Maternal prepregnancy body mass index, gestational weight gain, and allergic diseases in children: A systematic review and meta-analysis.

Several studies have investigated a link between maternal preconception body mass index, gestational weight gain (GWG), and the risk of childhood allergic diseases, but the conclusions of these studies were inconsistent. This review aimed to evaluate the relationship based on existing studies. We eventually included 18 cohort studies. The findings indicated that both maternal preconception overweight or obesity increased the risk of childhood wheezing (overweight: risk ratio (RR) 1.09, 95% confidence interval (CI) 1.04-1.15; obesity: RR 1.24, 95% CI 1.12-1.38) and asthma (overweight: RR 1.18, 95% CI 1.05-1.32; obesity: RR 1.34, 95% CI 1.13-1.58), and the risk of childhood wheezing increased with continuous prepregnancy BMI changes (per 5 kg/m2 increase) (RR 1.10, 95% CI 1.05-1.15). Preconception underweight may elevate the risk of childhood eczema ever (RR 1.05, 95% CI 1.02-1.09) and current eczema (RR 1.20, 95% CI 1.05-1.37), and preconception overweight may reduce the risk of childhood eczema ever (RR 0.98, 95% CI 0.96-0.99). No statistically significant association between GWG and the risk of allergic diseases in children was found. Preconception weight management is encouraged for the prevention of allergic diseases in children.

Effects of sirtuin 1 deficiency on trophoblasts and its implications in the pathogenesis of pre-eclampsia.

BACKGROUND: Sirtuin 1 (SIRT1) is mainly localised in syncytiotrophoblasts and cytotrophoblasts, and is involved in pregnancy regulation. However, data on the association between SIRT1 and pre-eclampsia (PE) remains limited. This study aimed to investigate the role of SIRT1 in PE pathophysiology. METHODS: Placental SIRT1 expression, as well as serum SIRT1, placental growth factor (PlGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) levels, were measured using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assays in 40 healthy pregnant women (NP group) and 40 women with severe PE (PE group). Additionally, the effects of SIRT1 on the migration, invasion, PlGF, and sFlt-1 secretion of HTR-8/SVneo cells were analysed. RESULTS: SIRT1 expression was significantly reduced in the placenta of patients with severe PE compared with that in healthy pregnant women. Compared with the NP group, serum SIRT1 and PlGF expression was significantly lower in the PE group; however, the expression of serum sFlt-1 was significantly higher in the PE group. Correlation analysis showed that in the PE group, placental SIRT1 protein levels positively correlated with serum PlGF levels (r = 0.468, P = .002) and negatively correlated with serum sFlt-1 levels (r = -0.542, P < .001). Cells with downregulated SIRT1 had a significantly shorter migration distance and a prominently reduced number of invasive cells compared with the corresponding negative control group, suggesting that SIRT1 deficiency may inhibit the migration and invasive ability of HTR-8/SVneo cells. The opposite results were observed after transfection with lentivirus overexpressing SIRT1. Compared with the corresponding controls, cells with downregulated SIRT1 had significantly reduced PlGF levels and significantly increased sFlt-1 levels in the cell culture supernatants, whereas SIRT1 overexpression produced the opposite results. CONCLUSIONS: SIRT1 deficiency may contribute to the pathogenesis of pre-eclampsia by reducing trophoblastic migration, invasion, and PlGF secretion and increasing sFlt-1 secretion.

Pre-eclampsia is a serious obstetric disorder that begins in the placenta and can occur midway through pregnancy. However, its exact disease process remains unknown. During early pregnancy, trophoblasts (cells that differentiate from fertilised eggs) evolve into new blood vessels that supply oxygen and nutrients to the placenta and maintain placental formation. In people with pre-eclampsia, problematic trophoblasts lead to abnormal placental formation and release of sFlt-1 and PlGF into the mother's blood, damaging blood vessels. Experts reported that the intracellular enzyme SIRT1 might be associated with developing pre-eclampsia. SIRT1 expression in the placenta of pregnant women with pre-eclampsia was lower than normal, and the decrease in SIRT1 levels in HTR-8/Svneo trophoblasts prevented their ability to form blood vessels and altered sFlt-1 and PlGF secretion. Hence, our findings suggest that reduced SIRT1 in trophoblasts may lead to pre-eclampsia by affecting their ability to form placental blood vessels and altering enzyme secretion.

