Associations of urinary biomarkers of phthalates, phenols, parabens, and organophosphate esters with glycemic traits in pregnancy: The Healthy Start Study.

BACKGROUND: Certain endocrine-disrupting chemicals (EDCs) are widespread in consumer products and may alter glucose metabolism. However, the impact of EDC exposures on glucose and insulin regulation during pregnancy is incompletely understood, despite potential adverse consequences for maternal and infant health. We estimated associations between 37 urinary biomarkers of EDCs and glucose-insulin traits among pregnant women. METHODS: Seventeen phthalate or phthalate substitute metabolites, six environmental phenols, four parabens, and ten organophosphate ester metabolites were quantified in mid-pregnancy urine from 298 participants in the Healthy Start Study. Fasting blood glucose, insulin, and hemoglobin A1c were assessed concurrently, and Homeostasis Model Assessment 2-Insulin Resistance (HOMA2-IR) was calculated. Gestational diabetes diagnoses and screening results were obtained from medical records for a subset of participants. We estimated associations between each EDC and outcome separately using linear and robust Poisson regression models and analyzed EDC mixture effects. RESULTS: The EDC mixture was positively associated with glucose, insulin, and HOMA2-IR, although overall associations were attenuated after adjustment for maternal BMI. Two mixture approaches identified di(2-ethylhexyl) phthalate (DEHP) metabolites as top contributors to the mixture's positive associations. In single-pollutant models, DEHP metabolites were positively associated with fasting glucose, fasting insulin, and HOMA2-IR even after adjustment for maternal BMI. For example, each interquartile range increase in log2-transformed mono(2-ethyl-5-oxohexyl) phthalate was associated with 2.4 mg/dL (95% confidence interval (CI): 1.1, 3.6) higher fasting glucose, 11.8% (95%CI: 3.6, 20.5) higher fasting insulin, and 12.3% (95%CI: 4.2, 21.1) higher HOMA2-IR. Few EDCs were associated with hemoglobin A1c or with a combined outcome of impaired glucose tolerance or gestational diabetes. DISCUSSION: Exposures to phthalates and particularly DEHP during pregnancy are associated with altered glucose-insulin regulation. Disruptions in maternal glucose metabolism during pregnancy may contribute to adverse pregnancy outcomes including gestational diabetes and fetal macrosomia, and associated long-term consequences for maternal and child health.

Sleep conditions and sleep hygiene behaviors in early pregnancy are associated with gestational diabetes mellitus: A propensity-score matched study.

PURPOSE: To explore the influence of sleep conditions and sleep hygiene behaviors in early pregnancy on gestational diabetes mellitus (GDM) development. METHODS: This 1:1 propensity-score matched study included 1,216 pregnant women divided into GDM and control groups based on diagnosis via the oral glucose tolerance test at 24-28 gestational weeks. Sleep conditions and hygiene behaviors were evaluated using structural questionnaires, including the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Sleep Hygiene Practice Scale. Univariate and multivariate logistic regression analyses and Spearman's correlation were conducted to identify the associations. RESULTS: After adjusting for baseline clinical characteristics, women with GDM were more likely to have poor sleep quality (adjusted odds ratio [AOR] = 1.585, 95% confidence interval [CI]: 1.261-1.992) and higher scores for subjective sleep quality, latency, duration, efficiency, and sleep disturbances (all P < 0.01). Mild sleepiness (AOR = 1.311, 95% CI: 1.012-1.699) and worrying about not being able to fall asleep (AOR = 1.123, 95% CI: 1.005-1.255) were more likely to occur in the GDM group. Sleep quality and hygiene behaviors such as sleep-irrelevant activities, staying in bed after waking up, weekend catch-up sleep, and overeating before bedtime were significantly correlated with gestational diabetes variables. CONCLUSION: Poor sleep conditions and specific sleep hygiene behaviors in early pregnancy may be independent risk factors for GDM. This suggests that sleep assessment and behavior education can be used as new approaches for the early implementation of surveillance and prevention of GDM.

The impact of PM2.5 and its constituents on gestational diabetes mellitus: a retrospective cohort study.

