Venous thromboembolism (VTE) is a leading cause of maternal mortality, yet effective biomarkers for early prediction of adverse pregnancy outcomes remain limited. We aimed to investigate the association between changes in thrombin-antithrombin complex (TAT) levels and adverse pregnancy outcomes in early-pregnancy patients with VTE.

In this retrospective cohort study, we enrolled 89 pregnant women diagnosed with VTE during early pregnancy (< 14 weeks) who received care at Fujian Maternity and Child Health Hospital between June 2021 and May 2024. Plasma TAT levels measured in early and mid-pregnancy were collected as exposure variables, while adverse pregnancy outcomes (including miscarriage, preterm birth, and fetal growth restriction) served as outcome variables. Multivariate regression analysis was performed to evaluate the association between TAT level changes and adverse pregnancy outcomes, adjusting for potential confounding factors including age, BMI, and obstetric history. Additionally, threshold effect analysis was conducted.

After adjusting for potential confounding factors including age, BMI, and underlying conditions, changes in TAT levels were significantly associated with a reduced risk of adverse pregnancy outcomes (adjusted OR = 0.62, 95% CI: 0.47-0.80). Threshold effect analysis identified a critical turning point of -2.87 in TAT level changes (TATp2-1), below which the risk of adverse outcomes increased significantly (adjusted OR = 0.37, 95% CI: 0.22-0.63).

The association between TATp2-1 and adverse pregnancy outcomes in early pregnancy VTE patients was non-linear. A threshold effect was observed with an inflection point of -2.87. When the TATp2-1 were below - 2.87, there was a significantly increased risk of adverse pregnancy outcomes.

Gestational Diabetes Mellitus (GDM) is a hyperglycaemic condition diagnosed during pregnancy. GDM is strongly associated with future development of type 2 diabetes and cardiovascular disease. Lifestyle and pharmacological interventions can reduce the risk of developing type 2 diabetes. General practice is the recommended setting for long-term follow-up of women with a history of GDM. However, rates of follow-up are suboptimal. The evidence around long-term general practice healthcare for women with a history of GDM has not previously been reviewed.

The aim of this scoping review is to explore the current evidence base for the long-term care of women with a history of GDM in general practice.

The study described by this protocol is a scoping review. The study design was informed by Joanna Briggs Institute methodology.

Empirical qualitative and quantitative research studies published since 2014 will be identified from a search of the following databases: MEDLINE (Ovid), EMBASE (Elsevier), CINAHL, PsycINFO, Academic Search Complete and SocIndex. The review will identify key characteristics of the literature. Framework analysis will be used to map the findings against the Chronic Care Model, a primary care-based framework that sets out the core components for optimal long-term healthcare.

A numerical descriptive summary (using frequencies) will describe the overall extent of literature, and the range and distribution of its component parts, including the geographical and economic settings, research methods, interventions, outcomes and findings. The qualitative analysis will map interventions and descriptions of care to components of the chronic care model. Research gaps will be reported, and research needs and priorities will be suggested.

The findings of this scoping review will have the potential to inform future research efforts in the area.

This protocol has been registered in Open Science Framework ( https://osf.io/bz2vh).

Early pregnancy folate has been associated with GDM and possible adiposity in the newborn. The present study examined associations between maternal early pregnancy folate levels and sex-specific neonatal anthropometry. We further explored possible mediation by maternal glycemia on the association between folate and neonatal adiposity.

Sub-group data (n = 511) from a UK multi-ethnic early pregnancy longitudinal study (micronutrients in Pregnancy as a Risk factor for gestational Diabetes and Effects on mother and baby; PRiDE) was used. Maternal serum folate was assessed during early pregnancy (Mean ± SD = 12.5 ± 1.6 gestational weeks) and infant anthropometry including skinfold thickness (SFT) and mid-upper arm circumference (MUAC) at birth. Multiple linear regression was performed to analyse the relationship between maternal folate and infant adiposity indices. Interaction analysis was used to identify maternal glucose mediation of this relationship.

Excess folate levels (≥45 nmol/l) were found in 40.3 % pregnant women (n = 206). Early pregnancy folate (1 SD unit) was positively associated with male newborn triceps SFT (std β = 0.17 (95 % CI: 0.06, 0.29; p < 0.05)) after adjusting for key maternal and infant confounders in multiple comparisons using Benjamini-Hochberg procedure. However, no associations were seen in female newborns. No influence of maternal fasting (FPG) and 2-h plasma glucose (2 h-PG) were detected on the association between folate and newborn anthropometry.

Our findings suggest a potential sex-specific influence of maternal folate on infant anthropometric indices. The association between early pregnancy folate on newborn adiposity was not mediated by maternal FPG and/or 2 h-PG at 24-28 weeks.

