Monitoring Humoral Response Following BNT162b2 mRNA Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplantation Patients: A Single-Center Prospective Study along with a Brief Review of Current Literature.

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients-mostly autologous from a single Unit-along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated-p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

Application of Biomarkers in Obese Infertile Women: A Genetic Tool for a Personalized Treatment.

This study investigates links between CART and leptin gene expression, FSH receptor Asn680Ser polymorphism, and reproductive hormones in morbidly obese patients under 40 years old, facing infertility, and undergoing bariatric surgery. A total of 29 women were included in this study. A hormonal profile along with detection of CART and leptin gene expression was evaluated before and after bariatric surgery. Additionally, the presence or absence of Asn680Ser of the FSHR gene was studied. Following bariatric surgery, a mean reduction in BMI (16.03 kg/m2) was observed in all women. FSH levels preoperatively varied significantly among genotypes, with medians of 8.1, 9.5, and 10.3 for individuals without polymorphism, heterozygotes, and homozygotes, respectively (p = 0.0408). Post surgery, marginal differences in FSH levels were observed (5.8, 7.1, and 8.2, respectively) (p = 0.0356). E2 and LH levels exhibited no significant genotype-based differences pre and post surgery. Presurgical E2 levels were 29.6, 29.8, and 29.6, respectively (p = 0.91634), while postsurgical levels were 51.2, 47.8, and 47 (p = 0.7720). LH levels followed similar patterns. Our findings highlight bariatric surgery's positive impact on BMI reduction and its potential connection to genetic markers, hormones, and infertility. This suggests personalized treatments and offers a valuable genetic tool for better fertility outcomes in obese individuals.

Maternal Blood Adipokines and Their Association with Fetal Growth: A Meta-Analysis of the Current Literature.

Background: Assessing fetal growth constitutes a fundamental aim within the realm of prenatal care. Impaired prenatal growth increases the risk of perinatal mortality, morbidity, and poor newborn outcomes. Growth restriction increases the risk of premature birth problems, as well as the risk of poor neurodevelopmental outcomes and future non-communicable disorders such as hypertension and metabolic syndrome as adults. The objective of this systematic review is to accumulate current literature evidence to assess the patterns of serum adipokine levels among women with growth-restricted fetuses and assess their potential alterations in those high-risk pregnancies. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 March 2023. All observational studies reporting serum adipokine values among women with appropriately grown and growth-restricted fetuses were held eligible. Results: The current systematic review encompassed a total of 20 studies, incorporating a patient population of 1850 individuals. Maternal blood leptin emerged as the adipokine most investigated, as evidenced by 13 studies encompassing a collective sample size of 1081 patients, all of which explored its potential correlation with intrauterine growth restriction. Elevated levels of leptin were detected in fetuses with intrauterine growth restriction, although the observed difference did not reach statistical significance. Furthermore, regarding adiponectin, the meta-analysis conducted indicated that there were not any statistically significant differences observed in the mean values of adiponectin. The available data on the remaining three adipokines were extremely limited, making it difficult for any solid conclusions to be extracted. Conclusions: Though limited and inconsistent, the existing data suggest that fetal growth restriction is not linked to leptin, adiponectin, visfatin, resistin, or RBP4. More substantial prospective studies are needed to comprehend the importance of established and novel adipokines.

Prospective Study on the Correlation between CART and Leptin Gene Expression, Obesity, and Reproductive Hormones in Individuals Undergoing Bariatric Surgery.

