Project description:Background and objectiveGestational diabetes mellitus (GDM) "programs" an elevated risk of metabolic dysfunctional disorders in the offspring, and has been associated with elevated leptin and decreased adiponectin levels in cord blood. We sought to assess whether docosahexaenoic acid (DHA) supplementation in GDM affects neonatal metabolic health biomarkers especially leptin and adiponectin.MethodsIn a randomized controlled trial, singleton pregnant women with de novo diagnosis of GDM at 24-28 weeks of gestation were randomized to dietary supplementation of 500 mg DHA per day (intervention, n = 30) until delivery or standard care (control, n = 38). The primary outcomes were cord blood leptin and total adiponectin concentrations. Secondary outcomes included high-molecular-weight (HMW) adiponectin and insulin-like growth factor-1 (IGF-1) concentrations in cord blood, maternal glycemic control post-intervention and birth weight (z score). In parallel, 38 euglycemic pregnant women were recruited for comparisons of cord blood biomarkers.ResultsThere were no significant differences in cord serum leptin, total and HMW adiponectin and IGF-1 concentrations between DHA supplementation and control groups (all p > 0.05). Maternal fasting and 2-h postprandial blood glucose levels at 12-16 weeks post-intervention were similar between the two groups. The newborns in the DHA group had higher birth weight z scores (p = 0.02). Cord blood total and HMW adiponectin concentrations were significantly lower in GDM vs. euglycemic pregnancies.ConclusionDocosahexaenoic acid supplementation at 500 mg/day in GDM women did not affect neonatal metabolic biomarkers including leptin, adiponectin and IGF-1. The results are reassuring in light of the absence of influence on neonatal adipokines (leptin and adiponectin), and potential benefits to fetal growth and development.Clinical trial registrationClinicaltrials.gov, NCT03569501.
Project description:OBJECTIVE: Identification of unanswered research questions about the management of gestational diabetes mellitus (GDM) is necessary to focus future research endeavors. We developed a process for elucidating the highest priority research questions on GDM. METHODS: Using a systematic review on GDM as a starting point, we developed an eight-step process: (1) identification of research gaps, (2) feedback from the review's authors, (3) translation of gaps into researchable questions using population, intervention, comparators, outcomes, setting (PICOS) framework, (4) local institutions' stakeholders' refinement of research questions, (5) national stakeholders' use of Delphi method to develop consensus on the importance of research questions, (6) prioritization of outcomes, (7) conceptual framework, and (8) evaluation. RESULTS: We identified 15 high priority research questions for GDM. The research questions focused on medication management of GDM (e.g., various oral agents vs. insulin), delivery management for women with GDM (e.g., induction vs. expectant management), and identification of risk factors for, prevention of, and screening for type 2 diabetes in women with prior GDM. Stakeholders rated the development of chronic diseases in offspring, cesarean delivery, and birth trauma as high priority outcomes to measure in future studies. CONCLUSIONS: We developed an eight-step process using a multidisciplinary group of stakeholders to identify 15 research questions of high clinical importance. Researchers, policymakers, and funders can use this list to direct research efforts and resources to the highest priority areas to improve care for women with GDM.
Project description:ObjectiveTo assess neonatal respiratory morbidity in pregnancies with and without gestational diabetes mellitus (GDM) at imminent risk of late preterm delivery in a modern U.S. cohort.MethodsSecondary analysis of a randomized placebo-controlled trial in which women with singleton pregnancies at high risk for delivery between 34 0/7 and 36 5/7 weeks of gestation were allocated to betamethasone or placebo. The primary outcome for the trial and this secondary analysis was a composite outcome of neonatal respiratory morbidity in the first 72 hours of life. Secondary outcomes included neonatal severe respiratory complications, neonatal intensive care unit (NICU) admission greater than or equal to 3 days, and hyperbilirubinemia. We examined associations between neonatal morbidities and GDM status after adjustment for baseline differences and study group allocation using modified Poisson regression. Models incorporating a product interaction term between GDM status and treatment arm (betamethasone or placebo) were also evaluated.ResultsOf the 2,831 women enrolled in the trial, 306 (10.8%) had GDM. Women with GDM were significantly older and were more likely to be parous and to have hypertensive disorders of pregnancy than those without GDM, but they were similar regarding race, gestational age at randomization (35.6 weeks) and at delivery (36.1 weeks), and study group assignment. Neonates born to women with GDM were no more likely to meet the primary outcome than those born to women without GDM, even after adjusting for differences in age, parity, and hypertensive disorders of pregnancy (12.1% vs 13.1%, adjusted RR 0.84; 95% CI 0.61-1.17), nor were they more likely to have severe respiratory complications or prolonged NICU admission.ConclusionMaternal GDM is not associated with increased neonatal respiratory morbidity in this study population who were at high risk for late preterm birth.