Background: Breastfeeding is widely regarded as the optimal method of infant nutrition. A notable benefit of breastfeeding is its potential to avert the development of childhood overweight and obesity. This assertion holds particular significance in the context of infants whose mothers have exhibited gestational diabetes, a condition that has been demonstrated to be associated with an increased risk of carbohydrate and/or fat disorders in offspring, potentially leading to the onset of overweight and obesity in later life. Objective: The objective of the present study was to examine the variations in the anthropometric dimensions of infants across three distinct time points during the initial year of life, with a particular focus on the correlation between infant feeding practices and the prevalence of gestational diabetes in maternal subjects. Additionally, this study encompassed an analysis of the disparities in anthropometric dimensions between infant males and females. Methods: The study population included 42 infants whose mothers had been diagnosed with gestational diabetes between the 24th and 28th week of pregnancy, as well as 28 infants of women without gestational diabetes. The infants' dietary habits, including breastfeeding, mixed feeding, and formula feeding, were assessed, and their anthropometric measurements were obtained at three time points: 7 ± 1 weeks postpartum, 6 months ± 1 week postpartum, and 12 months ± 1 week postpartum. The infants were measured for weight, length, head circumference, and thickness of the subscapular skin fold. We also calculated their BMI and Ponderal Index, and the measurements were referenced to WHO centile grids. Results: At 7 ± 1 weeks postpartum, exclusively breastfed infants exhibited higher weight compared to those who were mixed-fed or formula-fed (p = 0.03). However, at 1 year of age, breastfed infants demonstrated significantly lower weight compared to formula-fed infants (p = 0.019). Furthermore, at 12 months, breastfed boys exhibited lower weight, length, BMI, and lower subscapular skinfold thickness compared to formula-fed infants. Conclusions: Breastfeeding has been shown to play a pivotal role in preventing obesity in children. In the initial postnatal period, infants who are fed breast milk exhibit a higher weight compared to those who are fed formula. However, by the age of 12 months, the weight of breastfed infants typically falls below that of formula-fed infants. Diabetes during pregnancy has been observed to have no impact on the anthropometric dimensions of infants up to the age of one. Nevertheless, further research is necessary to comprehensively assess the long-term implications of maternal GDM in their offspring.

Initiated in 2010, the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort investigates the pathophysiology of impaired glycaemic regulation in pregnancy and evaluates its impact on both the mothers and her offspring health trajectory. Follow-up visits 3 and 5 years after delivery aimed to investigate pregnancy-related risk factors such as maternal obesity and gestational hyperglycaemia in relation to the mother's metabolic health after pregnancy, and with offspring health outcomes such as risk of obesity and neurodevelopmental problems in early childhood. We also investigated molecular mechanisms involved in the fetal programming of these later health outcomes.

Of the 1024 women originally recruited in the first trimester of pregnancy, we have targeted the 854 who had complete glucose tolerance test data and the 724 newborns who provided placenta and/or cord blood samples for follow-up recruitment. Of these, 695 mother-child dyads agreed to be contacted for the prospective follow-up visits. 448 and 521 mother-child dyads completed the research visits at 3 and 5 years after delivery respectively.

At both visits, we collected the mother's and child's medical history, lifestyle (using validated questionnaires), sociodemographic status, anthropometric measurements, mother's blood samples, child's saliva samples and growth charts. At the 5-year-old visit, we additionally collected the mother's and child's urine and stool samples and the child's blood samples; we performed a 75 g oral glucose tolerance test in the mothers and assessed the body composition in children using dual-energy X-ray absorptiometry. Using the Gen3G rich longitudinal data set, we have enhanced the understanding of the pathophysiology and characterisation of the heterogeneity of gestational diabetes mellitus, and we have shown that gestational hyperglycaemia and insulin resistance are associated with offspring epigenetics (DNA methylation) variations in the placenta, cord blood and blood at 5 years of age, as well as with offspring anthropometric, metabolic and neurodevelopmental outcomes in early childhood.

We are currently conducting a prospective follow-up of mothers and their children 12 years after delivery to study how prenatal and early-life metabolic factors may programme childhood adiposity and obesogenic dietary behaviours. This follow-up should be completed by the end of 2026.

This study provides a comprehensive examination of gestational diabetes mellitus (GDM), shedding light on the geographical and ethnic variations in its prevalence. It elucidates the diagnostic evolution, noting the transition from rudimentary glucose tests to the more sophisticated Oral Glucose Tolerance Test (OGTT), which not only facilitates early detection but also standardizes screening protocols. The study delves into the evolution of GDM diagnosis, emphasizing the standardization of the OGTT and its pivotal role in enhancing early detection rates. It meticulously discusses holistic management approaches for GDM, encompassing tailored dietary interventions, prescribed physical activity, and pharmacotherapy. The need for individualized strategies to optimize glucose control is strongly emphasized. The study underscores the significance of mental health in GDM management, advocating for integrated psychological support and stress management interventions to bolster metabolic regulation. An exploration of telemedicine and artificial intelligence highlights their potential to revolutionize GDM care by enabling real-time monitoring and personalized interventions, thus improving patient outcomes. An analysis of health policies and educational efforts underscores their impact on GDM management, advocating for proactive measures to mitigate its prevalence through public health initiatives. The study identifies key research gaps and offers a focused analysis of critical advancements in GDM management, including personalized care strategies and the role of innovative technologies such as artificial intelligence and telemedicine in improving outcomes. Finally, the study calls for further research into personalized treatment modalities and innovative diagnostic tools to address existing gaps in GDM management, particularly in diverse demographic groups.

