. Total SARS-CoV-2 antibodies were detected in 68 [68%; 95CI (58 - 76)] maternal and 55 [55%; 95CI (54 - 74)] cord blood samples. SARS-CoV-2 IgM was detected in 18 cord blood samples and a positive placental RT-PCR in three of these participants. The proportion of women with moderate to high sFlt-1/PIGF ratio was higher in SARS-CoV-2 seropositive women than in those seronegative (71.2% vs 28.8%, p = 0.339), although the difference was not statistically significant. CONCLUSIONS: SARS-CoV-2 seroprevalence among Mozambican women with perinatal loss was high during the second pandemic year, and there was evidence of vertical transmission in stillbirths. Findings also suggest that maternal SARS-CoV-2 infection may increase the risk of developing PE.

Can Blood Inflammatory Markers Identify Pregnant Women with Preeclampsia? Still a Controversial Issue.

BACKGROUND: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus. OBJECTIVES: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies. METHODS: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis. RESULTS: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups. CONCLUSIONS: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

Targeted metabolomic analysis of early-trimester serum identifies potential mechanisms for late-onset preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder. Late-onset (Lo)-PE can cause serious complications in both the mother and child. This study aimed to explore biomarkers for elucidating the mechanisms underlying Lo-PE, via a metabolomic analysis of first-trimester maternal serum. METHODS: This study was conducted at Fukushima Regional Center as an adjunct to Japan Environment and Children Study and included 12 patients with Lo-PE matched to 12 women with healthy pregnancies. Capillary electrophoresis-mass spectrometry-based quantitative analyses of charged metabolites were performed on first-trimester maternal serum samples. RESULTS: Overall, 183 charged metabolites were identified. The peak area of glucosamine was significantly higher for the first-trimester sera of patients with Lo-PE than that for controls. Conversely, the peak area of serotonin was significantly decreased in the sera of patients with Lo-PE. CONCLUSIONS: During early pregnancy, glucosamine and serotonin levels in maternal serum may serve as early biomarkers for Lo-PE. As part of preconception care, pre-pregnancy dietary habits and mental health could potentially prevent Lo-PE onset.

Causal association of sex hormone-binding globulin on gestational hypertension and pre-eclampsia: a two-sample Mendelian randomization study.

OBJECTIVES: Pre-eclampsia (PE) and gestational hypertension (GH) are two different categories of hypertensive disorders of pregnancy. Given earlier observational research, the relationship between sex hormone-binding globulin (SHBG) and a higher risk of GH/PE is still up for dispute. Hence, the present investigation aimed to examine the possible link between SHBG and the likelihood of GH/PE. METHODS: As a first stage, single nucleotide polymorphisms from summary-level genome-wide association studies were tightly screened using quality-control techniques. Afterward, we utilized a two-sample Mendelian randomization (MR) study to examine the causal impact of SHBG on the likelihood of GH/PE. There was no indication of a relationship between blood SHBG level (n = 214,989) and GH/PE (1864 cases and 461,069 controls) in the initial study. Consensus results were obtained from the replicated analysis, which utilized MR estimates based on serum SHBG level(n = 214,989) for GH (4255 cases and 114,735 controls). RESULTS: The findings did not indicate any proof of a cause-and-effect connection between SHBG and the likelihood of GH/PE (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.999 - 1.00, p = .34). Replicate analysis also revealed similar patterns (OR = 0.92, 95%CI = 0.82-1.05, p = .21). The above findings were demonstrated to have a strong level of robustness. CONCLUSIONS: The findings of this research did not offer definitive proof to endorse the idea that SHBG has a direct causal impact on the likelihood of GH/PE, which goes against numerous widely accepted observational studies. To ascertain the potential processes behind the relationships seen in observational studies, more investigation is needed.

Predictive biomarkers of preeclampsia severity in a low resource setting: Role of red blood cell indices, NLR, and albumin-to-creatinine ratio.

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p<0.001), NLR (5.66% vs 4.1%; p<0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p<0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/µL vs 27.0 × 106/µL; p=0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting.

Fetoplacental unit involvement in uric acid production in women with severe preeclampsia: a prospective case control pilot study.