Obesity, a global health concern affecting 650 million individuals of all ages worldwide, prompts health complications, including fertility issues. This research investigates the impact of bariatric surgery on morbidly obese females under 40, examining the relationship between CART and leptin gene expressions and reproductive hormones. Post-surgery, a significant reduction in BMI (16.03 kg/m2, n = 29) was observed, accompanied by notable hormonal changes. FSH levels showed a mean difference of 3.18 ± 1.19 pre- and post-surgery (p < 0.001), LH levels exhibited a mean difference of 2.62 ± 1.1 (p < 0.001), E2 levels demonstrated a mean difference of 18.62 ± 5.02 (p < 0.001), and AMH levels showed a mean difference of 3.18 ± 1.19 (p < 0.001). High CART and leptin expressions before treatment correlated with lower expressions after treatment. These findings, rooted in statistically significant correlations (CART: rs = 0.51, p = 0.005; leptin: rs = 0.75, p < 0.001), shed light on potential molecular pathways connecting gene expressions with reproductive hormones post-bariatric surgery. Our study uniquely investigates the interplay between genetic markers, infertility, and bariatric surgery in women. It stands out by providing distinctive insights into the development of personalized treatment strategies for obesity-related infertility, contributing to a deeper understanding of this complex medical issue.

MicroRNAs Can Influence Ovarian Cancer Progression by Dysregulating Integrin Activity.

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

Expression of Stemness Markers in the Cervical Smear of Patients with Cervical Insufficiency.

The presence of stem cells has been previously described in human precancerous and malignant cervical cultures. Previous studies have shown a direct interplay of the stem cell niche, which is present in practically every tissue with the extracellular matrix. In the present study, we sought to determine the expression of stemness markers in cytological specimens collected from the ectocervix among women with cervical insufficiency during the second trimester of pregnancy and women with normal cervical length. A prospective cohort of 59 women was enrolled of whom 41 were diagnosed with cervical insufficiency. The expression of OCT-4 and NANOG was higher in the cervical insufficiency group compared to the control group (-5.03 (-6.27, -3.72) vs. -5.81 (-7.67, -5.02) p = 0.040 for OCT4) and (-7.47 (-8.78, -6.27) vs. -8.5 (-10.75, -7.14), p = 0.035 for NANOG. Differences in the DAZL gene were not significantly different (5.94 (4.82, 7.14) vs. 6.98 (5.87, 7.43) p = 0.097). Pearson correlation analysis indicated the existence of a moderate correlation of OCT-4 and Nanog with cervical length. Considering this information, the enhanced activity of stemness biomarkers among pregnant women diagnosed with cervical insufficiency may be predisposed to cervical insufficiency, and its predictive accuracy remains to be noted in larger population sizes.

Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications.

As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

Pre-Operative Neutrophil-to-Lymphocyte Ratio as a Predictor of Post-Operative Infectious Morbidity in Gynecologic Oncology Patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been described as a predictor of progression-free and overall survival, and in the field of peri-operative care it seems to be a factor that can help discriminate patients at risk of developing post-operative complications. In the present study we sought to determine whether NLR is useful as a biomarker in predictive models that aim to identify patients with gynecologic cancer undergoing surgery at risk of developing post-operative infectious morbidity. Patients and Methods: We designed a prospective cohort study that enrolled 208 patients with gynecologic cancer. Post-operative infectious morbidity was evaluated based on a 30-day follow-up interval from the procedure. Results: Forty-three patients (20.5%) developed post-operative infectious morbidity. Using an optimal cutoff value of 1.7 for the pre-operative NLR we observed that the sensitivity of the biomarker was 76.7% and the specificity 73.3% with a produced area under the curve of 0.760 (95% confidence interval [CI], 0.680-0.839). Univariable logistic regression indicated that NLR is a predictor of post-operative morbidity. Cox regression analysis revealed that NLR was the only factor that was associated with the timing of infectious morbidity (hazard ratio [HR], 1.339; 95% CI, 1.180-1.519; p < 0.001). Using random forest analysis and decision trees we achieved a diagnostic accuracy of the predictive model that exceeded 90%. Conclusions: Neutrophil-to-lymphocyte ratio may be a factor that could potentially help evaluate the risk of post-operative morbidity in patients with gynecologic cancer.

The effect of the delivery mode on the evolution of cervical intraepithelial lesions during pregnancy. A meta-analysis.