This study addresses a gap in research on predictive models for postpartum dyslipidemia in women with gestational diabetes mellitus (GDM). The goal was to develop a machine learning-based model to predict postpartum dyslipidemia using early pregnancy clinical data, and the model's robustness was evaluated through both internal and temporal validation. Clinical data from 15,946 pregnant women were utilized. After cleaning, the data were divided into two sets: Dataset A (n = 1,116), used for training and evaluating the model, and Dataset B (n = 707), used for temporal validation. Several machine learning algorithms were applied, and the performance of the model was assessed with Dataset A, while Dataset B was used to validate the model across a different time period. Feature significance was evaluated through Information Value (IV), model importance analysis, and SHAP (SHapley Additive exPlanations) analysis. The results showed that among the five machine learning algorithms tested, tree-based ensemble models, such as XGBoost, LightGBM, and Random Forest, outperformed others in predicting postpartum dyslipidemia. In Dataset A, these models achieved accuracies of 70.54%, 70.54%, and 69.64%, respectively, with AUC-ROC values of 73.10%, 71.94%, and 76.14%. Temporal validation with Dataset B indicated that XGBoost performed best, achieving an accuracy of 81.05% and an AUC-ROC of 87.92%. The predictive power of the model was strengthened by key variables such as total cholesterol, fasting glucose, triglycerides, and BMI, with total cholesterol being identified as the most important feature. Further IV and SHAP analyses confirmed the pivotal role of these variables in predicting dyslipidemia. The study concluded that the XGBoost-based predictive model for postpartum dyslipidemia in GDM showed strong and consistent performance in both internal and temporal validations. By introducing new variables, the model can identify high-risk groups during early pregnancy, supporting early intervention and potentially improving pregnancy outcomes and reducing complications.

Embedded in the developmental origins of health and disease (DOHaD) hypothesis, maternal hyperglycemia in utero, from preexisting diabetes or gestational diabetes mellitus, predisposes the offspring to excess adiposity and heightened risk of prediabetes and type 2 diabetes development. This transmission creates a vicious cycle increasing the presence of diabetes from one generation to another, leading to the question: How can we interrupt this vicious cycle? In this article, we present the current state of knowledge on the intergenerational transmission of diabetes from epidemiological life course studies. Then, we discuss the potential mechanisms implicated in the intergenerational transmission of diabetes with a focus on epigenetics. We present novel findings stemming from epigenome-wide association studies of offspring DNA methylation in blood and placental tissues, which shed light on potential molecular mechanisms implicated in the mother-offspring transmission of diabetes. Lastly, with a perspective on how to break the cycle, we consider interventions to prevent offspring obesity and diabetes development before puberty, as a critical period of the intergenerational cycle. This article is part of a series of perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program.

The placenta has a central function in fetal glucose supply and placental volume has received rising awareness as a potential predicting factor for adverse pregnancy outcomes. We aimed to examine whether placental volume is a prognostic marker for metabolic perturbations affecting both mother and child. Data from 100 women participating in a longitudinal cohort study of healthy pregnant women were obtained. Placental volume was assessed via transabdominal ultrasound at gestational weeks 12-14. Additional ultrasound measurements were conducted at gestational weeks 23-25, 28-30, and 34-36 to assess fetal anthropometry. HbA1c was measured in first trimester blood samples. Both cross-sectional and prospective associations between first trimester placental volume and selected fetal and maternal parameters were examined using multivariable linear regression models. Interactions by gender were observed for associations with HbA1c, anterior abdominal wall thickness (AAWT), gestational weight gain and estimated fetal weight. A higher first trimester placental volume was related to higher HbA1c levels in the first trimester, higher AAWT measures in the third trimester, and greater gestational weight gain in women carrying a male fetus only (all p = 0.02). In women carrying a female fetus, a positive association was observed between placental volume and estimated fetal weight at gestational week 34-36 (p = 0.045). None of the other maternal or fetal parameters were related to placental volume (p ≥ 0.1). Our results indicate first trimester placental volume to be a potential prognostic factor for maternal glucose metabolism and both fetal and maternal anthropometric perturbations particularly for those mothers carrying a male fetus.

This study aimed to identify and evaluate risk factors associated with gestational diabetes mellitus (GDM) in mainland China.

Eight electronic databases were searched for literature published from January 2010 until December 2023. Heterogeneity was quantified using I2. Data were pooled by fixed or random effects models and expressed as odds ratio and 95% confidence intervals.

A total of 69 observational studies with an overall sample size of 2,138,032 Chinese women and 219,303 patients with GDM were included in the analysis. After adjusting confounders, older maternal age (OR = 1.12, 95% CI: 1.09-1.15), maternal age ≥35 years (OR = 1.96, 95% CI: 1.74-2.21), higher pre-pregnancy body mass index (OR = 1.24, 95% CI: 1.17-1.32), pre-pregnancy overweight (OR = 1.78, 95% CI: 1.64-1.92) or obesity (OR 2.52, 95% CI: 2.06-3.08), family history of diabetes (OR = 1.85, 95% CI: 1.58-2.17), history of GDM (OR = 4.09, 95% CI: 2.13-7.82), and elevated levels of fasting plasma glucose (OR = 2.54, 95% CI: 2.13-3.01), hemoglobin (OR = 1.47, 95% CI: 1.14-1.89) and serum triglycerides (OR = 1.69, 95% CI: 1.31-2.16) in early pregnancy were associated with an increased risk of GDM in mainland China. But gravidity ≥2 (OR = 1.06, 95% CI: 0.89-1.27), conception by assisted reproductive technology analyses (OR = 1.54, 95% CI: 0.95-2.51) were not associated with GDM, and parity ≥1 (OR = 0.88, 95% CI: 0.82-0.94) was related to lower risk of GDM. In available unadjusted studies, history of abortion (OR = 1.34, 95% CI: 1.31-1.37) increased risk of GDM, non-Han ethnicity (OR = 0.78, 95% CI: 0.59-1.03) and high school or lower education level (OR1.09, 95% CI: 0.94-1.26) showed no correlation with GDM.

The key risk factors for GDM in mainland China included older maternal age, maternal age ≥35 years, pre-pregnancy overweight or obesity, family history of diabetes, history of GDM, elevated levels of FPG, Hb, and serum TG in early pregnancy. Early identification and intervention for women at high risk should be performed to prevent the development of GDM.

