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1.
J Cell Mol Med ; 25(9): 4363-4372, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33811439

RESUMO

The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour invasion and migration, but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus. In this study, we aim to explore its role in trophoblast development and placenta-related pregnancy complications and the potential mechanism. Levels of FoxO3a and its phosphorylated form (p-FoxO3a) in placental tissue from healthy pregnant women and pre-eclampsia patients were first compared. Then, HTR-8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit-8, wound-healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT-PCR and ChIP-qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p-FoxO3a was increased in pre-eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule-1 (ICAM1) gene in ChIP assays and led to reduced invasion and migration of trophoblast cells, arrested cell cycle in G1 phase and increased apoptosis under oxidative stress. Our results suggested that FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.

2.
BMC Pregnancy Childbirth ; 21(1): 279, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832462

RESUMO

BACKGROUND: Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth. METHODS: A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. RESULTS: The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency. CONCLUSIONS: Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.

3.
Prenat Diagn ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720417

RESUMO

OBJECTIVE: Twin-twin transfusion syndrome (TTTS) causes perinatal mortality and morbidity in monochorionic twins. The early recognition of and interventional therapy for TTTS is associated with a more favorable overall prognosis. However, the prediction by the use of ultrasound in the first trimester has relatively poor sensitivity and specificity. This study aimed to identify metabolic biomarkers to aid in ultrasound screening of TTTS. METHODS: Maternal plasma was prospectively collected between 11 and 15 weeks of gestation in apparently uncomplicated monochorionic-diamniotic twin pregnancies. This cohort was divided into: (i) patients who were subsequently diagnosed with TTTS by using ultrasound; (ii) uncomplicated matched controls. Metabolome was profiled by using gas chromatography-mass spectrometry. RESULTS: The levels of fatty acids, organic acids, oxaloacetic acid, and beta-alanine were significantly lower in the TTTS maternal plasma at 11-15 weeks of gestation, and methionine and glycine were also higher (p < 0.05, FDR<0.12). Generally, in TTTS pregnancies, the metabolisms of amino acid, carbohydrate, cofactors, vitamins, and purine were "down-regulated"; whereas bile secretion and pyrimidine metabolism were "upregulated." CONCLUSIONS: The metabolomics scanning of early gestation maternal plasma may identify those pregnancies that subsequently develop TTTS; in particular, downregulated fatty acid levels may be biologically plausible to be implicated in the pathogenesis of TTTS.

4.
Diabetes Care ; 44(5): 1091-1099, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33782086

RESUMO

OBJECTIVE: Better preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited. RESEARCH DESIGN AND METHODS: This double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18-38 years planning conception. We investigated whether a nutritional formulation containing myo-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test). RESULTS: Between 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified P < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (ß [95% CI] loge mmol/L intervention vs. control -0.004 [-0.018 to 0.011], 0.025 [-0.014 to 0.064], 0.040 [0.004-0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92-1.62]), birth weight (adjusted ß = 0.05 kg [-0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted ß = 0.20 [-0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22-0.82]), adjusting for prespecified covariates. CONCLUSIONS: Supplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth.

5.
Clin Nutr ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33640207

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy and leads to an altered metabolic profile of human breast milk (HBM). The association between HBM metabolites and neonatal growth in GDM pregnancies has not been thoroughly investigated. AIMS: The primary aim was to quantify differences in the HBM metabolome between normal and GDM pregnancies. The secondary aim was to identify metabolites associated with neonatal growth during the first year postpartum. METHODS: In the present study, mothers intending to exclusively breastfeed (BF) and their newborns (mother-infant pairs) were recruited at delivery (n = 129 normal pregnancies and n = 98 GDM pregnancies). HBM samples (colostrum, transition milk, and mature milk) from mothers with normal pregnancies (n = 50) and GDM pregnancies (n = 50) were subjected to metabolomic profiling via liquid chromatography tandem mass spectrometry (LC-MS/MS). Receiver operating characteristic (ROC) analysis revealed the metabolomic fingerprints of GDM-associated mature HBM. Correlations between metabolites and neonatal body weight gain (BWG) were evaluated by Spearman correlation analysis. RESULTS: In total, 620 metabolites were identified in each HBM sample; 253 compounds had the same variation patterns, whereas 38 compounds had significantly different pattern transitions between the GDM and normal groups. Moreover, 12, 49 and 28 metabolites exhibited significant differences in the 3 milk types between the 2 groups. Twenty-two metabolites were confirmed by ROC analysis as metabolomic fingerprints in the mature BM of GDM patients. Ten compounds were significantly negatively correlated with neonatal growth, and only 2 unsaturated lipids (eicosatrienoic acid (FA 20:3) and lysophosphatidylcholine (LysoPC) (22:6)) were positively correlated with neonatal BWG. CONCLUSIONS: GDM is associated with alterations in the HBM metabolome. Only a small subset of compounds are associated with neonatal body weight (BW). TRIAL REGISTRATION: ChiCTR-ROC-17011508. Prospectively registered on 26 May 2017 (http://www.chictr.org.cn/listbycreater.aspx).

