In a multinational randomized controlled trial, we previously showed that maternal supplementation with myo-inositol, probiotics, and micronutrients was associated with reduced incidence of rapid infant weight gain and high body mass index (BMI) at two years among offspring. It was unclear whether these differences in weight gain and body mass were due to reduced adiposity. Therefore, we aimed to determine whether there were any differences in body composition.

Body composition was measured using bioelectrical impedance spectroscopy at six weeks, six months, one year, and two years among offspring born to mothers who received a nutritional intervention (n = 268) or control (n = 264) supplement preconception and during pregnancy.

There were no group-level differences in body composition, except at two years, when fat-free mass was greater among control offspring [adjusted mean difference (aMD) 0.14 kg, 95% confidence interval (CI) 0.03, 0.25, P = 0.012]. However, there were no differences in mean percentage fat mass (%FM) at any time. In both groups, rapid weight gain [Δ weight > 0.67 standard deviation (SD) from birth to one year] was associated with greater %FM (aMD 2.0% at six months, 2.0% at one year, 1.4% at two years) compared with those who did not have rapid weight gain. Likewise, high BMI (≥ 95 percentile) at two years was associated with greater %FM (aMD 2.5%).

A maternal nutritional intervention did not lead to differences in average offspring body composition in the first two years of life. However, fewer offspring from the supplemented group experienced rapid weight gain and high BMI, characterized by greater %FM.

In clinical populations, vitamin B12 deficiency has been associated with adverse metabolic health (e.g., gestational diabetes). Population-level data among women of reproductive age could inform screening and interventions. The objective of this analysis was to examine the prevalence of adverse metabolic characteristics (elevated adiposity and central adiposity, hypertension, elevated glycated hemoglobin [HbA1c]) and associations of vitamin B12 status with metabolic characteristics in women as part of a population-based biomarker survey in Southern India.

Participants (n = 980 women 15-40 y; not pregnant or lactating) were assessed for total vitamin B12, holotranscobalamin, methylmalonic acid, homocysteine, and HbA1c. Categorical anthropometry assessments and bioelectrical impedance analysis (e.g., whole body (WF%) and trunk (TF%) fat) were assessed among adults (≥18 y). Linear and binomial regressions were used to examine associations of vitamin B12 status with metabolic characteristics.

Overall, 25 % of participants had HbA1c ≥5.7 % (HbA1c ≥5.7-<6.5 %: 20.0 %; ≥6.5 %: 5.0 %), and 18.6 % had hypertension (Stage 1: 16.4 %; Stage 2: 2.2 %). Among adults, 23.4 % had body mass index of (BMI) 25.0-<30.0 kg/m2, 9.6 % had BMI ≥30.0 kg/m2, 13.4 % had elevated waist circumference (WC; >88.9 cm), and 20.8 % had elevated waist-hip ratio (WHR; ≥0.85 cm). Overall, higher vitamin B12 concentrations were associated with lower BMI and WC. Among adults, higher vitamin B12 concentrations were associated with lower WF% and TF%; and lower prevalence of overweight (BMI ≥25.0 kg/m2) and elevated WC, WHR, and WF%. Similarly, vitamin B12 <148 pmol/L was associated with higher BMI and WC overall and, among adults, higher WF% and TF%, and increased overweight (BMI ≥25.0 kg/m2; prevalence ratio: 1.31; 95 % confidence interval: 1.09-1.58), and elevated WC (>88.9 cm; 1.85 [1.32-2.60]), WHR (≥85.0; 1.38 [1.07-1.78]), WF% (>35 %; 1.29 [1.10-1.51]), and TF% (>35 %; 1.25 [1.06-1.49]).

The burden of adverse metabolic characteristics was substantial in this population of young, apparently healthy women. Among those with vitamin B12 <148 pmol/L there was increased central adiposity and overweight status. Evaluating vitamin B12 and metabolic outcomes prospectively could inform screening and interventions to improve women's health.

NCT04048330.

Maternal high level of folate and low level of vitamin B12, namely "folate and vitamin B12 imbalance", has been found to be associated with metabolic disorders, such as gestational diabetes mellitus (GDM). The aims of this study were to explore the associations of maternal serum folate, vitamin B12 and their imbalance in early pregnancy with GDM, and to explore the potential mediation effects of the methionine cycle related metabolites on the above associations.

This nested case-control study (172 GDM case-control pairs) was conducted based on a prospective birth cohort. Serum concentrations of 5-methyltetrahydrofolate (5-MTHF), vitamin B12 and methionine cycle related metabolites [S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and Homocysteine (Hcy)] were detected. 5-MTHF (nmol/L)/vitamin B12 (pmol/L) times 1000 was calculated to indicate the imbalance status of folate and vitamin B12. Conditional logistic regression was performed to analyze the associations of 5-MTHF, vitamin B12 and their imbalance with GDM. The mediation effect models were applied to explore the mechanism.

