Causal relationship association of cheese intake with gestational hypertension and diabetes result from a Mendelian randomization study

BACKGROUND The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes.AIM To determine whether cheese consumption was causally related to hypertension and diabetes during pregnancy.METHODS This was a two-sample Mendelian randomized(MR)study.Summary-level genetic data for cheese intake was exposure and corresponding outcome data for gestational hypertension and gestational diabetes were extracted from the IEU OpenGWAS database.MR analysis was conducted using inverse variance weighting.For sensitivity analyses,MR-Egger regression,weighted median,weighted mode,and leave-one-out methods were conducted.A fixed-effect model was used to meta-analyze two sample MR estimates.The traits of gestational hypertension were pregnancy hypertension(123579 individuals)and oedema,proteinuria and hypertensive disorders in pregnancy,childbirth and the puerperium(123579 individuals),and traits of gestational diabetes were gestational diabetes(123579 individuals)and diabetes mellitus in pregnancy(116363 individuals),respectively.RESULTS Cheese intake per standard deviation increase has causally reduced the risks of gestational hypertension[odds ratio(OR)=0.60,95%confidence interval(CI):0.47-0.76,P<0.001]and gestational diabetes(OR=0.41,95%CI:0.30-0.55,P<0.001)in inverse variance weighted analysis.Sensitivity analysis showed no heterogeneity(all P>0.05)nor horizontal pleiotropy(all P>0.05)in the relationship between cheese intake and gestational hypertension,but heterogeneity presented(all P<0.05)in relation to gestational diabetes in the two-sample MR analysis.CONCLUSION Cheese intake was inversely associated with gestational hypertension and gestational diabetes in MR analysis,suggesting that cheese consumption may be beneficial in preventing hypertension and diabetes during pregnancy.

Adverse Effects of Exposure to Fine Particulate Matters and Ozone on Gestational Hypertension

Gestational hypertension(GH)is a common complication during pregnancy.GH is regarded as a potential public health challenge for pregnant women and infants.Limited evidence has linked ambient air pollution to an increased GH risk.However,most of the studies were conducted in developed countries,with inconsistent results obtained.The present study was performed to explore whether exposure to particulate matters with an aerodynamic diameter≤2.5(PM2.5)and ozone(O3)was related to elevated odds of GH in a Chinese population.This population-based cohort study involved 38115 pregnant women in Wuhan,China.All information was collected from the Wuhan Maternal and Child Health Management Information System,using standardized quality control.The daily air pollutant data for PM2.5 and O3 were obtained from the 20 monitoring stations of the Wuhan Environmental Monitoring Center during 2014.The nearest monitor approach was applied to individual exposure assessment of PM2.5 and O3 for each participant.After adjusting for major confounders and other air pollutants,a 10μg/m^3 increase in PM25 and O3 concentrations was found to correlate to a 1.14-fold[95%confidence interval(95%CI):1.09,1.20]and a 1.05-fold(95%CI:1.02,1.07)increase in GH risk,respectively.Additionally,stronger relationships between GH risk and PM25 and O3 exposure were observed in women who conceived in winter and summer,respectively.These findings suggest that air pollutants may contribute to the development of GH.

Thrombin Activatable Fibrinolysis Inhibitor in Preeclmapsia and Gestational Hypertension throughout the Gestation

To clarify the role of TAFI in hypertensive disorders in pregnancy, 22 subjects, including 10 with pre-eclampsia （PE） and 12 with gestational hypertension were examined for the levels of TAFI and thrombin-antithrombin （TAT） complex. Thirty normal pregnant women served as controls. ELISA was employed for the detection. The results showed that the TAFI antigen levels in normal pregnancy group, gestational hypertension group and PE group were （85.35±24.69）%, （99.65±18.27）%, （110.12±23.36）%; （97.06±21.40）%, （114.08±27.76）%, （125.49±24.70）%; （106.6±19.21）%, （129.2±25.07）%, （139.1±30.12）%, in the 1st, 2nd and 3rd trimester respectively. No significant differences were found between the normal pregnancy group and gestational hypertension group but significant difference existed between normal pregnancy group and PE group in each trimester （P〈0.05）. TAT complexes were significantly higher in patients with PE than that in controls （P〈0.05）, but no correlation was found between TAT and TAFI. It is concluded that TAFI may contributed to the impairment of fibrinolysis in the patients with PE and may serves as a sensitive indicator for PE, but it may not help in the diagnosis of the gestational hypertension.