BACKGROUND: There is increasing evidence that exposure to PM2.5 and its constituents is associated with an increased risk of gestational diabetes mellitus (GDM), but studies on the relationship between exposure to PM2.5 constituents and the risk of GDM are still limited. METHODS: A total of 17,855 pregnant women in Guangzhou were recruited for this retrospective cohort study, and the time-varying average concentration method was used to estimate individual exposure to PM2.5 and its constituents during pregnancy. Logistic regression was used to assess the relationship between exposure to PM2.5 and its constituents and the risk of GDM, and the expected inflection point between exposure to PM2.5 and its constituents and the risk of GDM was estimated using logistic regression combined with restricted cubic spline curves. Stratified analyses and interaction tests were performed. RESULTS: After adjustment for confounders, exposure to PM2.5 and its constituents (NO3-, NH4+, and OM) was positively associated with the risk of GDM during pregnancy, especially when exposure to NO3- and NH4+ occurred in the first to second trimester, with each interquartile range increase the risk of GDM by 20.2% (95% CI: 1.118-1.293) and 18.2% (95% CI. 1.107-1.263), respectively. The lowest inflection points between PM2.5, SO42-, NO3-, NH4+, OM, and BC concentrations and GDM risk throughout the gestation period were 18.96, 5.80, 3.22, 2.67, 4.77 and 0.97 µg/m3, respectively. In the first trimester, an age interaction effect between exposure to SO42-, OM, and BC and the risk of GDM was observed. CONCLUSIONS: This study demonstrates a positive association between exposure to PM2.5 and its constituents and the risk of GDM. Specifically, exposure to NO3-, NH4+, and OM was particularly associated with an increased risk of GDM. The present study contributes to a better understanding of the effects of exposure to PM2.5 and its constituents on the risk of GDM.

The Effect of Maternal Blood Glucose on Umbilical Cord Blood Fibrinogen in Women With Gestational Diabetes.

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM) is delineated by the presence of glucose intolerance at any level that manifests or is initially identified during pregnancy. Factor I fibrinogen is among the most essential blood coagulation proteins. The concentration of fibrinogen influences platelet aggregation and blood viscosity. This study aimed to determine the correlation between fetal cord blood fibrinogen and plasma fibrinogen in pregnant women with GDM and between fetal cord blood fibrinogen and maternal blood sugar. METHODS: A cross-sectional study was executed at Al-Elwiya Maternity Teaching Hospital in the obstetrics and gynecology department. The sample included 90 term pregnant women: 45 were confirmed to have GDM, and 45 healthy pregnant women served as control. Estimation of prelabor maternal fasting and random plasma glucose and plasma fibrinogen was performed. During delivery, blood was drawn from the umbilical cord to estimate neonatal plasma glucose and fibrinogen levels. RESULTS: The mean maternal plasma fibrinogen level exhibited a notable increase in women with GDM compared to the control (330.11 ± 56.92 mg/dl versus 254.89 ± 41.01 mg/dl). The infants of diabetic mothers had significantly lower mean cord plasma glucose levels (65.71 ± 14.63 mg/dl versus 77.80 ± 7.81 mg/dl) and higher mean cord plasma fibrinogen levels (269.42 ± 25.91 mg/dl versus 229.69 ± 21.29 mg/dl). Umbilical cord plasma fibrinogen was correlated positively with maternal plasma sugar and fibrinogen. CONCLUSION: A positive correlation between maternal and fetal cord fibrinogen levels was determined in women with GDM. Monitoring plasma fibrinogen levels in neonates of mothers with GDM could be facilitated by longitudinal, large-scale validation studies enabled by artificial intelligence as a new, evolving technique that contributes to more valuable outcomes. This would shed additional light on the course and function of plasma fibrinogen for a more comprehensive analysis of the fetal clotting system.

Enhanced recovery after surgery in elective cesarean section patients with gestational diabetes mellitus does not lead to glucose-related maternal and neonatal complications.