High serum level of 5-MTHF in early pregnancy was related to a higher risk of GDM (OR = 2.00, 95%CI: 1.19-3.37). Compared with the group of the lowest tertile concentration of vitamin B12, the group of the highest concentration had a lower risk of GDM (OR = 0.33, 95%CI: 0.11-0.97). Higher 5-MTHF/vitamin B12 was associated with a higher risk of GDM (OR = 1.67, 95%CI: 1.08-2.56). Besides, no significant mediation effect of methionine cycle related metabolites was found on the associations of folate, vitamin B12 and the imbalance status with the risk of GDM.

High maternal serum folate, low vitamin B12 levels and the resulting imbalance may increase the risk of GDM. The theory of "folate trap" could not explain the effect of folate, vitamin B12 and their imbalance on GDM.

Folate, an essential water soluble vitamin B9 that cannot be synthesized naturally by the bodily function. Dietary sources or probiotic-folates are the two biological modes for acquiring the target vitamin which aids DNA synthesis and repair. Probiotics are known for their divergent health benefits and have garnered significant interest. Particularly in microbial strains that produce folate offers a promising way to enhance the level of folate. Notably, folate-producing probiotic strain includes Lactiplantibacillus, Lactococcus, Bifidobacterium, and Streptococcus. As an emerging source of health benefits, folate producing probiotics helps in improving the gut microbiota for overall well-being of human body. On the other side, chemically synthesized folic acid were not highly advantageous as they lacks absorption, conversion and excretion. Hence, usage of microbial-folate are safer as it can easily undergo absorption and reduces severe side effects. The present review mainly focus on folate one-carbon metabolism, its significance in human health, folate deficiency and malabsorption, adverse effects and folate synthesis from probiotic bacterial strains, and also toxicological impacts. In particular, the beneficiary role of these probiotic strains were found to be associated with therapeutic applications in several diseases such as autoimmune disorder, metabolic disorders, and cardiovascular diseases (CVDs), wound healing, drug delivery and cancer.

Methionine, an essential sulfur-containing amino acid, plays a critical role in methyl metabolism, folate metabolism, polyamine synthesis, redox homeostasis maintenance, epigenetic modification and signaling pathway regulation, particularly during embryonic development. Animal and human studies have increasingly documented that methionine deficiency or excess can negatively impact metabolic processes, translation, epigenetics, and signaling pathways, with ultimate detrimental effects on pregnancy outcomes. However, the underlying mechanisms by which methionine precisely regulates epigenetic modifications and affects signaling pathways remain to be elucidated. In this review, we discuss methionine and the metabolism of its metabolites, the influence of folate-mediated carbon metabolism, redox reactions, DNA and RNA methylation, and histone modifications, as well as the mammalian rapamycin complex and silent information regulator 1-MYC signaling pathway. This review also summarizes our present understanding of the contribution of methionine to these processes, and current nutritional and pharmaceutical strategies for the prevention and treatment of developmental defects in embryos.

Emerging research suggests that the intrauterine environment plays a critical role in predisposing individuals to metabolic syndrome (MetS), a constellation of conditions that heightens the risk for heart disease, stroke, and diabetes. Traditionally linked to lifestyle, the risk for MetS is now understood to be also influenced by fetal exposures. The environment in which a child lives offers abundant potential sources that can contribute to an increased risk of developing various diseases, and in some cases, these factors can be avoided. This review integrates findings from both epidemiological and experimental research to underscore the impact of prenatal factors, including maternal nutrition, obesity, gestational diabetes (GDM), and birth size, on the subsequent development of metabolic derangements in offspring, particularly during puberty. The progression of genetic and epigenetic studies has enlightened the pathophysiology of these conditions starting in the intrauterine period and continuing into early life. By examining data and studies, this article elucidates the prenatal influences and underlying mechanisms that contribute to the pathogenesis of MetS. The updated understanding of the link between the intrauterine environment and future health comorbidities will draw attention to intrauterine care and maternal health and contribute to the prevention of serious diseases in adulthood.

Malnutrition during pregnancy is associated with adverse birth outcomes, but the importance of maternal diet during pregnancy for neonatal body composition remains inconclusive. This study investigated the role of maternal diet during pregnancy for neonatal body composition in the Ethiopian iABC birth cohort.

The data stemmed from the first visit at birth comprising 644 mother-child pairs. Shortly after delivery, the diet of the last week of pregnancy was assessed by a non-quantitative and non-validated 18-items food frequency questionnaire. Multiple imputation was used to handle missing data. Twin births and implausible values were excluded from analysis (n = 92). The Dietary Diversity Score (0-9 points) was constructed and exploratory dietary patterns were derived via principal component analysis. Neonatal fat mass and fat-free mass were assessed by air-displacement plethysmography. The associations of maternal Dietary Diversity Score and exploratory dietary patterns with gestational age, neonatal anthropometric measures and body composition were investigated using multiple-adjusted linear regression analysis.