Impact of genetic variation of tumor necrosis factor-α on gestational hypertension

Background The mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-1α （TNF-1α） is a pro-inflammatory Th1-type cytokine. TNFA gene is located in the human leukocyte antigen （HLA） class Ⅲ region of the major histocompatibility complex （MHC） on chromosome 6. The high TNF-1α mRNA expression may be associated with the TNF2 （A） allele, which is the polymorphism of TNF-1α at position - 308 in promoter region. This study assessed whether the TNF2 （A） allele at position -308 plays a role in the alteration of blood pressure （BP） and urinary protein excretion during pregnancy. Methods The original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism （RFLP） analysis with Nco I enzyme. Results The distributions of the G/A polymorphism of TNF-1α in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 （A） allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure （P〉0.05）. The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 （A） allele compared to homozygous for the TNF1 （G） allele （systolic BE P〈0.01 and diastolic BE P〈0.05）. The elevated blood pressure in the TNF2 （A） group was accompanied by higher urinary protein excretion in the third trimester （P〈0.05）. The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters （P〉0.05）. Conclusions Maternal TNF2 （A） allele of TNF-1α promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.

Osteoprotegerin,interleukin and hepatocyte growth factor for prediction of diabetes and hypertension in the third trimester of pregnancy

BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertension(GH)in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses.Currently,the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests,and blood pressure test is usually used for the screening and diagnosis of hypertension.However,these criteria might not anticipate or detect all GDM or GH cases.Therefore,new specific predictive and diagnostic tools should be evaluated for this population.This study selected three biomarkers of osteoprotegerin(OPG),interleukin(IL)and hepatocyte growth factor(HGF)for GDM and GH predication and diagnosis.AIM To explore the feasibility of changes in placental and serum OPG,IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women.METHODS From January 2018 to January 2019,44 pregnant women with GDM and GH were selected as an observation group,and 44 healthy pregnant women were selected as a control group in the same period.Serum OPG,IL and HGF were compared between the two groups.RESULTS The levels of OPG and HGF in the observation group were lower than in the control group,and the level of IL-1βwas higher in the observation group than in the control group(all P<0.05).Furthermore,OPG and HGF were negatively associated with gestational diabetes and gestational hypertension,while IL-1βwas positively associated with GDM complicated with GH(all P<0.05).CONCLUSION The evaluation of serum OPG,HGF and IL-1βlevels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.

Screening of Biomarkers for Hypertension Susceptibility in Pregnancy

Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small molecule drug-related lncRNAs.Methods:Three patients with gestational hypertension who were treated in our hospital from May 2018 to May 2019 were selected as the research subjects and three healthy pregnant women who underwent a prenatal examination in the same hospital were selected as the control group.The placental tissues were taken from the patients.RNA-sequencing was performed to construct lncRNA/mRNA differential expression profiles;screening differentially expressed lncRNAs were used to predict target genes,and GO and KEGG enrichment analysis predicted the biological functions of target genes and the enriched signal pathways,respectively.Protein-protein interaction network,lncRNA-miRNAmRNA network,and differentially expressed genesmall molecule drug association networks were constructed.Results:RNA-seq analysis revealed 19 differentially expressed lncRNA(4 up-regulated;15 down-regulated)(P<0.05).Moreover,423 differentially expressed genes(DEGs)(84 up-regulated;339 downregulated)(P<0.05).GO and KEGG enrichment analysis found that gestational hypertension is mainly related to endothelial cell damage,inflammatory response,abnormal immune regulation,and abnormal trophoblast invasion.The PPI network and lncRNA-miRNA-mRNA network were constructed.Differentially expressed gene-drug small molecule prediction results found 19 pairs of differentially gene-small drug relationship pairs,mainly including antibody,inhibitor et al.Conclusion:Differently expressed lncRNAs in the placenta of patients with gestational hypertension can participate in the regulation of multiple biological functional levelrelated signal pathways through targeted regulation of their target genes,and play an important role in the occurrence and development of gestational hypertension.The predicted small molecule drug can be used as a reference for clinical treatment.