6.
PLoS One ; 16(2): e0244916, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33626041

RESUMO

BACKGROUND: Gangliosides are a class of sphingolipids that are present in the cell membranes of vertebrates. Gangliosides influence a broad range of cellular processes through effects on signal transduction, being found abundantly in the brain, and having a role in neurodevelopment. OBJECTIVE: We aimed to assess the effects of maternal daily consumption of ganglioside-enriched milk vs non-enriched milk and a non-supplemented group of pregnant women on maternal ganglioside levels and pregnancy outcomes. DESIGN: Double-blind parallel randomized controlled trial. METHODS: 1,500 women aged 20-40 years were recruited in Chongqing (China) between 11 and 14 weeks of a singleton pregnancy, and randomized into three groups: Control-received standard powdered milk formulation (≥4 mg gangliosides/day); Complex milk lipid-enhanced (CML-E) group-same formulation enriched with complex milk lipids (≥8 mg gangliosides/day) from milk fat globule membrane; Reference-received no milk. Serum ganglioside levels were measured in a randomly selected subsample of 250 women per group. RESULTS: CML-E milk was associated with marginally greater total gangliosides levels in maternal serum compared to Control (13.02 vs 12.69 µg/ml; p = 0.034) but not to Reference group. CML-E milk did not affect cord blood ganglioside levels. Among the 1500 women, CML-E milk consumption was associated with a lower rate of gestational diabetes mellitus than control milk [relative risk 0.80 (95% CI 0.64, 0.99)], but which was not different to the Reference group. CML-E milk supplementation had no other effects on maternal or newborn health. CONCLUSIONS: Maternal supplementation with milk fat globule membrane, as a source of gangliosides, was not associated with any adverse health outcomes, and did not increase serum gangliosides compared with the non-supplemented reference group. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR-IOR-16007700). CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-16007700; www.chictr.org.cn/showprojen.aspx?proj=12972.

7.
Clin Nutr ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33610418

RESUMO

BACKGROUND & AIMS: To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. METHODS: A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference). CONCLUSIONS: Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM.

8.
Sci Rep ; 11(1): 3793, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589705

RESUMO

The prevalence of overweight and obesity amongst reproductive women has been increasing worldwide. Our aim was to compare pregnancy outcomes and infant neurocognitive development by different BMI classifications and investigate whether early pregnancy BMI was associated with risks of adverse outcomes in a Southwest Chinese population. We analysed data from 1273 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial in Chongqing, China. Maternal BMI was classified as underweight, normal weight and overweight/obese according to the Chinese, WHO Asian, and WHO European standards. For the adverse pregnancy outcomes, after adjustment for potential confounders, an underweight BMI was associated with increased risk of small for gestational age (SGA) babies, and an overweight/obese BMI was associated with increased risk of maternal gestational diabetes mellitus (GDM), caesarean section (C-section), macrosomia and large for gestational age (LGA) babies. For infant neurocognitive development, 1017 mothers and their children participated; no significant differences were seen in the Mental Development Index (MDI) or the Psychomotor Development Index (PDI) between the three BMI groups. Our findings demonstrate that abnormal early pregnancy BMI were associated with increased risks of adverse pregnancy outcomes in Chinese women, while early pregnancy BMI had no significant influence on the infant neurocognitive development at 12 months of age.