PURPOSE: Preeclampsia (PE) is a common complication of pregnancy that carries significant risks for both the mother and the fetus, and is frequently accompanied by hyperuricemia, yet the exact source of elevated uric acid (UA) levels remains partially elucidated. Several potential origins for increased UA levels include abnormal renal function, increased tissue breakdown, and increased activity of the enzyme Xanthine Oxidase (XO). The aim of the study was to determine serum levels of UA and XO not only in maternal serum, but also in umbilical vein (UV) and umbilical artery (UA) and explore their possible role in PE development. METHODS: A prospective case-control pilot study was conducted in women who were found positive for PE with severe features, and had elevated UA levels above 6 mg/dL, with normotensive pregnant women serving as controls. Renal function, UA and XO levels were measured in maternal, UV and UA serums immediately after delivery. They were then compared between PE (n = 21) and control (n = 18) groups, as well as across all mediums (maternal, UV and UA) among the total study sample (N = 39). Diastolic blood pressure (DBP) was also measured immediately following delivery. RESULTS: The mean serum maternal creatinine levels did not differ significantly between groups (0.65 ± 0.03 vs 0.6 ± 0.07, p = 0.13). Both mean maternal serum UA and XO concentrations were higher in PE group than in control (7.3 ± 1.2 vs 4.2 ± 0.9, p < 0.01 and 3.6 ± 3.5 Vs 1.7 ± 0.8, p < 0.01, respectively). The mean UV and UA serum XO concentrations were significantly higher in PE group compared to control (4.2 ± 3.6 vs 2.2 ± 1.4, p < 0.01 and 4.2 ± 3.6 vs 2.1 ± 1.5, p < 0.01, respectively). Polynomial fit correlation test demonstrated a significant association between maternal DBP and UV XO concentration for all the total study participants (p = 0.03). CONCLUSION: Despite preserved renal functions, UA and XO levels were elevated in women with PE. Importantly, this pattern was found to be applied to the feto-placental unit as well, which may indicate an active involvement of the fetus in the hypoxic process. Further study is needed to clarify the possible role of the feto-placental unit in pregnancies complicated by PE.

Interleukin-6 (-174G/C), Interleukin-1ß (-511 C/T), and Apolipoprotein B-100 (2488 C/T) Gene Polymorphism in Pre-Eclampsia.

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1ß, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1ß, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy-Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1ß-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy-Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1ß, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy-Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied.

Immunological Profiling of CD8+ and CD8- NK Cell Subpopulations and Immune Checkpoint Alterations in Early-Onset Preeclampsia and Healthy Pregnancy.

Despite the numerous studies on the clinical aspects of early-onset preeclampsia, our understanding of the immunological consequences of inadequate placenta development remains incomplete. The Th1-predominance characteristic of early-onset preeclampsia significantly impacts maternal immunotolerance, and the role of immune checkpoint molecules in these mechanisms is yet to be fully elucidated. Our study aims to fill these crucial knowledge gaps. A total of 34 pregnant women diagnosed with early-onset preeclampsia and 34 healthy pregnant women were enrolled in this study. A mononuclear cell fragment from the venous blood was separated and frozen. The CD8+ and CD8- NK cell subpopulations were identified and compared to their immune checkpoint molecule expressions using multicolor flow cytometry. The serum CD226 levels were measured by ELISA. Based on our measures, the frequency of the CD8- subpopulation was significantly higher than that of the CD8+ counterpart in both the NKdim and NKbright subsets. Significantly lower CD226 surface expressions were detected in the preeclamptic group compared to healthy women in all the investigated subpopulations. However, while no difference was observed in the level of the soluble CD226 molecule between the two groups, the CD112 and CD155 surface expressions were significantly different. Our study's findings underscore the significant role of the CD8+ and CD8- NK subpopulations in the Th1-dominated immune environment. This deepens our understanding of early-onset preeclampsia and suggests that each subpopulation could contribute to the compensation mechanisms and the restoration of the immunological balance in this condition, a crucial step toward developing effective interventions.

The role of ultrasound and mitofusin-2 levels to predict pregnancy outcomes in patients with severe preeclampsia: a case-control study.

OBJECTIVE: The aim of this study was to evaluate mitofusin-2 levels and fetal Doppler ultrasonography effects in patients with severe preeclampsia. METHODS: This single-center case-control study was conducted in the gynecology service of the university hospital in Van. A total of 90 pregnant women aged 18-40 years were included in the study. Of these, 30 are normal, 30 have mild preeclampsia, and 30 are pregnant with severe preeclampsia. In this study, especially in severe preeclampsia patients, serum mitofusin-2 levels and important fetal Doppler flows such as uterine arterial pressure, umbilical arterial pressure, and 1st and 5th minute Apgar scores, birth weight, and the relationship between postnatal outcomes such as week of birth and the number of patients in the neonatal intensive care unit were investigated. RESULTS: There was a significant difference between the three groups in terms of mitofusin-2 levels, which was the highest in the group (p<0.05). Maternal serum mitofusin-2 levels were positively correlated with uterine arterial pressure (r=0.543, p=0.007), umbilical arterial pressure (r=0.238, p=0.008), diastolic blood pressure, and systolic blood pressure (p<0.001). Receiver operating characteristic curve of mitofusin-2 in predicting preeclampsia is as follows: optimal cutoff 1.6 ng/mL; area under the curve: 0.861; 95%CI: 0.786-0.917; sensitivity: 83.9%; and specificity: 70.0%, (p≤0.001). A one-unit increase in mitofusin-2 resulted in a statistically significant 4.21-fold increase in preeclampsia risk. CONCLUSION: This study recommends the use of mitofusin-2 together with fetal Doppler ultrasound findings as a reliable indicator of preeclampsia severity.

Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

Associations between first-trimester screening biomarkers and maternal characteristics with gestational diabetes mellitus in Chinese women.

Background: Gestational diabetes mellitus (GDM) can result in adverse maternal and neonatal outcomes. Predicting those at high risk of GDM and early interventions can reduce the development of GDM. The aim of this study was to examine the associations between first-trimester prenatal screening biomarkers and maternal characteristics in relation to GDM in Chinese women. Methods: We conducted a retrospective cohort study of singleton pregnant women who received first-trimester aneuploidy and preeclampsia screening between January 2019 and May 2021. First-trimester prenatal screening biomarkers, including pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin, and placental growth factor (PLGF), along with maternal characteristics, were collected for analysis in relation to GDM. Receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate variables associated with GDM. Results: Of the 1452 pregnant women enrolled, 96 developed GDM. PAPP-A (5.01 vs. 5.73 IU/L, P < 0.001) and PLGF (39.88 vs. 41.81 pg/mL, P = 0.044) were significantly lower in the GDM group than in the non-GDM group. The area under the ROC curve of combined maternal characteristics and biomarkers was 0.73 (95% confidence interval [CI] 0.68-0.79, P < 0.001). The formula for predicting GDM was as follows: P = 1/[1 + exp (-8.148 + 0.057 x age + 0.011 x pregestational body mass index + 1.752 x previous GDM history + 0.95 x previous preeclampsia history + 0.756 x family history of diabetes + 0.025 x chronic hypertension + 0.036 x mean arterial pressure - 0.09 x PAPP-A - 0.001 x PLGF)]. Logistic regression analysis revealed that higher pregestational body mass index (adjusted odds ratio [aOR] 1.03, 95% CI 1.01 - 1.06, P = 0.012), previous GDM history (aOR 9.97, 95% CI 3.92 - 25.37, P < 0.001), family history of diabetes (aOR 2.36, 95% CI 1.39 - 4.02, P = 0.001), higher mean arterial pressure (aOR 1.17, 95% CI 1.07 - 1.27, P < 0.001), and lower PAPP-A level (aOR 0.91, 95% CI 0.83 - 1.00, P = 0.040) were independently associated with the development of GDM. The Hosmer-Lemeshow test demonstrated that the model exhibited an excellent discrimination ability (chi-square = 3.089, df = 8, P = 0.929). Conclusion: Downregulation of first-trimester PAPP-A and PLGF was associated with the development of GDM. Combining first-trimester biomarkers with maternal characteristics could be valuable for predicting the risk of GDM.

Association of serum homocysteine with vitamin B12 and folate levels in women with pre-eclampsia in a tertiary health care center in Nepal.

BACKGROUND: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. METHOD: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. RESULTS: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). CONCLUSION: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia.

Association between pregnancy-related changes in serum creatinine and preeclampsia diagnosis.

BACKGROUND: Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality, affecting 2-8% of all pregnancies. Typically, the increased glomerular filtration rate of pregnancy results in a decrease in serum creatinine. It is unknown if women without the expected decrease in serum creatinine during pregnancy are more likely to be diagnosed with preeclampsia. OBJECTIVE: We sought to determine if the absence of a pregnancy-related decrease in serum creatinine was associated with the development of preeclampsia in patients deemed to be at high risk for developing preeclampsia. We hypothesized that the absence of the expected decrease in serum creatinine may be a marker of impaired renal function and therefore may be associated with increased risk of preeclampsia in this cohort. STUDY DESIGN: We conducted a retrospective cohort study of deliveries between November 2, 2017 and June 30, 2020 at a single institution. Pregnancies were included if a baseline serum creatinine (measured between one year prior to conception through 6 weeks gestation), and another serum creatinine value prior to 20 weeks of gestation were measured. Decrease in serum creatinine was defined as any decrease (at least 0.01 mg/dL) from baseline. The primary outcome was diagnosis of preeclampsia. Exclusion criteria included fetal anomalies, fetal demise, multiple gestation, or delivery prior to 20 weeks. Bivariable analyses were performed using Chi-square, ANOVA, and Student's t test. Logistic regression was used to determine odds of developing preeclampsia controlling for confounders. RESULTS: We identified 392 pregnancies that met inclusion criteria. Preeclampsia was diagnosed in 56 (14.3%) pregnancies. Patients diagnosed with preeclampsia were more likely to have a history of preeclampsia in a prior pregnancy, chronic hypertension (HTN), and diabetes. They were also more likely to have aspirin prescribed in the current pregnancy. Prevalence of advanced maternal age, multiparity, obesity, smoking, history of autoimmune disease, history of CKD, gestational HTN, or multiple pregnancy were not significantly different between patients with and without a diagnosis of preeclampsia. After controlling for confounders, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia (OR 0.76, CI 0.32-1.78). CONCLUSION: After controlling for risk factors associated with preeclampsia, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia in this high-risk cohort.