The prevalence of gestational diabetes mellitus (GDM) is rising and poses important health risks for the mother, developing fetus and offspring, even when maternal glycemic control is well managed. This study aimed to identify the differently expressed metabolites (DEMs) in maternal plasma between GDM pregnancies with good glycemic control and healthy pregnancies, along with the DEMs-related metabolism in adipose tissue. Pregnant women with scheduled caesarean sections were recruited. Venous blood samples were collected on the day prior to delivery for targeted metabolomics analysis focusing on the 200 polar metabolites in central carbon metabolism. Subcutaneous and omental white adipose tissue (sWAT and oWAT) were harvested at delivery. A total of 162 metabolites were quantified, revealing 2 up-regulated (D-glucose 6-phosphate (G6P), succinate) and 8 down-regulated DEMs, which exhibited a fold change of ≥ 1.5 or ≤ 0.67, respectively. Among the down-regulated DEMs, 5 metabolites-pyridoxine, glycine, S-methyl-L-cysteine, methionine, and S-carboxymethyl-L-cysteine-are related to one-carbon metabolism (OCM). In response to perturbation in circulating OCM, boosted methionine cycle, NAD + metabolism, and adipogenesis were observed in sWAT of GDM subjects, with no changes detected in oWAT. None of the 10 DEMs correlates with either blood glucose or insulin, but showed significant correlations with TG, TC, LDL-C and HDL-C. The present study indicates that sWAT compensates for the perturbations in circulating OCM associated with GDM and targeting to the OCM may be an effective strategy to control the long-term metabolic risk of GDM offsprings.

This study examined the association of gravida C-peptide with progeny islet function and insulin sensitivity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS).

Pregnancy 3rd trimester oral glucose tolerance test (OGTT), cord blood, and offspring OGTT glucose, C-peptide and insulin at age 10-14 years were analyzed for 4,121 mother-child dyads. Gravida fasting and 1-hour C-peptide concentration correlations with cord blood and childhood C-peptide, insulin, insulinogenic index and insulin sensitivity, and insulin resistance [HOMA-IR]), were assessed by multiple linear regression. Maternal covariates included age, gestational age, BMI and glucose at OGTT; child covariates included age, sex, pubertal stage, BMI z score and glucose.

Gravida fasting and 1-hour OGTT C-peptide was positively correlated with cord blood C-peptide, offspring OGTT C-peptide and insulin concentrations at fasting, 30 min, 1-hour and 2-hour at 10-14 years of age. Maternal fasting and 1-hour C-peptide concentrations were positively correlated with the insulinogenic index and HOMA-IR but inversely correlated with insulin sensitivity. Maternal C-peptide explained more variance than maternal glucose concentrations (3.0-17.9 % vs 0.2-3.5 %).

The correlation between gravida and offspring C-peptide suggests that without crossing the placenta, insulin may influence the offspring pancreatic beta-cell development and insulin sensitivity.

Gestational diabetes mellitus (GDM) affects over 10% of all pregnancies, both in Korea and worldwide. GDM not only increases the risk of adverse pregnancy outcomes such as preeclampsia, preterm birth, macrosomia, neonatal hypoglycemia, and shoulder dystocia, but it also significantly increases the risk of developing postpartum type 2 diabetes mellitus and cardiovascular disease in the mother. Additionally, GDM is linked to a higher risk of childhood obesity and diabetes in offspring, as well as neurodevelopmental disorders, including autistic spectrum disorder. This review offers a comprehensive summary of clinical epidemiological studies concerning maternal and fetal complications and explores mechanistic investigations that reveal the underlying pathophysiology.

Appropriate weight gain reduces the risk of fetal macrosomia and large for gestational age (LGA) in women with gestational diabetes mellitus (GDM), especially in the second and third trimester. This study aims to identify the optimal weight g-ain for such women across several pre-pregnancy body mass index (BMI) categories to lower the risk of macrosomia and LGA.

This retrospective cohort study enrolled women with GDM in north Taiwan who delivered between January 2012 and July 2022. BMI cut-offs were based on Chinese-specific guidelines and used to classify the participants as underweight (<18.5 kg/m2), normal weight (18.5-24.0 kg/m2), overweight (24.0-28.0 kg/m2), or obese (>28 kg/m2). Receiver operator curve analysis was used to determine the optimum GWG cut-off ranges to predict macrosomia / LGA, and uni- and multivariate analyses were used to analyze risk factors. In addition, a multivariable model predicting macrosomia and LGA in infants was developed.

A total of 963 participants was included in our analysis. Optimal mean weekly rates of GWG in the second and third trimesters were 0.43 kg/week and 0.61 kg/week, respectively, in the underweight and normal weight group, and 0.33 kg/week and 0.32 kg/week, respectively, in the overweight and obesity group.

The 2009 IOM guidelines, offering weight gain recommendations for pregnant women, appear to be applicable to Asian women diagnosed with GDM. This indicates that it is essential for such women to maintain an adequate total GWG throughout pregnancy. Physicians should address GWG using the IOM guidelines and trigger intervention when it is required to reduce macrosomia and LGA occurrence.

The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.

We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.

Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.38 to 1.96), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.

Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Gestational diabetes mellitus (GDM) has been associated with several fetal complications, such as macrosomia and fetal growth restriction (FGR). Infants from GDM associated FGR are at increased risk for adult-onset obesity and associated metabolic disorders. However, the underlying mechanisms of GDM associated FGR remain to be explored.