9.
FEBS J ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529475

RESUMO

Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide, impacting the long-term health of both mother and offspring. PE has long been characterized by deficient trophoblast invasion into the uterus and consequent placental hypoperfusion, yet the upstream causative factors and effective interventional targets for PE remain unknown. Alterations in the metabolism of preeclamptic placentas are thought to result from placental ischemia, while disturbances of the metabolism and of metabolites in PE pathogenesis are largely ignored. In fact, as one of the largest fetal organs at birth, the placenta consumes a considerable amount of glucose and fatty acid. Increasing evidence suggests glucose and fatty acid exist as energy substrates and regulate placental development through bioactive derivates. Moreover, recent findings have revealed that the placental metabolism adapts readily to environmental changes, altering its response to nutrients and endocrine signals; this adaptability optimizes pregnancy outcomes by diversifying available carbon sources for energy production, hormone synthesis, angiogenesis, immune activation, and tolerance, and fetoplacental growth. These observations raise the possibility that carbohydrate and lipid metabolism abnormalities play a role in both the etiology and clinical progression of PE, sparking a renewed interest in the interrelationship between PE and metabolic dysregulation. This review will focus on key metabolic substrates and regulatory molecules in the placenta and aim to provide novel insights with respect to the metabolism's role in modulating placental development and functions. Further investigations from this perspective are poised to decipher the etiology of PE and suggest potential therapies.

10.
Metabolomics ; 17(1): 5, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33398476

RESUMO

INTRODUCTION: Small for gestational age (SGA) may be associated with neonatal morbidity and mortality. Our understanding of the molecular pathways implicated is poor. OBJECTIVES: Our aim was to determine the metabolic pathways involved in the pathophysiology of SGA and examine their variation between maternal biofluid samples. METHODS: Plasma (Cork) and urine (Cork, Auckland) samples were collected at 20 weeks' gestation from nulliparous low-risk pregnant women participating in the SCOPE study. Women who delivered an SGA infant (birthweight < 10th percentile) were matched to controls (uncomplicated pregnancies). Metabolomics (urine) and lipidomics (plasma) analyses were performed using ultra performance liquid chromatography-mass spectrometry. Features were ranked based on FDR adjusted p-values from empirical Bayes analysis, and significant features putatively identified. RESULTS: Lipidomics plasma analysis revealed that 22 out of the 33 significantly altered lipids annotated were glycerophospholipids; all were detected in higher levels in SGA. Metabolomic analysis identified reduced expression of metabolites associated with detoxification (D-Glucuronic acid, Estriol-16-glucuronide), nutrient absorption and transport (Sulfolithocholic acid) pathways. CONCLUSIONS: This study suggests higher levels of glycerophospholipids, and lower levels of specific urine metabolites are implicated in the pathophysiology of SGA. Further research is needed to confirm these findings in independent samples.

11.
Diabetes Res Clin Pract ; 171: 108623, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33316314

RESUMO

AIMS: To evaluate the influence of gestational diabetes mellitus (GDM) on the perinatal outcomes of twin pregnancies and its impact on fetal growth profiles of twin offspring from 6 weeks to 12 months of corrected age. METHODS: A longitudinal cohort study was conducted among pregnant women with twins and their twin offspring. All information on perinatal outcomes and child growth trajectories from 6 weeks to 12 months of corrected age were obtained and analyzed using a general linear model and logistic regression models. RESULTS: GDM was not correlated with adverse perinatal outcomes of twin pregnancies; however, in monochorionic diamniotic (MCDA), but not dichorionic diamniotic (DCDA) twin pregnancies, GDM was correlated with gestational hypertension disorder and a fetus being small for gestational age (OR, 2.68; 95% CI 1.16-6.04 and OR, 0.35; 95% CI 0.16-0.76, respectively). In both MCDA and DCDA groups, GDM was positively associated with a higher risk of childhood overweight at 6 months of corrected age (2.32 [1.05, 5.09] and 2.00 [1.13, 3.53]). CONCLUSIONS: GDM had a greater impact on MCDA twin pregnancies in terms of maternal gestational hypertension disease and small for gestational age of newborns. Additionally, twin offspring exposed to GDM had a higher risk of being overweight at 6 months of corrected age irrespective of chorionicity. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16008203.


Assuntos
Diabetes Gestacional/fisiopatologia , China , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Estudos Longitudinais , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos , Estudos Prospectivos
12.
PLoS One ; 15(12): e0244369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370367

RESUMO

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. Accurate prediction of preeclampsia risk would enable more effective, risk-based prenatal care pathways. Current risk assessment algorithms depend on clinical risk factors largely unavailable for first-time pregnant women. Delivering accurate preeclampsia risk assessment to this cohort of women, therefore requires for novel biomarkers. Here, we evaluated the relevance of metabolite biomarker candidates for their selection into a prototype rapid, quantitative Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) based clinical screening assay. First, a library of targeted LC-MS/MS assays for metabolite biomarker candidates was developed, using a medium-throughput translational metabolomics workflow, to verify biomarker potential in the Screening-for-Pregnancy-Endpoints (SCOPE, European branch) study. A variable pre-selection step was followed by the development of multivariable prediction models for pre-defined clinical use cases, i.e., prediction of preterm preeclampsia risk and of any preeclampsia risk. Within a large set of metabolite biomarker candidates, we confirmed the potential of dilinoleoyl-glycerol and heptadecanoyl-2-hydroxy-sn-glycero-3-phosphocholine to effectively complement Placental Growth Factor, an established preeclampsia biomarker, for the prediction of preeclampsia risk in first-time pregnancies without overt risk factors. These metabolites will be considered for integration in a prototype rapid, quantitative LC-MS/MS assay, and subsequent validation in an independent cohort.