OBJECTIVE: The aim of the present study was to evaluate the impact of the mode of delivery on the natural evolution of cervical squamous intraepithelial lesions in pregnant patients. METHODS: Α systematic search was conducted in Medline (1966-2021), Cochrane Central Register of Controlled Trials CENTRAL (1999-2021), Scopus (2004-2021), Google Scholar (2004-2021) and Clinicaltrials.gov (2008-2021) along with the reference lists of electronically retrieved full-text papers. All the studies that investigated the correlation of the mode of delivery with the natural evolution of cervical squamous intraepithelial lesions of patients during pregnancy, were included in the present meta-analysis. RESULTS: Eight retrospective studies were finally included, comprising 813 patients whose premalignant lesions were evaluated cytologically, of whom 685 delivered via the vaginal route, and 233 patients whose squamous intraepithelial lesions were evaluated histologically, of whom 162 delivered vaginally. The methodological quality of the included studies ranged between moderate and serious. Regression rates were comparable among women that delivered with caesarean section compared to patients that delivered vaginally, both in the cytological (OR 1.32, 95% CI 0.56, 3.12) and in the histological evaluation (OR 1.87, 95% CI 0.50, 6.96) of the lesions. Subgroup analysis revealed consistent results for all subgroups of premalignant lesions. Finally, the results observed for both the persistence and the progression rates of these lesions were proportional. CONCLUSION: Our meta-analysis suggests that the delivery mode does not alter the natural evolution of squamous intraepithelial lesions in pregnant women and therefore their presence should not determine the mode of delivery.

The impact of vaginal pH on induction of labour outcomes: a meta-analysis of observational studies.

The present meta-analysis evaluates the impact of an acidic vaginal pH on the progress of labour induction with dinoprostone and misoprostol. We searched Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, Clinicaltrials.gov and Google Scholar databases for relevant studies. Meta-analysis was performed with Rstudio using the meta function and trial sequential analysis was used to evaluate the adequacy of sample size. Nine studies were retrieved that involved 809 patients. An acidic vaginal pH did not influence the efficacy of misoprostol or dinoprostone in terms of accomplishing a successful vaginal delivery (OR 0.62, 95% CI 0.29, 1.30). The interval to delivery was unaffected by the acidity of vaginal pH (Mean Difference 4.18 h, 95% CI -2.09, 10.45). In conclusion, vaginal pH does not seem to affect the potency of vaginally administered prostaglandins; therefore, moistening of vaginal tables with acetic acid does not seem reasonable until further evidence becomes available.

Serum LDH values in hypertensive disorders of pregnancy and their association with maternal and neonatal morbidity: A meta-analysis.

BACKGROUND: Serum lactate dehydrogenase has been extensively studied in hypertensive disorders of pregnancy. However, to date, its clinical usefulness in the field remains unknown. The present meta-analysis has been designed to evaluate differences in serum LDH values among patients with hypertensive disorders of pregnancy and to help determine its diagnostic accuracy as well its predictive accuracy in determining adverse pregnancy outcomes. METHODS: We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from their inception till 18 March 2021. Observational studies that assessed differences in serum LDH levels among women with hypertensive disorders of pregnancy and healthy controls were included. Meta-analysis was performed using Rstudio. Pooled mean differences (MD) were calculated with the Hartung-Knapp-Sidik-Jonkman. Meta-regression analyses, publication bias assessment and Trim and Fill function were also performed. The adequacy of the sample size was evaluated with Trial Sequential Analysis. RESULTS: Fifty-two articles were included that comprised 5340 women with hypertensive disorders of pregnancy and 2890 healthy controls. The meta-analysis revealed significant differences among patients with preeclampsia (either mild or severe) compared with controls, as well as among patients with mild and severe preeclampsia. Significant asymmetry was noted after examining funnel plots, however, and the trim and fill analysis revealed that differences were significant only among cases with severe preeclampsia and healthy controls. Morbidity outcomes increased with LDH levels >600 IU/L and particularly when these exceeded 800 IU/L. However, confidence and prediction intervals indicated an underpowered sample size for the accurate determination of the odds of developing maternal morbidity. CONCLUSION: Despite the extensive research in the field of hypertensive disorders of pregnancy, there is still lack of evidence concerning the diagnostic performance of serum LDH in clinical practice; hence, research should expand in this direction to evaluate its clinical utility.