We analyzed placentas from GDM patients with FGR for ferroptosis markers and GLUT1 expression. High glucose conditions were established by adding different concentrations of D-Glucose to the 1640 cell culture medium. RSL3 were used to test ferroptosis sensitivity in trophoblast cells. GLUT1 was inhibited using siRNA or its inhibitor WZB117 to assess its impact on ferroptosis inhibition in HTR8/SVneo cell line. Mechanistic studies explored the effects of GLUT1 on AMPK and ACC phosphorylation, which in turn impacted lipid metabolism and ferroptosis. In mouse models, streptozotocin (STZ)-induced GDM was treated with WZB117 and the ferroptosis inhibitor liproxstatin-1 (Lip-1). Finally, AMPK and ACC phosphorylation levels were evaluated in GDM patient samples.

In this study, placentas from GDM patients with FGR showed signs of ferroptosis and upregulation of GLUT1. In cell models, high glucose conditions sensitized trophoblast cells to ferroptosis and induced GLUT1 expression. Interestingly, GLUT1 inhibition significantly suppressed ferroptosis in trophoblast cells under high glucose conditions. Mechanistically, elevated GLUT1 inhibited AMPK phosphorylation and reduced ACC phosphorylation, thereby promoting lipid synthesis and facilitating ferroptosis. In pregnant mice, STZ-induced hyperglycemia led to FGR, and treatment with either the GLUT1 inhibitor WZB117 or the ferroptosis inhibitor Lip-1 alleviated the FGR phenotype. Moreover, in vivo elevation of GLUT1 increased ferroptosis markers, decreased AMPK/ACC phosphorylation, and resulted in altered lipid metabolism, which likely contributed to the observed phenotype. Finally, placental samples from GDM patients showed reduced AMPK and ACC phosphorylation.

Our findings suggest a potential role of ferroptosis in GDM associated FGR and indicate that the dysregulated GLUT1-AMPK-ACC axis may be involved in the pathogenesis of GDM associated FGR in clinicals.

Air pollution is detrimental to pregnancy adversely affecting maternal and child health. Our objective was to unravel epigenetic mechanisms mediating the effect of preconception, periconception, and gestational exposure to inhaled air pollutants (AP) upon the maternal and placental-fetal phenotype and explore the benefit of an omega-3 rich dietary intervention. To this end, we investigated intranasal instilled AP during 8 weeks of preconception, periconception, and gestation (G; D0 to 18) upon GD16-19 maternal mouse metabolic status, placental nutrient transporters, placental-fetal size, and placental morphology. Prepregnant mice were glucose intolerant and insulin resistant, while pregnant mice were glucose intolerant but displayed no major placental macro-nutrient transporter changes, except for an increase in CD36. Placentas revealed inflammatory cellular infiltration with cellular edema, necrosis, hemorrhage, and an increase in fetal body weight. Upon examination of placental genome-wide epigenetic processes of DNA sequence specific 5'-hydroxymethylation (5'-hmC) and 5'-methylation (5'-mC) upon RNA sequenced gene expression profiles, revealed changes in key metabolic, inflammatory, transcriptional, and cellular processing genes and pathways. An omega-3 rich anti-inflammatory diet from preconception (8 weeks) through periconception and gestation (GD0-18), ameliorated all these maternal and placental-fetal adverse effects. We conclude that preconceptional, periconceptional and gestational exposures to AP incite a maternal inflammatory response resulting in features of pre-existing maternal diabetes mellitus with injury to the placental-fetal unit. DNA 5'-mC more than 5'-hmC mediated AP induced maternal inflammatory and metabolic dysregulation which together alter placental gene expression and phenotype. A dietary intervention partially reversing these adversities provides possibilities for a novel nutrigenomic therapeutic strategy.

The objective of this study was to assess maternal gestational outcomes and offspring growth trajectories following prepregnancy metabolic and bariatric surgery (MBS) compared with non-MBS controls.

Single-center deliveries between January 2020 and March 2023 with prepregnancy Roux-en-Y gastric bypass (herein referred to as "bypass"), sleeve gastrectomy (herein referred to as "sleeve"), and non-MBS controls were included. Offspring growth trajectories were compared with the World Health Organization child growth standards. Linear mixed models assessed MBS-bypass and MBS-sleeve offspring weight, length, and BMI trajectories with a prepregnancy BMI 27 to 37 kg/m2 and propensity score-matched controls.

The study included 440 participants with prepregnancy MBS (MBS-bypass, 185; MBS-sleeve, 225; 76% Hispanic/Latino) and 13,434 non-MBS controls. Gestational weight gain and gestational diabetes mellitus were similar, whereas hypertensive disorders of pregnancy were more common after MBS. The post-MBS offspring had lower birth weight but higher weight gain at 24 months (sleeve, +1.4 kg [95% CI: 1.0-1.9]; bypass, +0.5-0.7 kg [95% CI: 0.0-1.2]) compared with non-MBS groups. Male children had higher weight gain than females. The post-MBS-sleeve but not the post-MBS-bypass offspring had higher BMI z scores.

The higher early-life weight gain and sex differences in the post-MBS-sleeve group compared with the post-MBS-bypass group provide a window toward elucidating pathways to mitigate intergenerational metabolic risk transfer.

Studies have shown that plant-based foods have a protective effect against gestational diabetes (GDM). We examined the association between plant-based dietary patterns and the risk of GDM in a sample of Iranian adults.