Assuntos
Biomarcadores/sangue , Metabolômica/métodos , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/diagnóstico , Adulto , Austrália , Estudos de Casos e Controles , Cromatografia Líquida , Diagnóstico Precoce , Feminino , Glicerol/sangue , Humanos , Idade Materna , Análise Multivariada , Nova Zelândia , Pré-Eclâmpsia/sangue , Gravidez , Segundo Trimestre da Gravidez/sangue , Espectrometria de Massas em Tandem
13.
Gut Microbes ; 12(1): 1-13, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33222612

RESUMO

Emerging evidence indicates that the gut microbiome can modulate metabolic homeostasis, and thus may influence the development of gestational diabetes mellitus (GDM). However, whether and how the gut microbiome and its correlated metabolites change in GDM is uncertain. Herein we compare the gut microbial compositions, and fecal and urine metabolomes, of 59 patients with GDM versus 48 pregnant healthy controls (HCs). We showed that the microbial and metabolic signatures of GDM patients were significantly different from those of HCs. Compared to HCs, the GDM subjects were characterized by enriched bacterial operational taxonomic units (OTUs) of the family Lachnospiraceae, and depleted OTUs of the families Enterobacteriaceae and Ruminococcaceae. Some altered gut microbes were significantly correlated with glucose values and fetal ultrasonography indexes. Moreover, we identified four fecal and 15 urine metabolites that discriminate GDM from HC. These differential metabolites are mainly involved in carbohydrate and amino acid metabolism. Significantly, co-occurrence network analysis revealed that Lachnospiraceae and Enterobacteriaceae bacterial OTUs formed strong co-occurring relationships with metabolites involved in carbohydrate and amino acid metabolism, suggesting that disturbed gut microbiome may mediate GDM. Furthermore, we identified a novel combinatorial marker panel that could distinguish GDM from HC subjects with high accuracy. Together our findings demonstrate that altered microbial composition and metabolic function may be relevant to the pathogenesis and pathophysiology of GDM.

14.
J Matern Fetal Neonatal Med ; : 1-8, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32722949

RESUMO

OBJECTIVES: This study aimed to identify which element of body composition measurements taken before 17th week gestation was the strongest risk factor for gestational diabetes mellitus (GDM) in Chinese pregnant women. DESIGN AND SETTING: A retrospective study was performed using data retrieved from the Electronic Medical Record database of Chongqing Health Center for Women and Children (China) from January 2014 to December 2015. PARTICIPANTS: A total of 22,223 women were included with singleton pregnancies and no preexisting diabetes who underwent bioelectrical impedance analysis (BIA) before 17 gestational weeks and 75-g OGTT at 24-28 gestational weeks. RESULTS: The prevalence of GDM from 2014 to 2015 was 27.13% (IADPSG). All indicators of BIA (total body water, fat mass, fat-free mass, percent body fat, muscle mass, visceral fat levels, proteins, bone minerals, basal metabolic rate, lean trunk mass), age, weight and body mass index (BMI) were risk factors that significantly increased the occurrence of GDM (p < .001 for all). Women older than 30 years or with a BMI more than 23, had a significantly higher GDM prevalence (34.89% and 34.77%). After adjusted covariates, visceral fat levels at the third quartile, the ORs of GDM were 1.142 (95% CI 1.032-1.263) in model I and 1.419 (95% CI 1.274-1.581) in model II used the first quartile as reference (p < .05 for both); bone minerals at the third quartile, the ORs of GDM were 1.124 (95% CI 1.020-1.238) in model I and 1.311 (95% CI 1.192-1.442) in model II (p < .05 for both). After adjusted for age, visceral fat levels and bone minerals, OR of GDM for percent body fat more than 28.77% at the third quartile was 1.334 (95% CI 1.201-1.482) in model II (p < .05 for both). CONCLUSIONS: Visceral fat levels, bone minerals and percent body fat were significantly associated with an increased risk of GDM, providing the reference ranges of visceral fat levels, bone minerals and percent body fat as predictive factors for Chinese women to estimate the risk of GDM by BIA during pregnancy.