Necroptosis in the pathophysiology of preeclampsia.

Necroptosis is a newly-identified form of gene-regulated cell necrosis that is increasingly considered to be a pathway associated with human pathophysiological conditions. Cells undergoing necroptosis exhibit necrotic phenotypes, including disruption of the plasma membrane integrity, organelle swelling, and cytolysis. Accumulating evidence suggests that trophoblast necroptosis plays a complex role in preeclampsia (PE). However, the exact pathogenesis remains unclear. Its unique mechanisms of action in various diseases are expected to provide prospects for the treatment of PE. Therefore, it is necessary to further explore its molecular mechanism in PE in order to identify potential therapeutic options. This review examines the current knowledge regarding the role and mechanisms of necroptosis in PE and provides a theoretical basis for new therapeutic targets for PE.

[Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Predicting Preeclampsia During Pregnancy].

Objective: To investigate the changes of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in women with normal pregnancy women and pregnant women with preeclampsia (PE) and the value of using NLR and PLR in the first trimester to predict PE. Methods: We retrospectively collected the clinical data of 485 pregnant women (97 had PE and 388 were of normal pregnancy) who were admitted to West China Second University Hospital and had their babies delivered there between January 1 and December 31, 2016 and 30 healthy women who were not pregnant and who had physical examination at the hospital over the same period. The subjects' NLR and PLR were calculated and compared. Logistic regression analysis was done to study the risk factors of PE, and the receiver operating characteristic curves were used to assess the value of using NLR and PLR in the first trimester to predict PE. Results: There was no significant difference in NLR or PLR between the PE group and the normal pregnancy group in the first, second and third trimesters. Compared with that of the normal non-pregnant group, the NLR of the PE group and the normal pregnancy group started to rise in the first trimester, reached the maximum in the second trimester, and decreased in the third trimester; PLR started to decrease in the second trimester and reached the lowest level in the third trimester, exhibiting significant differences ( P<0.05). In the three trimesters, NLR and PLR were not associated with the severity of PE, maternal age, or pre-pregnancy BMI. The predictive model combining factors including pre-pregnancy obesity, advanced maternal age, and nulliparity showed an area under the curve ( AUC) of 0.84 for predicting PE. When NLR in the first trimester or PLR in the first trimester were added to the combined model of pre-pregnancy obesity, advanced maternal age, and nulliparity, the AUC subsequently derived were both 0.85. Conclusion: NLR and PLR are not independent influencing factors of PE and cannot improve the predictive value for PE.

SIRT3 deficiency affects the migration, invasion, tube formation and necroptosis of trophoblast and is implicated in the pathogenesis of preeclampsia.

INTRODUCTION: Sirtuin 3 (SIRT3) plays a key role in many diseases by regulating cell necroptosis and biological behavior. However, the exact role of SIRT3 in preeclampsia remains unclear. METHODS: The expression of SIRT3 and necroptosis biomarkers, including receptor-interacting protein kinase 1 (RIPK1), RIPK3 and phosphorylated mixed lineage kinase domain-like protein (p-MLKL), in the placentas of 20 healthy pregnancy controls and 20 preeclampsia patients was evaluated by immunofluorescence, quantitative real-time PCR and Western blot. The effect of hypoxia on trophoblast necroptosis was examined in HTR8/SVneo cells. The effects of SIRT3 on the necroptosis, invasion, migration, and tube formation of HTR8/SVneo cells were investigated by transfection with siRNA lentiviruses that silenced or overexpressed SIRT3. RESULTS: The expression of SIRT3 was decreased and the expression of RIPK1, RIPK3 and p-MLKL was increased in placental trophoblasts from preeclampsia patients compared to those from healthy pregnancy controls. Hypoxia increased RIPK1, RIPK3 and p-MLKL expression in HTR8/SVneo cells, while necrostatin-1 pretreatment reduced RIPK1, RIPK3 and p-MLKL expression in HTR8/SVneo cells under hypoxia. SIRT3 silencing increased RIPK1, RIPK3 and p-MLKL expression and inhibited the invasion, migration, and tube formation of HTR8/SVneo cells under hypoxia. SIRT3 overexpression produced the opposite results. DISCUSSION: We report that SIRT3 deficiency may be involved in the pathogenesis of preeclampsia by increasing necroptosis and causing abnormal trophoblastic biological behavior. The underlying mechanisms need further study.