The relationship between physical activity in early pregnancy and hypertensive disorders of pregnancy: a cohort study in Chinese women

BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.METHODS:A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study.The pregnancy physical activity questionnaire(PPAQ)was used to assess PA,including household/caregiving,occupational,sports/exercise,and transportation activities in the first trimester of pregnancy.The diagnosis of HDP was collected,including gestational hypertension(GH)and preeclampsia(PE).Data were analyzed by unconditional multivariate logistic regression,and the odds ratio(OR)and 95%confi dence interval(CI)were calculated.RESULTS:A total of 178(2.6%)of the 6,820 women were diagnosed with HDP,of which 126(1.8%)were GH and 52(0.8%)were PE.Overall,we found no association between PA in early pregnancy and PE.A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity(MVPA)(adjusted OR 0.54,95%CI 0.31–0.96).No association was observed between PA and HDP in early pregnancy,regardless of diff erent intensities or types of PA.CONCLUSION:MVPA in the first trimester is an influencing factor of HDP.Encouraging pregnant women to engage in MVPA in the fi rst trimester may help to prevent GH.

Data Analytics on Unpredictable Pregnancy Data Records Using Ensemble Neuro-Fuzzy Techniques

The immune system goes through a profound transformation during pregnancy,and certain unexpected maternal complications have been correlated to this transition.The ability to correctly examine,diagnoses,and predict pregnancy-hastened diseases via the available big data is a delicate problem since the range of information continuously increases and is scalable.Many approaches for disease diagnosis/classification have been established with the use of data mining concepts.However,such methods do not provide an appropriate classification/diagnosis model.Furthermore,single learning approaches are used to create the bulk of these systems.Classification issues may be made more accurate by combining predictions from many different techniques.As a result,we used the Ensembling of Neuro-Fuzzy(E-NF)method to perform a high-level classification of medical diseases.E-NF is a layered computational model with self-learning and self-adaptive capabilities to deal with specific problems,such as the handling of imprecise and ambiguous data that may lead to uncertainty concerns that specifically emerge during the classification stage.Preprocessing data,Training phase,Ensemble phase,and Testing phase make up the complete procedure for the suggested task.Data preprocessing includes feature extraction and dimensionality reduction.Besides such processes,the training phase includes the fuzzification process of medical data.Moreover,training of input data was done using four types of NF techniques:Fuzzy Adaptive Learning Control Network(FALCON),Adaptive Network-based Fuzzy Inference System(ANFIS),Self Constructing Neural Fuzzy Inference Network(SONFIN)and/Evolving Fuzzy Neural Network(EFuNN).Later,in the ensemble phase,all the NF methods’predicted outcomes are integrated,and finally,the test results are evaluated in the testing phase.The outcomes indicate that the method could predict impaired glucose tolerance,preeclampsia,gestational hypertensive abnormalities,bacteriuria,and iron deficiency anaemia better than the others.In addition,the model exposed the capability to be utilized as an autonomous learning strategy,specifically in the early stages of pregnancy,examinations,and clinical guidelines for disease interventions.

Association of interpregnancy interval and risk of adverse pregnancy outcomes in woman by different previous gestational ages

Background:With an increasing proportion of multiparas,proper interpregnancy intervals(IPIs)are urgently needed.However,the association between IPIs and adverse perinatal outcomes has always been debated.This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods:We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019.Multivariable Poisson models with restricted cubic splines were used.Each adverse outcome was analyzed separately in the overall model and stratified models.The stratified models included different categories of fertility policy periods(2014-2015,2016-2017,and 2018-2019)and infant gestational age in previous pregnancy(<28 weeks,28-36 weeks,and≥37 weeks).Results:There were 781,731 pregnancies enrolled in this study.A short IPI(≤6 months)was associated with an increased risk of preterm birth(OR[95%CI]:1.63[1.55,1.71]for vaginal delivery[VD]and 1.10[1.03,1.19]for cesarean section[CS]),low Apgar scores and small for gestational age(SGA),and a decreased risk of diabetes mellitus in pregnancy,preeclampsia or eclampsia,and gestational hypertension.A long IPI(≥60 months)was associated with an increased risk of preterm birth(OR[95%CI]:1.18[1.11,1.26]for VD and 1.39[1.32,1.47]for CS),placenta previa,postpartum hemorrhage,diabetes mellitus in pregnancy,preeclampsia or eclampsia,and gestational hypertension.Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes.The estimated risk of preterm birth,low Apgar scores,SGA,diabetes mellitus in pregnancy,and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion:For pregnant women with shorter or longer IPIs,more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Iron supplementation for non-anaemic pregnant women and the incidence of hypertensive disorders in pregnancy:A systematic review and meta-analysis