Cephalad-caudad versus transverse blunt expansion of the low transverse hysterotomy during cesarean delivery decreases maternal morbidity: a meta-analysis.

OBJECTIVE: Cesarean delivery is the most prevalent surgical procedure worldwide, reaching approximately 29.7 million cases in 2015. It is directly associated with an increased risk of maternal and neonatal morbidity rates in the absence of malpresentation. Several techniques have been investigated, and there is evidence that cephalad-caudad expansion of the uterine incision might be associated with improved maternal outcomes compared with traditional transverse blunt expansion. The purpose of this meta-analysis was to evaluate the impact of cephalad-caudad expansion on adverse maternal outcomes, including intraoperative blood loss, risk of uterine vessel injury, and tearing of the lower uterine segment. DATA SOURCES: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials, Google Scholar, and Clinicaltrials.gov databases from inception to January 2021. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that assessed the impact of the cephalad-caudad blunt expansion of the low transverse uterine incision during cesarean delivery rather than those of transverse blunt expansion were selected for inclusion. METHODS: Effect sizes were calculated with the Hartung-Knapp-Sidik-Jonkman random-effects model in R. Trial sequential analysis was performed to evaluate the adequacy of sample sizes. RESULTS: Cephalad-caudad blunt expansion of the uterine incision was associated with a lower prevalence of unintended incision extension (relative risk, 0.62; 95% confidence interval, 0.45-0.86) and uterine vessel injury (relative risk, 0.55; 95% confidence interval 0.41-0.73). However, these complications were not accompanied by the increased need for additional suture placement (relative risk, 0.62; 95% confidence interval, 0.31-4.12) or transfusion rates (relative risk, 0.75; 95% confidence interval, 0.28-2.03). Similarly, the intraoperative duration was comparable with cases treated with transverse blunt expansion (mean difference = -0.45 minutes; 95% confidence interval -2.12 to 1.21) and the risk of intentional incision extension in the form of an inverted T (relative risk, 0.38; 95% confidence interval, 0.09-1.52). Trial sequential analysis revealed that the required sample size was reached in the unintended incision extension and uterine vessel injury outcomes. CONCLUSION: The findings of our study suggested that cephalad-caudad blunt expansion of the uterine incision is superior to transverse expansion in terms of reducing unintended incision extension and uterine vessel injury.

Galectins-1, -3, -7, -8 and -9 as prognostic markers for survival in epithelial ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Galectins are a family of proteins that have recently emerged as regulators of cancer biology. OBJECTIVES: To investigate the impact of peritumoral and tumoral galectin expression on ovarian cancer prognosis. SEARCH STRATEGY: We searched Medline, Cochrane, and EMBASE databases from inception until March 22, 2020. SELECTION CRITERIA: All studies correlating galectins and ovarian cancer prognosis were selected. DATA COLLECTION AND ANALYSIS: The literature search presented 11 studies, which contained 1034 patients. Meta-analysis was performed with RevMan 5.3 software. MAIN RESULTS: Studies were stratified into two groups depending on the location of galectin expression (peritumoral stroma or nucleus/cytoplasm of tumor cells). Tumoral galectin-7 and galectin-9 expression was significantly associated with poor overall survival (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.32-3.21, P = 0.001; OR 1.71, 95% CI 1.27-2.30, P < 0.001, respectively). The total effect of high tumoral expression of galectins in overall survival and progression-free survival was significant (OR 1.51, 95% CI 1.02-2.23, P = 0.04; OR 2.76, 95% CI 1.73-4.40, P < 0.001, respectively). CONCLUSIONS: Our results suggest that galectins are implicated in ovarian cancer prognosis; however, further research is needed to ascertain their actual importance as well as their diagnostic accuracy.