Adipsin of the Alternative Complement Pathway Is a Potential Predictor for Preeclampsia in Early Pregnancy.

Objective: The concentrations of complement proteins (adipsin, C3a, and C5a) and soluble endoglin (sENG) in the plasma were measured in this study, and their value as early-pregnancy predictors and potential diagnostic marker of preeclampsia was assessed, respectively. Experimental Design: Plasma samples were obtained from healthy and preeclampsia pregnant women before delivery for a cross-sectional study. Plasma samples were collected from healthy and preeclampsia pregnant women throughout pregnancy and postpartum for a follow-up study. Enzyme-linked immunosorbent assays were used to detect plasma levels of several complement proteins (adipsin, C3a, and C5a) and sENG. Results: The plasma levels of adipsin, C5a, and sENG were significantly increased before delivery in pregnant women with preeclampsia. During pregnancy, the plasma adipsin, C5a, and sENG levels were increased from the third trimester in healthy pregnant women; plasma adipsin levels remained stable after delivery, while C3a levels increased in the second trimester and remained stable afterward. Furthermore, levels of adipsin, C5a, and sENG were higher in preeclampsia patients at different stages of pregnancy; the C3a level presents a similar change and no difference was found in the third trimester. In the first trimester, receiver-operating curve (ROC) curve analysis showed that adipsin (AUC, 0.83 ± 0.06, P=0.001) and sENG (AUC, 0.74 ± 0.09, P=0.021) presented high value as predictors of early pregnancy. Conclusions: Adipsin is likely a novel plasma biomarker to monitor the increased risk of preeclampsia in early pregnancy. Moreover, the increased plasma levels of adipsin, C5a, and sENG before delivery may be associated with preeclampsia.

Effect of lncRNA-ATB/miR-651-3p/Yin Yang 1 pathway on trophoblast-endothelial cell interaction networks.

Our previous studies have confirmed that lncRNA-ATB may be involved in the pathogenesis of preeclampsia, however, it is uncertain whether lncRNA-ATB influence the interaction between trophoblast and endothelial cells, which is crucial to the uterine spiral artery remodelling. Scratch wound healing and transwell invasion assay were conducted to test the migration and invasion of trophoblast cells. Co-culture model was used to simulate the physiological environment in vivo. The expression levels of lncRNA-ATB were analyzed in placenta tissues from healthy pregnant women and preeclampsia patients. Subsequently, the binding site of lncRNA-ATB and miR-651-3p was verified using dual-luciferase reporter assay, and the rescue experiment was used to study the effects of these two on the biological function. The direct effects of miR-651-3p and Yin Yang 1 (YY1) were verified using similar methods. LncRNA-ATB was found to be down-regulated in the placenta of preeclampsia patients. LncRNA-ATB knockdown decreased trophoblast migration, invasion and colocalisation with human umbilical vein endothelial cells. MiR-651-3p was a direct target of lncRNA-ATB and they had opposite effects. Moreover, the expression of lncRNA-ATB and miR-651-3p in placental tissues was negatively correlated. MiR-651-3p has been confirmed to directly target the 3' untranslated region of YY1. The inhibitory effects of YY1 low expression on biological function was rescued by miR-651-3p depletion. Western blot analysis showed that lncRNA-ATB could regulate YY1 expression by sponging miR-651-3p. LncRNA-ATB functioned as a competitive endogenous RNA of miR-651-3p to regulate YY1 on progress of spiral artery remodelling.

Macrophage-stimulating protein is decreased in severe preeclampsia and regulates the biological behavior of HTR-8/SVneo trophoblast cells.