Objective: For elective cesarean section patients with gestational diabetes mellitus (GDM), there is a lack of evidence-based research on the use of enhanced recovery after surgery (ERAS). This study aims to compare the ERAS after-surgery protocol and traditional perioperative management. Research design and methods: In this retrospective cohort study, singleton pregnancies with good glucose control GDM, delivered by elective cesarean sections under intravertebral anesthesia at least 37 weeks from January 1 to December 31, 2022, were collected at the Third Affiliated Hospital of Sun Yat-sen University. We divided all enrolled pregnant women and newborns into an ERAS group and a control group (the traditional perioperative management group) based on their adherence to the ERAS protocol. The primary outcome was the preoperative blood glucose level, with an increase of more than 1 mmol/L indicating clinical significance when compared to the control group. The secondary outcome was centered around an adverse composite outcome that affected both mothers and newborns. Results: We collected a total of 161 cases, with 82 in the ERAS group and 79 in the control group. Although the mean preoperative blood glucose level in the ERAS group was significantly higher than in the control group (5.01 ± 1.06 mmol/L vs. 4.45 ± 0.90 mmol/L, p<0.001), the primary outcome revealed that the mean glycemic difference between the groups was 0.47 mmol/L (95% CI 0.15-0.80 mmol/L), which was below the clinically significant difference of 1 mmol/L. For the secondary outcomes, the ERAS group had an 86% lower risk of a composite adverse outcome compared to the control group. This included a 73% lower risk of perioperative maternal hypoglycemia and a 92% lower rate of neonatal hypoglycemia, all adjusted by age, hypertensive disorder of pregnancy, BMI, gestational weeks, primigravidae, primary pregnancy, GDM, surgery duration, and fasting glucose. Conclusion: Implementing a low-dose carbohydrate ERAS in pregnant women with GDM prior to elective cesarean section, compared to traditional perioperative management, does not lead to clinically significant maternal glucose increases and thus glucose-related maternal or neonatal perioperative complications.

Integrating polygenic risk scores in the prediction of gestational diabetes risk in China.

Background: Polygenic risk scores (PRS) serve as valuable tools for connecting initial genetic discoveries with clinical applications in disease risk estimation. However, limited studies have explored the association between PRS and gestational diabetes mellitus (GDM), particularly in predicting GDM risk among Chinese populations. Aim: To evaluate the relationship between PRS and GDM and explore the predictive capability of PRS for GDM risk in a Chinese population. Methods: A prospective cohort study was conducted, which included 283 GDM and 2,258 non-GDM cases based on demographic information on pregnancies. GDM was diagnosed using the oral glucose tolerance test (OGTT) at 24-28 weeks. The strength of the association between PRS and GDM odds was assessed employing odds ratios (ORs) with 95% confidence intervals (CIs) derived from logistic regression. Receiver operating characteristic curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were employed to evaluate the improvement in prediction achieved by the new model. Results: Women who developed GDM exhibited significantly higher PRS compared to control individuals (OR = 2.01, 95% CI = 1.33-3.07). The PRS value remained positively associated with fasting plasma glucose (FPG), 1-hour post-glucose load (1-h OGTT), and 2-hour post-glucose load (2-h OGTT) (all p < 0.05). The incorporation of PRS led to a statistically significant improvement in the area under the curve (0.71, 95% CI: 0.66-0.75, p = 0.024) and improved discrimination and classification (IDI: 0.007, 95% CI: 0.003-0.012, p < 0.001; NRI: 0.258, 95% CI: 0.135-0.382, p < 0.001). Conclusions: This study highlights the increased odds of GDM associated with higher PRS values and modest improvements in predictive capability for GDM.

Evaluating the diagnostic potential of gelsolin in gestational diabetes mellitus: A case-control study.

OBJECTIVES: To investigate the association between gestational diabetes mellitus (GDM) and blood levels of gelsolin (an inflammation-related protein thought to be reduced in type 2 diabetes mellitus) and to determine its role in potential diagnosis and neonatal outcomes. METHODS: This prospective case-control study was conducted at Ankara Etlik City Hospital between November 2023 and February 2024 with 40 pregnant women with GDM and 40 normoglycemic women. Pregnant women aged 18-40 years who were in their 24th to 28th week of pregnancy and had no known chronic disease were included in the present study and it was investigated as to whether there was a significant difference between the two groups in terms of gelsolin levels and neonatal outcome. RESULTS: Gelsolin level was statistically significantly lower in the GDM group than in the control group (P = 0.004). In patients with fasting blood glucose <96 mg/dL, maternal serum gelsolin levels were associated with GDM, with a cut-off of 15.38 or less, showing a sensitivity of 73%, a specificity of 67%, and an area under the curve (AUC) of 0.703 (95% confidence interval [CI] 0.576-0.810, P = 0.002). There was no difference between groups in terms of adverse obstetric outcomes, but gelsolin levels were associated with composite neonatal adverse outcome (macrosomia, Apgar score at 5 min less than 7, preterm birth, need for neonatal intensive care), with a cut-off value of 16.66 or less showing a sensitivity of 84.6%, specificity of 40.7% and AUC of 0.644 (95% CI 0.529-0.748, P = 0.031). CONCLUSION: Gelsolin could potentially serve as a promising biomarker for the diagnosis of GDM.