Objective:To investigate effect of iron supplementation on the risk of hypertensive disorders in pregnancy in non-anaemic pregnant women.Methods:A literature search was conducted using three categories of terms with its synonyms or related words:"iron","supplement",“hypertensive disorders in pregnancy”through MEDLINE(OVID),CINAHL,PubMed,Cochrane Library,Scopus,Web of Science,ICTRP,and ClinicalTrials.gov,and manual search of references was used in seven potential resources.The inclusion criteria were randomized control trials(RCTs),published in English,full-text available,having healthy pregnant women without anaemia for study participants,and having hypertensive disorders in pregnancy at the end of pregnancy as the outcome.The risk of bias assessment tool was used for quality appraisal.Meta-analysis was conducted by calculating the fixed and random effects of the odds ratio(OR)for iron supplementation among non-anaemic pregnant women compared with the incidence of hypertensive disorders in pregnancy.The range of the study’s estimation accuracy was reflected by a 95%confidence interval(CI).Results:Four RCTs were included in the meta-analysis.The pooled results showed that iron supplementation possibly had no effect on the incidence of hypertensive disorders in pregnancy(OR 0.93,95%CI 0.81-1.07;P=0.30),gestational hypertension(OR 1.37,95%CI 0.69-2.73;P=0.36)as well as on the development of preeclampsia(OR 1.45,95%CI 0.71-2.97;P=0.31).Conclusions:Iron supplementation has no effect on the incidence of hypertension in non-anaemic pregnant women.In general,there is a lack of evidence for the association between iron supplementation and the incidence of hypertensive disorders in pregnancy among non-anaemic pregnant women,and further studies are needed.

The level of bile salt-stimulated lipase in the milk of Chinese women and its association with maternal BMI

This study aimed to investigate the bile salt-stimulated lipase(BSSL) concentration in the milk of Chinese women and its correlation with maternal body mass index(BMI), gestational diabetes mellitus(GDM) and gestational hypertensive disorder(GHD). The BSSL levels in the milk samples were measured by enzyme-linked immunosorbent assay(ELISA). BSSL level in colostrum milk of mothers with full-term infants was positively correlated with pregnancy week and negatively correlated with maternal pre-pregnancy BMI and BMI late in pregnancy. Moreover, the BSSL concentration in mature milk was positively correlated with BMI gain during pregnancy. The BSSL concentration in colostrum milk was lower in GDM mothers than in normal mothers. The BSSL helps infants digest fat in early life and its level was associated with lactation. The changes in BSSL characteristics with maternal BMI and GDM in this study may have clinical implications regarding the effects of pregnancy weight and metabolism on the nutrition and health of the offspring.

Antihypertensive drugs in pregnancy

Chronic hypertension complicates 3%-5% of pregnancies and gestational hypertension occurs in 6% of pregnancies.Preeclampsia complicates 25% of the pregnancies with chronic hypertension,and approximately 15%-45% of the patients with gestational hypertension will develop preeclampsia,a dangerous condition that harms the maternal and fetal safety.Antihypertensive medication is used to treat severe hypertension to prevent serious maternal and fetal complications,but there is no consensus on when and how to treat mild-to-moderate hypertension in pregnancy.This article reviews the usage,effect and safety of first,second and third line antihypertensive drugs for mild-to-moderate hypertension in pregnancy.

The Role of Metformin in Treating Preeclampsia

Preeclampsia(PE)is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year.Unfortunately,there is no effective management to arrest the progression of this disease unless delivery.Therefore,standardized management or preventive treatments are needed urgently.PE is closely associated with placental hypoxia,which increases the secretion of soluble fms-like tyrosine kinase 1(sFlt-1)as well as soluble endoglin(sEng)into the maternal circulation.Metformin has been found to inhibit those anti-angiogenic factors so it might be a candidate to prevent or treat PE.Women who are diagnosed with gestational diabetes mellitus(GDM)are more likely to have complications of hypertension or PE,so this review aims to demonstrate that the application of metformin in GDM might prevent the onset or progression of PE complicated with GDM.