We enrolled 635 pregnant women for the present study. Dietary intakes were evaluated by using a 90-item food frequency questionnaire during the first trimester of pregnancy. Three plant-based including plant-based (PDI), unhealthy (uPDI) and healthy (hPDI) were calculated. Cox proportional hazard model were fitted to estimate hazard ratio (HR) and 95% confidence interval (CI) of GDM across categories of the plan-based dietary indices, while controlling for age, educational level, physical activity, family income, prepregnancy body mass index, gestational weight gain, and total energy intake.

A total of 635 mothers were included, of whom 79 participants were diagnosed with GDM. Those in the third tertile of the PDI (HR: 0.55, 95% CI: 0.30, 0.98) and hPDI (HR: 0.43, 95% CI: 0.24, 0.78) had a lower risk of developing GDM during their current pregnancy as compared to the first tertile. There was no association between uPDI and risk of GDM.

We found that higher adherence to a plant-based diet during early pregnancy may be associated with a lower GDM risk among Iranian women. Confirmation of this finding is necessary in larger cohort studies, taking into account other pregnancy outcomes such as birth weight.

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use.

In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org.

The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings.

NCT06445946.

Gestational diabetes mellitus (GDM) is the most prevalent metabolic disturbance during pregnancy and is associated with adverse outcomes in offspring, including an elevated risk for developing atopic diseases in early childhood. Research is limited regarding only women at risk of GDM among whom some develop GDM while others do not. Information about adverse health outcomes in the offspring of these women is also lacking. The main aim was to assess whether maternal GDM increases the offspring's risk of atopic dermatitis (AD), asthma and allergic rhinitis at 1, 2 and 5 years of age. The second aim was to analyze the association of other maternal health characteristics on the development of these disorders in offspring.

The follow-up study group of the Gestational Diabetes Study (GDS), conducted at Tartu University Hospital, Estonia, between 2014 and 2020, comprised 223 mother-child dyads. All women had at least one risk factor for GDM, of whom only some developed GDM. Information about the diagnoses of interest was obtained from Electronic Health Records. Allergen-specific IgE from children's serum was measured using ImmunoCAP™ Phadiatop™ Infant, with results ≥ 0.35 kU/l considered positive. Statistical analysis was performed using the RStudio software (version 4.3.0).

According to our results, only the cases of GDM requiring the use of antidiabetic medications were associated with the development of asthma and/or allergic rhinitis at 2 years of age (aOR 4.68, 95%CI 1.08-20.21, p = 0.039). Maternal obesity (BMI > 30) was associated with offspring´s asthma and/or allergic rhinitis diagnosis at 2 years of age (aOR 3.15, 95%CI 1.03-9.63, p = 0.045). Maternal abnormal weight gain during pregnancy was associated with asthma and/or allergic rhinitis at 5 years of age (aOR 2.76, 95%CI 1.04-7.31, p = 0.041).

Among pregnant women at risk for GDM, maternal weight-related factors significantly influence the development of atopic diseases in their children between 1 and 5 years of age, regardless of the GDM diagnosis. This suggests that, besides women with GDM greater attention should also be paid to women at risk but who do not develop GDM, as their children seem to be at higher risk of atopic diseases.

With the global prevalence of diabetes increasing, more people of reproductive age are experiencing hyperglycaemic pregnancies. Maternal Type 1 (T1DM) or Type 2 (T2DM) diabetes mellitus, and gestational diabetes mellitus (GDM) are associated with maternal cardiovascular and metabolic complications. Pregnancies complicated by maternal diabetes also increase the risk of short- and long-term health complications for the offspring, including altered fetal growth and the onset of T2DM and cardiometabolic diseases throughout life. Despite advanced methods for improving maternal glucose control, the prevalence of adverse maternal and offspring outcomes associated with maternal diabetes remains high. The placenta is a key organ at the maternal-fetal interface that regulates fetal growth and development. In pregnancies complicated by maternal diabetes, altered placental development and function has been linked to adverse outcomes in both mother and fetus. Emerging evidence suggests that microRNAs (miRNAs) are key molecules involved in mediating these changes. In this review, we describe the role of miRNAs in normal pregnancy and discuss how miRNA dysregulation in the placenta and maternal circulation is associated with suboptimal placental development and pregnancy outcomes in individuals with maternal diabetes. We also discuss evidence demonstrating that miRNA dysregulation may affect the long-term health of mothers and their offspring. As such, miRNAs are potential candidates as biomarkers and therapeutic targets in diabetic pregnancies at risk of adverse outcomes.

Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28-45 kg/m2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM.

Air pollution (AP) is detrimental to pregnancies including increasing risk factors of gestational diabetes mellitus. We hypothesized that exposure to AP causes cardiovascular and metabolic disruption thereby altering placental gene expression, which in turn affects the placental phenotype and thereby embryonic/fetal development. To test this hypothesis, we investigated the impact of intra-nasal instilled AP upon gestational day 16-19 maternal mouse cardiovascular and metabolic status, placental nutrient transporters, and placental-fetal size and morphology. To further unravel mechanisms, we also examined placental total DNA 5'-hydroxymethylation and bulk RNA sequenced gene expression profiles. AP exposed pregnant mice and fetuses were tachycardic with a reduction in maternal left ventricular fractional shortening and increased uterine artery with decreased umbilical artery systolic peak velocities. In addition, they were hyperglycemic, glucose intolerant and insulin resistant, with changes in placental glucose (Glut3) and fatty acid (Fatp1 & Cd36) transporters, and a spatial disruption of cells expressing Glut10 that imports L-dehydroascorbic acid in protecting against oxidative stress. Placentas revealed inflammatory cellular infiltration with associated cellular edema and necrosis, with dilated vascular spaces and hemorrhage. Placental and fetal body weights decreased in mid-gestation with a reduction in brain cortical thickness emerging in late gestation. Placental total DNA 5'-hydroxymethylation was 2.5-fold higher, with perturbed gene expression profiles involving key metabolic, inflammatory, transcriptional, cellular polarizing and processing genes and pathways. We conclude that gestational exposure to AP incites a maternal inflammatory response resulting in features mimicking maternal gestational diabetes mellitus with altered placental DNA 5'-hydroxymethylation, gene expression, and associated injury.