Patient preference of level I, II and III sleep diagnostic tests to diagnose obstructive sleep apnoea among pregnant women in early to mid-gestation.

PURPOSE: There is a paucity of data on preferences for obstructive sleep apnoea (OSA) diagnostic tests during pregnancy. Simple test completion rates fail to capture patient preference or experience of completing sleep diagnostic tests. We assessed preference, ease of use, convenience, and the repeatability of level I, II and III sleep diagnostic tests, using questionnaires, in pregnant women in early to mid-gestation. METHODS: Pregnant women with signs or symptoms of OSA, or at high risk of cardiometabolic disorders of pregnancy completed level I, II and III sleep studies by 24 weeks gestation. Participants then completed a questionnaire to rank test preference. Additional questionnaires assessed ease of use, convenience, and acceptability to repeat test, using 5-point Likert scale questions, yes/no response and optional linked text fields. RESULTS: Of fifty-two consented participants, 43 completed any questionnaire (mean age 32.7 ± 5.4 years, BMI 32.7 ± 5.4, median gestation at Level I polysomnography (PSG) of 14.2 weeks (interquartile range (IQR) 13.5-17.6)). Of the 29 respondents who completed test ranking questionnaire, level III was the preferred test ((n = 21 / 29, 75%)), followed by level 1 (n = 6 / 29, 20.7%) and level II (n = 2 / 29, 7.1%) (p for diff < 0.001). Level III was reported the easiest test (very easy to complete) (n = 16, 51.6%), followed by level I(n = 10, 33.3%), and level II (n = 9, 9.1%) (p for diff < 0.001)). Level III was reported most convenient test (very convenient to complete) (n = 16, 51.6%), followed by level I (n = 4, 13.3%) and level II (n = 4, 13.3%) (p for diff < 0.001)). Level III was reported most acceptable to repeat (very acceptable to repeat) (n = 13, 41.9%), followed by level I (n = 3, 10.0%) and level II (n = 3, 10.0%) (p for diff < 0.001)). CONCLUSION: Pregnant women being assessed for OSA by 24 weeks gestation preferred to undertake level III sleep studies and found level III easier to use, more convenient and most acceptable to repeat than Level I and II studies. Given autonomy is an important principle, patient preference of sleep diagnostic tests should be taken into consideration in sleep clinical services and research involving pregnant women.

Risk cycling in diabetes and autism spectrum disorder: a bidirectional Mendelian randomization study.

Objective: The relationship between diabetes mellitus (DM) and autism spectrum disorder (ASD) remains controversial. This study aimed to analyze the causal relationship between different types of DM and ASD by bidirectional Mendelian randomization (MR). Methods: Single nucleotide polymorphisms for type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and ASD were obtained from genome-wide association studies. Subsequently, inverse variance weighted, MR-Egger, and weighted median were used to test the exposure-outcome causality. Finally, MR-Egger's intercept, Cochran's Q, and leave-one-out method were used to assess horizontal pleiotropy, heterogeneity, and sensitivity of the results, respectively. Results: The positive analysis showed that T2DM was associated with an increased risk of ASD, whereas neither T1DM nor GDM was associated with the risk of ASD. The reverse analysis showed that ASD was associated with an increased risk of T2DM, while it was not associated with the risk of either T1DM or GDM. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05) for these results. Cochran's Q showed no heterogeneity expect for the results of T1DM on the risk of ASD, and leave-one-out sensitivity analysis showed these results were robust. Conclusion: This MR analysis suggests that T2DM and ASD are reciprocal risk factors and that they may create an intergenerational risk cycling in female patients. Aggressive prevention and treatment of T2DM and ASD help to break the trap of this risk cycling. Additionally, this study does not support a causal relationship between T1DM and ASD, as well as GDM and ASD. And more studies are needed in the future to continue to explore the interactions and underlying mechanisms between different types of DM and ASD.