15.
Aging (Albany NY) ; 12(14): 14019-14036, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32697764

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease that can have long-term adverse effects on the cognitive function of mothers. In our study, we explored the changes in metabolic health and cognitive function in mice of middle- and old- age after exposure to GDM, and whether metformin therapy during pregnancy provided long-term benefits. RESULTS: Mice with GDM demonstrated significant cognitive impairment in old age, which was associated with insulin resistance. Gestational metformin therapy was shown to increase insulin sensitivity and improve cognition. The ovarian aging rate was also accelerated in mice exposed to GDM during pregnancy, which may be related to fatty acid metabolism in the ovaries. CONCLUSION: Treatment with metformin during pregnancy was shown to improve fatty acid metabolism in ovarian tissues. METHOD: During pregnancy, mice were fed with a high-fat diet (GDM group) or a low-fat diet (Control group), and a third group received metformin while receiving a high-fat diet (Treatment group). At 12 months old, the mice completed an oral glucose tolerance test, insulin tolerance test, Morris water maze test, female sex hormones were measured, and metabolite profiles of tissue from the ovaries, hypothalamus, and pituitary glands were analysed using gas chromatography-mass spectrometry.

16.
Biol Reprod ; 103(4): 866-879, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32582940

RESUMO

Fetal growth restriction (FGR) is a condition in which a newborn fails to achieve his or her prospective hereditary growth potential. This condition is associated with high newborn mortality, second only to that associated with premature birth. FGR is associated with maternal, fetal, and placental abnormalities. Although the placenta is considered to be an important organ for supplying nutrition for fetal growth, research on FGR is limited, and treatment through the placenta remains challenging, as neither proper uterine intervention nor its pathogenesis have been fully elucidated. Yes-associated protein (YAP), as the effector of the Hippo pathway, is widely known to regulate organ growth and cancer development. Therefore, the correlation of the placenta and YAP was investigated to elucidate the pathogenic mechanism of FGR. Placental samples from humans and mice were collected for histological and biomechanical analysis. After investigating the location and role of YAP in the placenta by immunohistochemistry, we observed that YAP and cytokeratin 7 have corresponding locations in human and mouse placentas. Moreover, phosphorylated YAP (p-YAP) was upregulated in FGR and gradually increased as gestational age increased during pregnancy. Cell function experiments and mRNA-Seq demonstrated impaired YAP activity mediated by extracellular signal-regulated kinase inhibition. Established FGR-like mice also recapitulated a number of the features of human FGR. The results of this study may help to elucidate the association of FGR development with YAP and provide an intrauterine target that may be helpful in alleviating placental dysfunction.

17.
Sci Rep ; 10(1): 9422, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32523012

RESUMO

Infant adiposity may be related to later metabolic health. Maternal metabolite profiling reflects both genetic and environmental influences and allows elucidation of metabolic pathways associated with infant adiposity. In this multi-ethnic Asian cohort, we aimed to (i) identify maternal plasma metabolites associated with infant adiposity and other birth outcomes and (ii) investigate the maternal characteristics associated with those metabolites. In 940 mother-offspring pairs, we performed gas chromatography-mass spectrometry and identified 134 metabolites in maternal fasting plasma at 26-28 weeks of gestation. At birth, neonatal triceps and subscapular skinfold thicknesses were measured by trained research personnel, while weight and length measures were abstracted from delivery records. Gestational age was estimated from first-trimester dating ultrasound. Associations were assessed by multivariable linear regression, with p-values corrected using the Benjamini-Hochberg approach. At a false discovery rate of 5%, we observed associations between 28 metabolites and neonatal sum of skinfold thicknesses (13 amino acid-related, 4 non-esterified fatty acids, 6 xenobiotics, and 5 unknown compounds). Few associations were observed with gestational duration, birth weight, or birth length. Maternal ethnicity, pre-pregnancy BMI, and diet quality during pregnancy had the strongest associations with the specific metabolome related to infant adiposity. Further studies are warranted to replicate our findings and to understand the underlying mechanisms.