Project description:Background and objectives: Gestational diabetes mellitus (GDM) is known to be associated with pregnancy complications but there is limited evidence about the strength of these associations in recent clinical practice, especially after the introduction of strict guidelines for the management of pregnancies with GDM in a multidisciplinary team setting. The objectives of our study were to first compare the rates of complications in pregnancies with GDM with those that had pre-existing diabetes mellitus and those without diabetes; and second, to derive measures of effect size expressed as odds ratios after adjustment for confounding factors to assess the independent association of GDM in prediction of these pregnancy complications. Materials and Methods: This was a prospective cohort study undertaken at a large maternity unit in the United Kingdom between January 2010 and June 2022. We included singleton pregnancies that were booked at our unit at 11-13 weeks' gestation. Multivariate regression analysis was carried out to determine the risks of complications in pregnancies with GDM after adjusting for pregnancy characteristics. Risks were expressed as odds ratio (OR) (95% confidence intervals [CI]) and expressed graphically in forest plots. Results: The study population included 53,649 singleton pregnancies including 509 (1%) with pre-existing DM, 2089 (4%) with GDM and 49,122 (95%) pregnancies without diabetes. Multivariate regression analysis demonstrated that there was a significant independent contribution from GDM in the prediction of adverse outcomes, including maternal complications such as preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age neonates and elective caesarean section (CS); and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and respiratory distress syndrome. Conclusions: GDM is associated with an increased rate of pregnancy complications compared to those without diabetes, even after adjustment for maternal and pregnancy characteristics. GDM does not increase the risk of stillbirth, hypoxic ischaemic encephalopathy or neonatal death.
Project description:BackgroundGestational diabetes mellitus (GDM) significantly affects the fetal metabolic environment, elevating risks of neonatal hypoglycemia and macrosomia. Metabolomics offers promising avenues for early prediction and diagnosis of GDM and associated adverse offspring outcomes.MethodsThis study analyzed serum samples from pregnant women diagnosed with GDM at 24 to 28 weeks of gestation using untargeted metabolomics. We monitored the health outcomes of their offspring to explore the correlation between initial serum metabolite profiles and subsequent health outcomes, to uncover the predictive markers for hypoglycemia and macrosomia in these offspring.ResultsOut of 200 participants, 154 had normal newborns, 33 had offspring with hypoglycemia, and 19 had offspring with macrosomia. From 448 identified metabolites, 66 showed significant differences in cases of hypoglycemia, and 45 in macrosomia. A panel of serum metabolite biomarkers achieved Area Under the Curve (AUC) values of 0.8712 for predicting hypoglycemia and 0.9434 for macrosomia.ConclusionThe study delineated metabolic disruptions in GDM during 24-28 weeks of gestation and pinpointed biomarkers capable of forecasting adverse neonatal outcomes. These findings could inform GDM management strategies and minimize the incidence of such outcomes.
Project description:We compared the plasma miRNA expression profiles between healthy and GDM women by microarray analysis.Our study offers new insights into circulating biomarkers of GDM and thus provides a valuable resource for future investigations.
Project description:Early gestational diabetes mellitus (eGDM) is diagnosed when fasting plasma glucose before 24 weeks of gestation (WG) is ≥ 5.1 mmol/L, whilst standard GDM is diagnosed between 24 and 28 WG by oral glucose tolerance test (OGTT). eGDM seems to have worse obstetric outcomes than standard GDM. We compared the rates of postpartum glucose metabolism disorders between women with early versus standard GDM in this prospective study on women with GDM from three university hospitals between 2014 and 2016. Patients were included if they were < 24 WG with at least one risk factor for GDM and excluded if they had type 2 diabetes. Patients were assigned to Group 1 (G1) for eGDM according to IADPSG: fasting blood glucose < 24 WG between 5.1 and 7 mmol/L. Group 2 (G2) consisted of patients presenting a standard GDM at 24-28 WG on OGTT results according to IADPSG: T0 ≥ 5.1 mmol/L or T60 ≥ 10.0 mmol g/L or T120 ≥ 8.5 mmol/L. The primary outcome was postpartum OGTT result. Five hundred patients were analysed, with 273 patients undergoing OGTT at 4-18 weeks postpartum: 192 patients in G1 (early) and 81 in G2 (standard). Patients in G1 experienced more insulin therapy during pregnancy than G2 (52.2% versus 32.5%, p < 0.001), but no patients were taking insulin postpartum in either group. G1 patients experienced less preterm labour (2.6% versus 9.1%, p = 0.043), more induced deliveries (38% versus 25%, p = 0.049) and reduced foetal complications (29.2% versus 42.0%, p = 0.048). There was no significant difference in the rate of postpartum glucose metabolism disorders (type 2 diabetes, impaired glucose tolerance, impaired fasting glycaemia) between groups: 48/192 (25%) in G1 and 17/81 (21%) in G2, p = 0.58. Thus the frequency of early postpartum glucose metabolism disorders is high, without difference between eGDM and standard GDM. This supports measurement of fasting plasma glucose before 24 WG and the threshold of 5.1 mmol/L seems appropriate until verification in future studies.Trial registration: NCT01839448, ClinicalTrials.gov on 22/04/2013.