Microbial Etiology, Antimicrobial Resistance, and Risk Factors of Surgical Site Infections in Gestational Diabetes Mellitus Patients Undergoing Elective Pre-Labor Cesarean Deliveries.

Background: Gestational Diabetes Mellitus (GDM) significantly increases the risk of adverse pregnancy outcomes, including elective pre-labor cesarean deliveries. Postoperative surgical site infections (SSIs) pose a significant concern, underscoring the need for a detailed investigation into their causes and preventative measures. The aim of this study is to systematically identify and analyze the microbial etiology and antimicrobial resistance profiles of pathogens responsible for SSIs in GDM patients undergoing elective pre-labor cesarean deliveries. Additionally, this research aims to elucidate the risk factors contributing to SSIs, with a specific focus on operation duration, amniotic fluid contamination, and genital tract inflammation, and their correlation with the incidence of SSIs. Methods: A retrospective analysis was conducted at our Hospital between September 2018 and July 2023, involving 150 GDM patients who underwent elective pre-labor cesarean deliveries. Patients were categorized into infected and uninfected groups based on postoperative SSIs. Clinical data were meticulously collected and analyzed using SPSS software (version 27.0). Independent sample t-tests and chi-square tests were employed for statistical analysis. Results: Microbial profiling revealed that Gram-negative bacteria, primarily E. coli, constituted approximately 59.46% of the isolated strains, exhibiting significant resistance to commonly used antibiotics such as ampicillin and cefotaxime. Elevated levels of biomarkers, including Procalcitonin (PCT) and Hemoglobin A1c (HbA1c), were significantly associated with SSIs. Multivariate logistic regression analysis identified operation time ≥1-hour, amniotic fluid contamination, and genital tract inflammation as significant risk factors. Conclusion: This study highlights the microbial etiology, resistance patterns, and risk factors for SSIs in GDM cesarean patients, emphasizing the need for tailored preoperative evaluations.

The impact of gestational diabetes and gestational hypertension on future cardiovascular events: A nationwide cross-sectional cohort study.

OBJECTIVES: Cardiovascular disease is the leading cause of female death worldwide. The link between future cardiovascular events and a history of hypertensive disease in pregnancy or gestational diabetes (GDM) has been well established. Less well understood is the impact on future cardiovascular risk when gestational hypertension (GH) and GDM have occurred together. We assessed the association of GDM and GH with future cardiovascular events both alone and in combination. STUDY DESIGN: All female patients discharged from French hospitals in 2013 with 5 years of subsequent and complete follow-up were identified. They were grouped depending on their history of GDM, history of GH, history of both or history of neither. After propensity score matching, patients with GDM and/or GH were matched 1:1 with patients with no GDM or GH. Hazard ratios (HR) for cardiovascular events during follow-up were adjusted by age at baseline. RESULTS: Women with a history of GH had an increased risk of cardiovascular death (HR 5.46, 95 % confidence interval [CI] 1.93-15.49). Women with a history of GDM had no significant difference in the risk of cardiovascular events such as myocardial infarction (HR 0.88, 95 %CI 0.38-2.03) and cardiovascular death (HR 1.25, 95 %CI 0.47-3.36) during the 5 year follow up. Those with a history of both GDM and GH had a significantly increased risk of myocardial infarction (HR 23.33, 95 %CI 4.84-112.39). CONCLUSION: Women with a history of both GH and GDM are at a 23-fold increased risk of myocardial infarction within the first 5 years of their postnatal lives.

Gestational Diabetes Mellitus-Induced Milk Fat Globule Membrane Protein Changes of Human Mature Milk Based on TMT Proteomic Analysis.

Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breastmilk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with GDM and without based on tandem mass tag (TMT) labeling and liquid chromatography tandem mass spectrometry (LC-MS) techniques. A total of 5402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis (GSEA) involving all genes.

Effect of treatment for early gestational diabetes mellitus on neonatal respiratory distress: A secondary analysis of the TOBOGM study.