Preeclampsia (PE) is a major challenge for obstetricians. There is no effective way to block the development of PE other than terminating the pregnancy. The biological behavior of trophoblast cells, which are similar to cancer cells, may be closely related to the onset of PE. The vital role of macrophage-stimulating protein (MSP) in the development and progression of cancer has been recognized, while a role for this protein in PE has rarely been reported. This study aimed to explore whether MSP affects severe PE (sPE) and, if so, to characterize the mechanism. Patient information, blood samples and/or placental tissues were collected. An enzyme-linked immunosorbent assay (ELISA) was used to determine the plasma MSP concentration. The relationships between the plasma MSP concentration and clinical characteristics were analyzed. Immunofluorescence was performed to localize MSP in placental tissues. Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to determine MSP protein and mRNA expression in placental tissues. MSP was overexpressed or underexpressed in the trophoblastic cell line HTR-8/SVneo by lentiviral transfection and the proliferation, apoptosis, migration, invasion and angiogenesis of cells were detected. MSP was downregulated in sPE, and the underexpression of MSP inhibited HTR-8/SVneo cell proliferation, migration, invasion and angiogenesis. We further verified that MSP affects the biological behavior of trophoblast cells through the ß-catenin/ZEB1 signaling pathway. These results suggest that decreased MSP in the blood and placental tissues of patients with sPE, especially those with early-onset sPE, leads to reduced trophoblast cell invasion, which plays an important role in the pathogenesis of PE.

Oxidative Stress From Exposure to the Underground Space Environment.

There are a growing number of people entering underground spaces. However, underground spaces have unique environmental characteristics, and little is known about their effects on human health. It is crucial to elucidate the effects of the underground space environment on the health of humans and other organisms. This paper reviews the effects of hypoxia, toxic atmospheric particles, and low background radiation in the underground space environment on living organisms from the perspective of oxidative stress. Most studies have revealed that living organisms maintained in underground space environments exhibit obvious oxidative stress, which manifests as changes in oxidants, antioxidant enzyme activity, genetic damage, and even disease status. However, there are few relevant studies, and the pathophysiological mechanisms have not been fully elucidated. There remains an urgent need to focus on the biological effects of other underground environmental factors on humans and other organisms as well as the underlying mechanisms. In addition, based on biological research, exploring means to protect humans and living organisms in underground environments is also essential.

Circulating microRNAs as biomarkers for diagnosis and prediction of preeclampsia: A systematic review and meta-analysis.

OBJECTIVE: We carried out a meta-analysis to quantitatively summarize the overall diagnostic and predictive effects of circulating microRNAs in diagnosis and prediction of preeclampsia, respectively. STUDY DESIGN: We screened selected databases and systematically retrieved articles until September 20th, 2019 for analysis. After literature screening and data extraction, we firstly conducted quality assessment according to QUADAS-2 score system. And then the pooled diagnostic and predictive parameters were calculated using a bivariate random-effect meta-analysis model. We used threshold effect analysis and subgroup analysis to identify the sources of heterogeneity. The clinical utility was validated through the Fagan's Nomogram. Sensitivity analysis was performed to assess the reliability of each included study, and we evaluated publication bias with the Deeks' funnel plot asymmetry test. RESULTS: The meta-analysis included 8 articles comprising 273 preeclampsia patients and 343 normal pregnancies. Pooled results of diagnostic values of 5 articles indicated a sensitivity of 0.88 (95 %CI: 0.80-0.93), specificity of 0.87 (95 %CI: 0.78-0.92) and diagnostic odds ratio of 50.24 (95 %CI: 21.28-118.62). The pooled sensitivity, specificity, DOR of circulating microRNAs for predicting preeclampsia of asymptomatic pregnancies were 0.61 (95 %CI: 0.55-0.68), 0.78 (95 %CI: 0.72-0.83) and 5.7 (95 %CI: 3.7-8.7) across other 3 articles. Subgroup analysis revealed that non-plasma specimen type, non-U6 reference gene and non-Asian had better diagnostic value while due to limited data, we did not conduct a subgroup analysis of predictive value. CONCLUSIONS: Circulating miRNAs distinguish patients with preeclampsia from controls with relatively high diagnostic and predictive accuracy. Then we conclude that circulating miRNAs could be a useful screening tool to diagnose and predict preeclampsia. However, its utility should be judged with caution and large-sample prospective studies are warranted to explore if its implementation improves maternal and neonatal outcomes.

The impact of particulate matter 2.5 on the risk of preeclampsia: an updated systematic review and meta-analysis.