Assuntos
Adiposidade/fisiologia , Biomarcadores/sangue , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Adulto , Peso ao Nascer/fisiologia , Índice de Massa Corporal , Dieta/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Obesidade/sangue , Obesidade/fisiopatologia , Gravidez , Estudos Prospectivos , Pregas Cutâneas
18.
Sci Rep ; 10(1): 8508, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444773

RESUMO

Preterm birth is the major contributor for neonatal and under-five years mortality rates and also accounts for a short- and long-term adverse consequences up to adulthood. Perinatal outcomes may vary according to lots of factors as preterm subtype, late prematurity, which account for the vast majority of cases, country and population characteristics. An under-recognition of the perinatal outcomes and its associated factors might have underpowered strategies to provide adequate care and prevent its occurrence. We aim to estimate the frequency of maternal and perinatal outcomes in women with different categories of preterm and term births, factors associated with poorer perinatal outcomes and related management interventions. A multicentre prospective cohort in five maternities in Brazil between 2015 and 2018. Nulliparous low-risk women with singletons were included. Comprehensive data were collected during three antenatal visits (at 19-21weeks, 27-29 weeks and 37-39 weeks). Maternal and perinatal outcomes were also collected according to maternal and neonatal medical records. Women who had spontaneous (sPTB) and provider-initiated (pi-PTB) preterm birth were compared to those who had term birth. Also, late preterm birth (after 34 weeks), and early term (37-38 weeks) were compared to full term birth (39-40 weeks). Bivariate analysis estimated risk ratios for maternal and adverse outcomes. Finally, a multivariate analysis was conducted to address factors independently associated with any adverse perinatal outcome (APO). In total, 1,165 women had outcome data available, from which 6.7% had sPTB, 4.0% had pi-PTB and 89.3% had a term birth. sPTB and pi-PTb were associated with poorer perinatal outcomes, as well as late sPTB, late pi-PTB and early term neonates. pi-PTB (RRadj 8.12, 95% CI [2.54-25.93], p-value 0.007), maternal weight gain between 20 and 27 weeks

Assuntos
Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Nascimento Prematuro/epidemiologia , Nascimento a Termo/fisiologia , Adulto , Brasil/epidemiologia , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Paridade , Gravidez , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
19.
PLoS One ; 15(5): e0232664, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401767

RESUMO

OBJECTIVE: To assess the incidence and risk factors for hyperglycemia in pregnancy in a cohort of Brazilian nulliparous pregnant women. MATERIALS AND METHODS: This is a secondary analysis of a multicenter cohort study that enrolled 1,008 nulliparous pregnant women at 19-21 weeks. Exclusion criteria included chronic exposure to corticosteroids and previous diabetes. Bivariate and multivariate analyses by Poisson regression were used to identify associated factors. RESULTS: The incidence of hyperglycemia in pregnancy was 14.9% (150/1,008), and 94.7% of these cases were gestational diabetes mellitus (142/150). Significant associated factors included a family history of diabetes mellitus, maternal overweight or obesity at enrollment, and previous maternal conditions (polycystic ovarian syndrome, thyroid dysfunctions and hypertensive disorders). A BMI ≥ 26.3Kg/m2 (RRadj 1.87 [1.66-2.10]) and a family history of diabetes mellitus (RRadj 1.71 [1.37-2.15]) at enrollment were independent risk factors for HIP. CONCLUSIONS: A family history of diabetes mellitus and overweight or obesity (until 19-21 weeks of gestation) may be used as selective markers for HIP in Brazilian nulliparous women. Given the scarcity of results in nulliparous women, our findings may contribute to determine the optimal diagnostic approach in populations of similar socioeconomic characteristics.


Assuntos
Diabetes Gestacional/epidemiologia , Hiperglicemia/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Brasil/epidemiologia , Feminino , Humanos , Incidência , Sobrepeso/epidemiologia , Gravidez , Fatores de Risco , Adulto Jovem
20.
Eur J Obstet Gynecol Reprod Biol ; 250: 250-252, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32466867

RESUMO

BACKGROUND: Since the first report of the new coronavirus (COVID-19) infection in December of 2019, it has become rapidly prevalent and been declared as a Public Health Emergency of International Concern by the World Health Organization. There are quite a few cases reported involving delivery with COVID-19 infection, but little valuable suggestion was provided about what healthcare providers of obstetrics and neonatology should do in their clinic practice for unknown status or presumed negative women. Here, we summarized the current practice of delivery management in China that successfully prevented rapid increase in adverse pregnancy outcomes and nosocomial infection in departments of obstetrics and neonatology during the pandemic of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Unidade Hospitalar de Ginecologia e Obstetrícia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Infecções por Coronavirus/virologia , Infecção Hospitalar/virologia , Parto Obstétrico/normas , Feminino , Humanos , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia
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