Obesity is an epidemic worldwide. Overweight and multiple obesity-related mechanisms, including dysmetabolic alterations, contribute to cardiovascular deleterious effects. Hence, overweight and obesity have been independently associated with increased cardiovascular risk, whose assessment is crucial for preserving life quality and reducing mortality, and to address appropriate therapeutic strategies in obese patients. Beyond the standard of care in managing overweight and obesity in adults (i.e., diet and physical exercise), several relevant pharmacotherapies have been approved, and several procedures and device types for weight loss have been recommended. In such a contest, medical weight management remains one option for treating excess weight. Most drugs used for obesity reduce appetite and increase satiety and, secondarily, slow gastric emptying to reduce body weight and, therefore, act also to improve metabolic parameters. In this contest, agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) modulate different metabolic pathways associated with glucose metabolism, energy homeostasis, antioxidation, and inflammation. Moreover, this class of drugs has shown efficacy in improving glycemic control, reducing the incidence of cardiovascular events in type 2 diabetic patients, and reducing body weight independently of the presence of diabetes. Recently, in overweight or obese patients with pre-existing cardiovascular disease but without diabetes, the GLP-1RA semaglutide reduced the incidence of cardiovascular and cerebrovascular events and death from cardiovascular causes. Thus, semaglutide has been approved for secondary prevention in obese people with cardiovascular disease. Nevertheless, whether this class of drugs is equally effective for primary prevention in obese people has to be demonstrated. In this review, we will summarize updates on the pathophysiology of obesity, the effects of obesity on cardiovascular risk, the impact of different obesity phenotypes on cardiovascular diseases, and the novelties in the clinical management of obesity for cardiovascular prevention.

Childhood obesity presents a significant public health concern globally, with implications for cardiovascular health and metabolic syndrome. In Portugal, approximately 31.6% of children are affected, highlighting the urgency for intervention strategies. This study aimed to assess the prevalence of overweight and obesity in Portuguese school-aged children, with a focus on sex and age differences.

Anthropometric measurements were conducted on 1564 children aged 6-10 years, including weight, height, and skinfold thickness. Body Mass Index (BMI) and the percentage of body fat were calculated using established methods.

The results revealed significant differences in BMI (≤0.001) and body fat percentage (≤0.001) among different BMI categories, with a notable prevalence of overweight and obesity, particularly among boys. A total of 37% of the studied population is overweight or obese, among which 40.1% and 33.9% are boys and girls, respectively.

This study highlights statistically significant differences in BMI and body fat percentage for both sexes in different BMI categories. A large proportion of the population is overweight or obese, with a greater prevalence in boys. In short, childhood obesity has a negative impact on body composition and is associated with significant differences in anthropometric parameters, emphasizing the importance of preventative and intervention strategies to address this health problem.

Gestational Diabetes Mellitus (GDM) poses significant risks to maternal and fetal health. Current diagnostic methods based on glucose tolerance tests have limitations for early detection. tRNA-derived small RNAs (tsRNAs) have emerged as potential molecular regulators in various diseases, including metabolic disorders. However, the diagnostic value of tsRNAs in plasma for early GDM or postpartum remains unclear.

This longitudinal study profiled the expression of tsRNAs across different gestational stages and postpartum in women with GDM (n = 40) and healthy control gestational women (HCs, n = 40). High-throughput small RNA sequencing identified candidate tsRNAs, which were then validated and correlated with clinical biochemical markers such as fasting blood glucose (FBG), HOMA-IR, and GHbA1c.

tRF-1:32-Val-AAC-1-M6, tRF-1:31-Glu-CTC-1-M2, and tRF-1:30-Gly-CCC-1-M4 were consistently upregulated in the GDM group compared to HCs during the second trimester (p < 0.05). Only tRF-1:31-Glu-CTC-1-M2 was highly expressed during the first trimester, and tRF-1:30-Gly-CCC-1-M4 increased during postpartum. tRF-1:31-Glu-CTC-1-M2 showed a significant correlation with FBG levels in the first trimester (R = 0.317, p = 0.047). The expression of tRF-1:30-Gly-CCC-1-M4 was significantly correlated with HOMA-IR (r = 0.65, p < 0.001) and GHBA1c (r = 0.33, p = 0.037) during postpartum. A joint diagnostic model incorporating tsRNAs expression and clinical markers demonstrated enhanced predictive power for GDM (ROC AUC = 0.768).

Our results revealed distinct expression patterns of specific tsRNAs in GDM, showcasing their correlation with key metabolic parameters. This underscores their promising role as biomarkers for early prediction and diagnosis of GDM. The integration of tRFs into a composite biomarker panel holds the potential to improve clinical outcomes by enabling personalized risk assessment and targeted interventions.