OBJECTIVE: To identify factors associated with neonatal respiratory distress (NRD) in early Gestational diabetes mellitus (eGDM). DESIGN: Nested case-control analysis of the TOBOGM trial. SETTING: Seventeen hospitals: Australia, Sweden, Austria and India. POPULATION: Pregnant women, <20 weeks' gestation, singleton, GDM risk factors. METHODS: Women with GDM risk factors completed an oral glucose tolerance test (OGTT) before 20 weeks: those with eGDM (WHO-2013 criteria) were randomised to immediate or deferred GDM treatment. Logistic regression compared pregnancies with/without NRD, and in pregnancies with NRD, those with/without high-dependency nursery admission for ≤24 h with those admitted for >24 h. Comparisons were adjusted for age, pre-pregnancy body mass index, ethnicity, smoking, primigravity, education and site. Adjusted odds ratios (95% CI) are reported. MAIN OUTCOME MEASURES: NRD definition: ≥4 h of respiratory support (supplemental oxygen or supported ventilation) postpartum. Respiratory distress syndrome (RDS): Supported ventilation and ≥24 h nursery stay. RESULTS: Ninety-nine (12.5%) of 793 infants had NRD; incidence halved (0.50, 0.31-0.79) if GDM treatment was started early. NRD was associated with Caesarean section (2.31, 1.42-3.76), large for gestational age (LGA) (1.83, 1.09-3.08) and shorter gestation (0.95, 0.93-0.97 per day longer). Among NRD infants, >24 h nursery-stay was associated with higher OGTT 1-h glucose (1.38, 1.08-1.76 per mmol/L). Fifteen (2.0%) infants had RDS. CONCLUSIONS: Identifying and treating eGDM reduces NRD risk. NRD is more likely with Caesarean section, LGA and shorter gestation. Further studies are needed to understand the mechanisms behind this eGDM complication and any long-term effects.

Untargeted metabolomics study of mature human milk from women with and without gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy that alters the metabolites in human milk. Integrated Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were employed for comprehensive identification and comparison of metabolites in mature human milk (MHM) from women with and without GDM. A total of 268 differentially expressed metabolites (DEMs) were identified. Among these, linoleic acid, arachidonic acid, 9R-HODE and L-glutamic acid were significantly elevated and 12,13-DHOME was significantly decreased in MHM of women with GDM. These metabolites are significantly enriched in linoleic acid metabolism, fatty acid biosynthesis, galactose metabolism and ABC transporters pathways. Disorders in these metabolic pathways are associated with insulin resistance and poor glucose metabolism indicating these conditions may persist postpartum.

The effect of gestational diabetes mellitus on postnatal mother-infant bonding: Findings from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is associated with considerable psychological burden for women. In qualitative research, women with GDM describe increased awareness about their bonding with their infant, potentially resulting from the highly medicalised nature of the condition. The primary aim is to examine quantitatively whether GDM was associated with lower mother-infant bonding in the postnatal period. METHODS: Data were analysed from 10,419 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017 in Japan. GDM status was collected from hospital records and measured using the oral glucose tolerance test. Mother-infant bonding was assessed using the Japanese version of Mother-to-Infant Bonding Scale (MIBS-J) at one-month postpartum, higher scores representing lower bonding. Data were analysed in SAS using multiple regression adjusting for relevant confounders. RESULTS: GDM did not appear to be associated with worse mother-infant bonding scores at one-month postpartum. There was a non-significant unadjusted trend in the mean mother-infant bonding scores and the proportion with bonding disorder (n = 4 (4.12%) versus n = 969 (9.39%)) in the GDM versus non GDM group respectively, indicating higher self-reported bonding in the GDM group, and this remained not statistically significant in the adjusted analyses. CONCLUSIONS: We observed the reverse of our hypothesis, that there was a trend for women with GDM to self-report higher bonding compared to non-GDM women. There is need to replicate this finding in cohorts specifically designed to measure GDM-specific psychological distress.

Barriers and system improvements for physical activity promotion after gestational diabetes: A qualitative exploration of the views of healthcare professionals.