There is increasing and inconsistent evidence of a linkage between maternal exposure to particulate matter 2.5 (PM2.5) and preeclampsia. Therefore, this study was conducted to investigate this relationship. Electronic databases including PubMed, Embase, Web of Science, and Cochrane Library were searched to identify articles published from inception to March 23, 2020, which showed a correlation between PM2.5 and preeclampsia. Finally, 9 of 523 initial studies were deemed eligible for inclusion. A random effect model was adopted to calculate the standardized odds ratio (OR) and 95% confidence interval (CI). Based on potential effect modification, subgroup analyses were further performed. Meta-analysis showed that maternal exposure to PM2.5 (per 10 µg/m3 increment) elevated the risk of preeclampsia (OR = 1.32, 95% CI 1.10 to 1.58%). Compared with other pregnancy trimesters, the third trimester of pregnancy seems to be the period in which women are more susceptible to PM2.5. Significant effect modification of the correlation between PM2.5 exposure and preeclampsia according to multiple pregnancies, pregnancy stage, maternal-related disease history, and sample size was not observed. The results demonstrated that maternal exposure to PM2.5 may predispose pregnant women to develop preeclampsia, especially in the third trimester of pregnancy. Therefore, more efforts should be made to improve air quality to maintain the health of pregnant women.

Clinical features and outcomes of pregnant women with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The recent COVID-19 outbreak in Wuhan, China, has quickly spread throughout the world. In this study, we systematically reviewed the clinical features and outcomes of pregnant women with COVID-19. METHODS: PubMed, Web of Science, EMBASE and MEDLINE were searched from January 1, 2020, to April 16, 2020. Case reports and case series of pregnant women infected with SARS-CoV-2 were included. Two reviewers screened 366 studies and 14 studies were included. Four reviewers independently extracted the features from the studies. We used a random-effects model to analyse the incidence (P) and 95% confidence interval (95% CI). Heterogeneity was assessed using the I2 statistic. RESULTS: The meta-analysis included 236 pregnant women with COVID-19. The results were as follows: positive CT findings (71%; 95% CI, 0.49-0.93), caesarean section (65%; 95% CI, 0.42-0.87), fever (51%; 95% CI, 0.35-0.67), lymphopenia (49%; 95% CI, 0.29-0.70), coexisting disorders (33%; 95% CI, 0.21-0.44), cough (31%; 95% CI, 0.23-0.39), fetal distress (29%; 95% CI, 0.08-0.49), preterm labor (23%; 95% CI, 0.14-0.32), and severe case or death (12%; 95% CI, 0.03-0.20). The subgroup analysis showed that compared with non-pregnant patients, pregnant women with COVID-19 had significantly lower incidences of fever (pregnant women, 51%; non-pregnant patients, 91%; P < 0.00001) and cough (pregnant women, 31%; non-pregnant patients, 67%; P < 0.0001). CONCLUSIONS: The incidences of fever, cough and positive CT findings in pregnant women with COVID-19 are less than those in the normal population with COVID-19, but the rate of preterm labor is higher among pregnant with COVID-19 than among normal pregnant women. There is currently no evidence that COVID-19 can spread through vertical transmission.

Laminins Regulate Placentation and Pre-eclampsia: Focus on Trophoblasts and Endothelial Cells.

Pre-eclampsia is a systemic vascular disease characterized by new-onset hypertension and/or proteinuria at ≥20 weeks of gestation and leads to high rates of maternal and perinatal morbidity and mortality. Despite the incomplete understanding of pre-eclampsia pathophysiology, it is accepted that insufficient spiral artery remodeling and endothelial dysfunction are major contributors. Laminins (LNs) are a vital family of extracellular matrix (ECM) molecules present in basement membranes that provide unique spatial and molecular information to regulate implantation and placentation. LNs interact with cell surface receptors to trigger intracellular signals that affect cellular behavior. This mini-review summarizes the role of LNs in placental development during normal pregnancy. Moreover, it describes how LN deficiency can lead to the pre-eclampsia, which is associated with trophoblast and vascular endothelial dysfunction. New research directions and the prospect of clinical diagnosis of LN deficiency are discussed, and the gaps in basic and clinical research in this field are highlighted.