Are vitamin D intake and serum levels in the mid-trimester of pregnancy associated with preeclampsia? Results from a Brazilian multicentre cohort.

OBJECTIVE: To explore the association between serum levels and food intake of Vitamin D (VD) among healthy women in mid-pregnancy and preeclampsia. STUDY DESIGN: In a Brazilian multicentre cohort of healthy nulliparous pregnant women from five maternity centres we developed a nested case-control analysis comparing cases with and without preeclampsia. Women were enrolled and followed during prenatal care, including only singleton pregnancies, without any fetal malformations or previous chronic maternal disease. We matched 87 cases of preeclampsia to eligible controls randomly selected in a 1:1 ratio, by age and region. MAIN OUTCOME MEASURES: Blood samples from these were collected, and a 24-hour recall of food intake was obtained in mid-pregnancy, between 19 and 21 weeks. VD serum levels (25-hydroxyvitamin D) were measured by liquid chromatography-tandem mass spectrometry and were categorized as deficient, insufficient, and sufficient. The dietary intake of VD was estimated with the 24-hour diet recall applied at the same time and from supplementation. Maternal characteristics and VD levels were compared between cases and controls with OR and respective 95 %CI. Multivariate analysis using the Path method was used to assess relationships among VD, PE, BMI, skin colour/ethnicity, and diet. RESULTS: The maternal characteristics of both groups were similar, except for the higher occurrence of obesity among women with preeclampsia (OR 3.47, 95 %CI 1.48-8.65). Dietary intake of VD was similar in both groups, and most of the women in both groups consumed insufficient VD (82.2 vs 79.3 % in the groups with and without PE). CONCLUSIONS: Levels and dietary intake of VD were not associated with PE in this Brazilian sample of healthy pregnant women; however, BMI and skin colour/ethnicity were associated with PE.

A study on the mediating role of serum hormones in the effects of heavy metals on preeclampsia.

Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), ß-human chorionic gonadotropin (ß-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, ß-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, ß-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE.

[Preliminary exploration of the clinical warning value of ischemic modified albumin in the development of pre-eclampsia].

Objective: To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity. Methods: A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE. Results: (1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference (F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant (F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure (r=0.279), mean arterial pressure (r=0.212), and urinary protein quantification (r=0.277), while the severe PE manifestations negatively correlated include HSA levels (r=-0.644) and newborn birth weight (r=-0.305), all of which were significantly correlated (P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95%CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95%CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions: The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

Biochemical and Oxidative Biomarkers in Preeclampsia.

OBJECTIVE: To determine the biochemical and oxidative stress parameters as biomarkers in preeclampsia. STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Departments of Obstetrics / Gynaecology and Biochemistry, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from September 2022 to February 2023. METHODOLOGY: Women with preeclampsia were selected based on blood pressure exceeding 140/90 mmHg and proteinuria levels exceeding 300 mg/24 hours or showing a +1 on a dipstick test. Normotensive pregnant women were selected as controls. Venous blood was taken and centrifuged, and routine biochemical methods were used to estimate serum lipid profile levels and minerals. The estimation of oxidative stress enzymes was carried out manually using special chemicals. Student's t-test and Pearson's correlation were applied to analyse the result. RESULTS: The study included 228 subjects: 114 preeclampsia patients and 114 normal pregnant women as controls. The mean systolic blood pressure was measured at 166.25 mmHg and the diastolic blood pressure was 92.80 mmHg (p <0.001). All lipid profile estimations showed notable abnormalities, but the mean level of triglycerides (TGs) (214.90 ± 15.59 mg/dl) in preeclamptic patients was significantly elevated (p <0.05). In terms of minerals, all were deranged but magnesium (1.37 ± 0.35 mg/dl) and calcium (7.55 ± 0.45 mg/dl) were significantly decreased (p <0.05). All oxidative enzyme levels were increased (p <0.05) but malondialdehyde (MDA) with a mean level of 2.58 ± 0.40 nmol/ml was significantly elevated. The Pearson's correlation of these parameters with blood pressure also showed a positive association. CONCLUSION:  Total cholesterol triglyceride in the lipid profile, calcium and magnesium in minerals, and MDA in oxidative parameters were markedly deranged and exhibited significant associations with the severity of the disease, so could be used as disease biomarkers of preeclampsia. KEY WORDS: Preeclampsia, Gestational hypertension, Proteinuria, Lipid profile, Minerals, Oxidative stress.

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.