Project description:BackgroundGestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood.MethodsFour hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE.ResultsMicrobial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed.ConclusionAltogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.
Project description:BackgroundHyperglycaemic disorders of pregnancy are associated with offspring cardiovascular alterations.MethodsMySweetHeart cohort study aimed to assess the effect of maternal gestational diabetes (GDM) on offsprings' cardiovascular health. Newborns underwent clinical and echocardiographic examinations between 2016 and 2020.ResultsCompared to mothers without GDM (n = 141), mothers with GDM (n = 123) were more likely to have had GDM in previous pregnancies and had higher weight, BMI, blood glucose, and HbA1c. Newborns of both groups showed similar clinical characteristics. Echocardiography was performed on the 3rd (interquartile range, IQR, 2nd-4th) day of life in 101 offsprings of mothers without and 116 offsprings of mothers with GDM. Left ventricular (LV) mass was similar. Children born to mothers with GDM had a thicker posterior LV wall (z-score +0.15, IQR -0.38/0.62, versus +0.47, IQR -0.11/+1.1, p = 0.004), a smaller end-systolic (1.3 mL, IQR 1.0-1.5 mL, versus 1.4 mL, IQR 1.2-1.8 mL, p = 0.044) but a similar end-diastolic LV volume. They also had shorter tricuspid valve flow duration and aortic valve ejection time, lower tricuspid E-wave and pulmonary valve velocities.ConclusionsNewborns of mothers with or without GDM had similar clinical characteristics and LV mass. However, some echocardiographic differences were detected, suggesting an altered myocardial physiology among infants of mothers with GDM.RegistrationClinicalTrials.gov (NCT02872974).ImpactHyperglycaemic disorders of pregnancy are known to be associated with offspring cardiovascular alterations. Clinical characteristics and estimated left ventricular (LV) mass were similar in children issued from mothers with and without gestational diabetes (GDM). Children born to mothers with GDM had a thicker posterior LV wall and a smaller end-systolic LV volume. Although LV mass is not different, myocardial physiology may be altered in these infants. Further studies should investigate the endothelial function of this population and the cardiovascular evolution of these children over time.
Project description:Metabolic syndrome (MetS) is an established predisposing condition for type 2 diabetes mellitus (T2DM). However, it is not thoroughly evaluated whether MetS increases the risk of T2DM in women with a previous history of gestational diabetes mellitus (GDM) who already at high risk of T2DM compared with the general population. We investigated the impact of MetS on the development of postpartum diabetes in women with a history of GDM.This was a multicenter, prospective cohort study of women diagnosed with GDM. The follow-up evaluations, including the oral glucose tolerance test, were completed at 6 weeks postpartum and annually thereafter. MetS was diagnosed at the initial postpartum evaluation according to the revised criteria of the National Cholesterol Education Program-Adult Treatment Panel III. The risk of developing type 2 diabetes (T2DM) in the follow-up period was analyzed based on the presence of MetS, and the adjusted risk was calculated using a Cox proportional hazards model.A total of 412 women without diabetes at the initial postpartum evaluation participated in the annual follow-up for median 3.8 years. MetS was prevalent in 66 (19.2%) women at the initial postpartum evaluation. The incidences of diabetes in women with and without MetS were 825 and 227 per 10,000 person-years, respectively (P?<?0.001). The presence of MetS was an independent risk factor for T2DM, with a hazard ratio (HR) of 2.23 (95% confidence interval 1.04-5.08) in multivariate analysis after adjustment for clinical and metabolic parameters. When we considered MetS and impaired fasting glucose (IFG) separately, women with MetS, IFG, or both had an increased risk of T2DM, with HRs of 4.17, 4.36, and 6.98, respectively.The presence of MetS during the early postpartum period is an independent risk factor for the development of T2DM in women with a previous history of GDM.