Gestational diabetes mellitus (GDM) is associated with cardiovascular disease in postnatal life. The current study tested the hypothesis that GDM caused the cardiac hypertrophy in fetal (ED18.5), postnatal day 7 (PD7), postnatal day 21 (PD21) and postnatal day 90 (PD90) offspring by upregulation of BRD4 and mitochondrial dysfunction. Pregnant mice were divided into control and GDM groups. Hearts were isolated from ED18.5, PD7, PD21 and PD90. GDM increased the body weight (BW) and heart weight (HW) in ED18.5 and PD7, but not PD21 and PD90 offspring. However, HW/BW ratio was increased in all ages of GDM offspring compared to control group. Electron microscopy showed disorganized myofibrils, mitochondrial swelling, vacuolization, and cristae disorder in GDM offspring. GDM resulted in myocardial hypertrophy in offspring, which persisted from fetus to adult in a sex-independent manner. Echocardiography analysis revealed that GDM caused diastolic dysfunction, but had no effect on systolic function. Meanwhile, myocardial BRD4 was significantly upregulated in GDM offspring and BRD4 inhibition by JQ1 alleviated GDM-induced myocardial hypertrophy in offspring. Co-immunoprecipitation showed that BRD4 interacted with DRP1 and there was an increase of BRD4 and DRP1 interaction in GDM offspring. Furthermore, GDM caused the accumulation of damaged mitochondria in hearts from all ages of offspring, including mitochondrial fusion fission imbalance (upregulation of DRP1, and downregulation of MFN1, MFN2 and OPA1) and myocardial mitochondrial ROS accumulation, which was reversed by JQ1. These results suggested that the upregulation of BRD4 is involved in GDM-induced myocardial hypertrophy in the offspring through promoting mitochondrial damage in a gender-independent manner.

Gestational diabetes is the most common medical complication in pregnancy. Historically, gestational diabetes was considered a pregnancy complication involving treatment of rising glycaemia late in the second trimester. However, recent evidence challenges this view. Pre-pregnancy and pregnancy-specific factors influence gestational glycaemia, with open questions regarding roles of non-glycaemic factors in the aetiology and consequences of gestational diabetes. Varying patterns of insulin secretion and resistance in early and late pregnancy underlie a heterogeneity of gestational diabetes in the timing and pathophysiological subtypes with clinical implications: early gestational diabetes and insulin resistant gestational diabetes subtypes are associated with a higher risk of pregnancy complications. Metabolic perturbations of early gestational diabetes can affect early placental development, affecting maternal metabolism and fetal development. Fetal hyperinsulinaemia can affect the development of multiple fetal tissues, with short-term and long-term consequences. Pregnancy complications are prevented by managing glycaemia in early and late pregnancy in some, but not all women with gestational diabetes. A better understanding of the pathophysiology and heterogeneity of gestational diabetes will help to develop novel management approaches with focus on improved prevention of maternal and offspring short-term and long-term complications, from pre-conception, throughout pregnancy, and beyond.

Chrononutrition studies the relation between diet, circadian rhythms and metabolism, which may alter the metabolic intrauterine environment, influencing infant fat-mass (FM) development and possibly increasing obesity risk.

To evaluate the association of chrononutrition in pregnancy and infant FM at 6 months.

Healthy pregnant women and term-babies (n = 100pairs) from the OBESO cohort (2017-2023) were studied. Maternal registries included pregestational body-mass-index (BMI), gestational complications/medications, weight gain. Diet (three 24 h-recalls, 1 each trimester) and sleep-schedule (first and third trimesters) were evaluated computing fasting (hours from last-first meal), breakfast and dinner latencies (minutes between wake up-breakfast and dinner-sleep, respectively), number of main meals/day, meal skipping (≥1 main meal/d on three recalls) and nighttime eating (from 9:00 pm-5:59 am on three recalls). Neonatal weight, length, BMI/age were assessed. At 6 months, infant FM (kg, %; air-displacement plethysmography) was measured, and FM index (FMI-kgFM/length2) computed. Exclusive breastfeeding (EBF) was recorded. Multiple linear regression models evaluated the association between chrononutrition and 6 month infant FM.

Mean fasting was 11.7 ± 1.3 h; breakfast, dinner latency were 87.3 ± 75.2, 99.6 ± 65.6 min, respectively. Average meals/day were 3.0 ± 0.5. Meal skipping was reported in 3% (n = 3) of women and nighttime eating in 35% (n = 35). Most neonates had normal BMI/age (88%, n = 88). Compared to those who did not, mothers engaged in nighttime-eating had infants with higher %FM (p = 0.019). Regression models (R 2 ≥ 0.308, p ≤ 0.001) showed that nighttime eating was positively associated with %FM (B: 2.7, 95%CI: 0.32-5.16). When analyzing women without complications/medications (n = 80), nighttime eating was associated with higher FM [%FM, B: 3.24 (95%CI: 0.59-5.88); kgFM, B: 0.20 (95%CI: 0.003-0.40); FMI, B: 0.54 (95%CI: 0.03-1.05)]. Infant sex and weight (6 months) were significant, while maternal obesity, pregnancy complications/medications, parity, energy intake, birth-BMI/age, and EBF were not.

Maternal nighttime eating is associated with higher adiposity in 6 month infants.

Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF-1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast-specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short- and long-term consequences of abnormal fetal growth in the future.

Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats.

For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1-PND5). The offspring were evaluated at PND45.

MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status.

Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life.

Endocannabinoids and their N-acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed in utero to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this cross-sectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth.

Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated.

Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM- women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (β=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring.

The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM- women and was associated with GDM+ offspring growth at 2 months.

ClinicalTrials.gov, identifier (NCT04263675 and NCT02872402).