AIM: Physical activity is an important behaviour for managing the ten times increased risk of type 2 diabetes after gestational diabetes. Previous studies exploring physical activity promotion in healthcare focus on general practitioners but have not explored the gestational diabetes pathway. Therefore, this paper explores the barriers to and suggestions for, activity promotion along the gestational diabetes healthcare pathway. METHODS: The paper was written in accordance with the Standards for Reporting Qualitative Research. Patient and Public Involvement with women who had lived experiences of gestational diabetes informed purposeful sampling by identifying which healthcare professional roles should be targeted in participant recruitment. Participants were recruited through word-of-mouth, that is, email and connections with local healthcare service leads. Twelve participants took part in semi-structured one-to-one interviews, analysed using reflexive thematic analysis. RESULTS: Participants included a Public Health Midwife (n = 1), Diabetes Midwifes (n = 3), Diabetes Dietitian (n = 1), Diabetes Consultants (n = 2), Diabetes Specialist Nurse (n = 1), general practitioners (n = 2), Practice nurse (n = 1) and a Dietitian from the UK National Diabetes Prevention Program (n = 1). Six themes were generated: 'management of gestational diabetes takes precedent', 'poor continuity of care', 'lack of capacity to promote PA', 'beliefs about the acceptability of PA promotion', 'resources to support conversations about PA' and 'adapting healthcare services for women post-gestational diabetes'. CONCLUSIONS: During pregnancy messaging around physical activity is consistent, yet this is specific for managing gestational diabetes and is not followed through postnatally. Improvements in continuity of care are necessary, in addition to ensuring the availability and links with wider exercise and activity schemes.

Gut antibiotic resistome during pregnancy associates with the risk of gestational diabetes mellitus: New evidence from a prospective nested case-control study.

Antibiotic resistome has emerged as a global threat to public health. However, gestational antibiotic resistome and potential link with adverse pregnancy outcomes remains poorly understood. Our study reports for the first time an association between gut antibiotic resistome during early pregnancy and the risk of gestational diabetes mellitus (GDM) based on a prospective nested case-control cohort including 120 cases and 120 matched controls. A total of 214 antibiotic resistance gene (ARG) subtypes belonging to 17 ARG types were identified in > 10 % fecal samples collected during each trimester. The data revealed dynamic profiles of gut antibiotic resistome through pregnancy, and significant positive associations between selected features (i.e., ARG abundances and a GDM-ARG score which is a new feature characterizing the association between ARGs and GDM) of gut antibiotic resistome during early pregnancy and GDM risk as well as selected endogenous metabolites. The findings demonstrate ubiquitous presence of ARGs in pregnant women and suggest it could constitute an important risk factor for the development of GDM.

Landscapes of maternal and neonatal gut microbiome and plasma metabolome signatures and their interaction in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and foetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the foetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures. METHODS: This study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycaemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyse the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics. RESULTS: Distinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycaemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between Qipengyuania and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycaemic mothers and newborns, but these correlations were disrupted in the GDM group. CONCLUSION: Our findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.

Immunometabolic profiling related with gestational diabetes mellitus: a nested case-control study of CD4+ T cell phenotypes and glycemic traits.

AIMS: To investigate immunometabolic associations of CD4+ T cell phenotypes with gestational diabetes mellitus (GDM). METHODS: A nested case-control study was conducted comprising 53 pairs of GDM patients and matched controls within a prospective cohort. Metabolomic signatures related to both CD4+ T cell phenotypes and glycemic traits among pregnant women were investigated by weighted gene co-expression network analysis (WGCNA). Multivariable-adjusted generalized linear models were used to explore the associations of CD4+ T cell phenotypes and selected metabolites with GDM. Mediation analysis was conducted to evaluate the mediating effect of selected metabolites on the relationship between CD4+ T cell phenotypes and glycemic traits. RESULTS: Higher levels of Treg cells (OR per SD increment (95%CI): 0.57 (0.34, 0.95), p = 0.031) and increased expression of Foxp3 (OR per SD increment (95%CI): 0.59 (0.35, 0.97), p = 0.039) and GATA3 (OR per SD increment (95%CI): 0.42 (0.25, 0.72), p = 0.002) were correlated with a decreased risk of GDM. Plasma pyruvaldehyde, S-adenosylhomocysteine (SAH), bergapten, and 9-fluorenone mediated the association between Tregs and fasting plasma glucose (FPG), with mediation proportions of 46.9%, 39.6%, 52.4%, and 56.9%, respectively. CONCLUSIONS: Treg cells and Foxp3 expressions were inversely associated with GDM risk, with potential metabolic mechanisms involving metabolites such as pyruvaldehyde and SAH.