Magnesium sulfate and risk of postpartum uterine atony and hemorrhage: A meta-analysis.

OBJECTIVES: Magnesium sulfate (MgSO4) is among the most commonly used medications in labor and delivery units. It has been used as a mean to protect against eclampsia and a neuroprotective agent for fetuses at risk of preterm birth. In the present study we investigated its impact in the occurrence of postpartum uterine atony and hemorrhage. METHODS: We searched the Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, Clinicaltrials.gov and Google Scholar databases for randomized trials and observational studies. Statistical analysis was performed with the Hartung-Knapp-Sidik-Jonkman model in RStudio using the meta package. RESULTS: Twelve studies fitted the predetermined criteria and these involved 41,190 women of whom 10,565 (25.6 %) received MgSO4. The meta-analysis revealed that the risk of postpartum uterine atony was similar among patients that received MgSO4 and those that did not (OR 1.93, 95 % CI 0.78, 4.81). Estimated blood loss (SMD 0.04, 95 % CI -0.10, 0.18) as well as the risk of postpartum hemorrhage (OR 1.82, 95 % CI 0.99, 3.35) also did not differ. Subgroup analysis revealed that evidence drawn from observational studies indicates a significant effect of MgSO4 on the odds of postpartum uterine atony and hemorrhage; however, randomized trials do not support this. CONCLUSIONS: The results of our meta-analysis suggest that it is reasonable to consider MgSO4 in women at risk of delivering before the completion of its elimination half-life. However, physicians should be vigilant in cases at risk of postpartum hemorrhage as current data are very heterogeneous and should not be considered as definitive.

PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review.

INTRODUCTION: Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. METHODS: We used the Medline (1966-2020), Scopus (2004-2020), ClinicalTrials.gov (2008-2020), EMBASE (1980-2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2020), and Google Scholar (2004-2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. RESULTS: Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). CONCLUSION: Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

Maternal and neonatal outcomes following a prolonged second stage of labor: A meta-analysis of observational studies.

Several articles investigated the impact of prolonged second stage of labor on maternal and neonatal outcomes; however, strict consensus is still lacking. The purpose of the present meta-analysis is to investigate risk factors that contribute to the pathophysiology of prolonged labor as well as effect sizes of maternal and neonatal morbidity. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar database. Observational studies (prospective and retrospective) were considered eligible for inclusion in the present meta-analysis. To minimize the possibility of article losses we avoided language, country and date restrictions. Meta-analysis was performed with the RevMan 5.3 and secondary analysis with Rstudio. Overall, 13 studies were included in the present systematic review that comprised 337.845 parturient. Prolonged second stage was associated with higher odds of postpartum hemorrhage, chorioamnionitis, endometritis, postpartum fever and obstetric anal sphincter injury. Persistent occiput posterior position and shoulder dystocia were also more prevalent compared to women with normal duration of the second stage. The need for admission to the neonatal intensive care unit was higher as well as the risk of developing neonatal sepsis. On the other hand, the odds of perinatal death were comparable among cases with prolonged and normal duration of the second stage. The results of the present meta-analysis clearly indicate that deliveries following a prolonged second stage of labor are at increased risk of maternal and neonatal complications. The presented effect estimates can be used in current clinical practice during patient counseling.

Association between serum copeptin levels and preeclampsia risk: A meta-analysis.

The role of vasopressin in preeclampsia pathogenesis has been recently supported by experimental studies. This meta-analysis aims to accumulate literature evidence and evaluate whether serum copeptin levels differ among preeclamptic and healthy pregnant women. Medline, Scopus, CENTRAL, Web of Science and Google Scholar databases were systematically searched from inception. All observational studies reporting serum copeptin values among preeclamptic and healthy pregnant women were deemed eligible. Sixteen studies were included, comprising 2105 women. Preeclampsia was linked to significantly higher copeptin levels during the 1st (Standardized Mean Difference-SMD: 2.25, 95% Confidence Intervals-CI: 0.86-3.67), 2nd (SMD: 1.73, 95% CI: 0.31-3.14) and 3rd (SMD: 1.74, 95% CI: 0.96-2.53) trimester. This association was present for severe, non-severe, early and late-onset preeclampsia. Women with the severe form of the disease displayed significantly elevated copeptin levels (SMD: 1.47, 95% CI: 1.10-1.84) compared to those with the non-severe one, while no difference was evident between early and late-onset preeclampsia (SMD: -0.30, 95% CI: -0.91 to 0.31). In conclusion, the present meta-analysis suggests that preeclampsia is associated with significantly increased serum copeptin levels in all pregnancy trimesters, irrespective of disease severity and onset. Future large-scale cohort studies should confirm these findings and introduce cut-off values in order to clarify the exact accuracy of copeptin for the prediction of preeclampsia early in the course of pregnancy.

Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis.

OBJECTIVE DATA: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension. STUDY: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence. RESULTS: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery. CONCLUSION: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy.

The role of serum adipokine levels in preeclampsia: A systematic review.

BACKGROUND: Preeclampsia represents a major pregnancy complication, associated with high rates of perinatal morbidity. The aim of this systematic review is to accumulate current literature evidence in order to examine the pattern of serum adipokine levels among preeclamptic women and asses their potential efficacy in the prediction of the disease. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were systematically searched from inception. All observational studies reporting serum adipokine values among preeclamptic and healthy pregnant women were held eligible. RESULTS: A total of 163 studies were included, comprising 23,482 women. Leptin was evaluated in 91 studies and its values were found to be significantly elevated in preeclamptic women during all pregnancy trimester, independently of disease onset and severity. Preeclampsia was also associated with increased serum fatty acid binding protein-4 and chemerin levels, when measured both during the 1st and 3rd trimester. Data concerning the rest adipokines were either conflicting or limited to reach firm conclusions. Quality of evidence was evaluated to be high for leptin, moderate for serum fatty acid binding protein-4 and chemerin and low for the other adipokines. CONCLUSIONS: The existing evidence suggests that preeclampsia is linked to increased levels of leptin, chemerin and fatty acid binding protein-4 in all pregnancy trimesters and forms of the disease. Inconsistent data currently exists concerning the role of the other adipokines. Large-scale prospective studies should longitudinally evaluate the serum concentration of novel adipokines and define the optimal threshold and timing of measurement to be widely applied in clinical practice.

The role of hemoglobin degradation pathway in preeclampsia: A systematic review and meta-analysis.

INTRODUCTION: Overproduction of fetal hemoglobin by the placenta leading to increased consumption of endogenous heme scavenging proteins has been recently implicated as a novel pathway in the pathogenesis of preeclampsia. The aim of the present systematic review was to evaluate maternal serum levels of fetal hemoglobin, haptoglobin, heme oxygenase-1, hemopexin and α1-microglobulin, as well as haptoglobin phenotypes among preeclamptic and healthy pregnant women and assess their predictive role in the disease. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were systematically searched from inception. All studies comparing levels of fetal hemoglobin or heme scavengers among preeclamptic and healthy pregnant controls were deemed eligible. RESULTS: Twenty-three studies were included, with a total number of 7461 pregnant women. Quantitative synthesis was not conducted for the comparison of serum levels due to high heterogeneity. Current evidence suggests that preeclampsia is associated with increased levels of fetal hemoglobin and α1-microglobulin, as well as with lower levels of serum hemopexin. Data regarding serum haptoglobin and heme oxygenase-1 were conflicting, as the available evidence did not unanimously suggest a significant change of their levels in the disease. Network meta-analysis indicated no significant association for any of the haptoglobin phenotypes with preeclampsia development. DISCUSSION: The present review suggests that preeclampsia may be associated with increased fetal hemoglobin and α1-microglobulin and decreased hemopexin levels, although inter-study heterogeneity was high. Future large-scale studies are needed to fully elucidate the predictive efficacy of these markers by introducing cut-off values and defining the optimal gestational age for sampling.