In this cohort (n = 552), mean ± standard deviation (SD) mother's age was 24.1 ± 4.6 years and the median maternal Dietary Diversity Score was 6 (interquartile range = 5-7). An 'Animal-source food pattern' and a 'Vegetarian food pattern' were identified. The mean ± SD birth weight was 3096 ± 363 g and gestational age was 39.0 ± 1.0 weeks. Maternal adherence to the Animal-source food pattern, but not Vegetarian food pattern, was related to birth weight [79.5 g (95% confidence interval (CI): -14.6, 173.6)]. In the adjusted model, adherence to the Animal-source food pattern was associated with higher neonatal fat-free mass [53.1 g (95% CI: -20.3, 126.6)], while neonates of women with high compared to low adherence to Dietary Diversity Score and Vegetarian food pattern had higher fat mass [19.4 g (95% CI: -7.4, 46.2) and 33.5 g (95% CI: 2.8, 64.1), respectively].

In this Ethiopian population, maternal diet during pregnancy was associated with neonatal body composition. The analysis of body composition adds important detail to the evaluation of maternal dietary habits for the newborn constitution.

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.

Objective: To assess the association between maternal iron, folic acid and combined iron-folic acid (IFA) oral supplementation during pregnancy and childhood obesity markers in 9- to 13-year-olds. Methods: Data from the 2007-2009 Healthy Growth Study were analysed. The study assessed obesity markers, i.e., body mass index (BMI), skinfold thickness and waist circumference. The research question was examined using generalised linear models stratified by the child's sex, maternal prepregnancy weight and gestational age. Results: Folic acid and IFA supplements, but not iron alone, were significantly associated with lower waist circumference in all children (coef. -1.35, 95% CI: -2.47 to -0.23; coef. -1.01, 95% CI: -2.21 to -0.23, p < 0.05). These associations were observed only in girls with lower BMI (coef. -0.88), skinfold thickness (coef. -4.92) and waist circumference (coef. -2.99) with folic acid and similar IFA effects. Interestingly, in boys born to obese mothers before pregnancy, a significant negative association was observed for folic acid alone with BMI (coef. -3.55) and waist circumference (coef. -7.09) and IFA for the sum of skinfold thickness (coef. -19.68). Conclusion: Maternal folic acid and IFA supplementation may contribute to a lower likelihood of childhood obesity, especially in girls and children of underweight or obese mothers, emphasising the importance of proper prenatal nutrition.

Maternal nutritional deficiency is linked with several adverse outcomes in offspring but the link between maternal vitamin B12 levels and offspring schizophrenia remains unexplored.

In this nationwide population-based nested case-control design, 1145 schizophrenia cases were born between 1987-1997 and diagnosed by 2017 and each case were matched with a control. Maternal vitamin B12 levels during the first and early second trimesters of pregnancy were measured using chemiluminescence microparticle immunoassay from maternal sera. Conditional logistic regression was used to examine the association between maternal vitamin B12 levels and offspring schizophrenia.

Low maternal vitamin B12 levels were not associated with offspring schizophrenia in unadjusted (OR 1.04, 95% CI 0.88-1.24) or adjusted analyses (aOR 1.14, 95% CI 0.95-1.37). When analyzed by quintiles, no significant association was observed between the lowest versus highest quintile of maternal vitamin B12 levels and schizophrenia in unadjusted (OR 1.01, 95% CI 0.78-1.30) or adjusted analyses (OR 0.89, 95% CI 0.68-1.17).

Maternal vitamin B12 levels in early pregnancy were not associated with offspring schizophrenia. Future studies measuring both genetic and environmental factors are required to elucidate the role of maternal vitamin B12 deficiency in schizophrenia and its potential pathways to influence schizophrenia in offspring.

South Asia has high prevalence rates of type 2 diabetes (T2D). Until the 1990s, the prevalence of T2D within South Asia was low but much higher in the South Asian diaspora living abroad. Today, high prevalence rates of T2D are reported among those living in South Asia. T2D in South Asians presents with unique clinical features described as the "South Asian phenotype" that include younger age at onset of diabetes than in White Europeans, much lower BMI, hyperinsulinemia and greater insulin resistance, rapid decline in β-cell function resulting in low insulin reserve, low muscle mass, and greater ectopic fat deposition, especially in the liver. Also, prevalence of impaired fasting glucose is higher among South Asians than prevalence of impaired glucose tolerance. Genetic predisposition combined with intrauterine fetal programming (low vitamin B12 intake and high folate intake) increases susceptibility to T2D, from birth. In later life, overnutrition, especially a high carbohydrate intake with refined grains of higher glycemic index, coupled with low physical activity likely triggers the T2D epidemic in South Asians. Additionally, there are emerging risk factors like air pollution. Preventing T2D in South Asians requires a multifactorial approach, including improvements in maternal and fetal nutrition with special reference to vitamin B12 and folate intake, decreasing refined carbohydrate and increasing protein and fiber intake in the diet, increasing physical activity, and control of air pollution. Lessons learned from epidemiology of T2D in South Asians could be useful to other developing countries that are in earlier stages of epidemiological transition.

Folate and B12, among other B vitamins, are methyl donors and contribute to multiple DNA methylation processes. Maternal deficiency of these nutrients may be associated with impaired fetal growth, affecting the nutritional status and adiposity of the newborn. This study aimed to describe maternal folate and B12 status throughout pregnancy and evaluate its association with neonatal nutritional status.

We studied 90 healthy pregnant women and their babies from the prospective OBESO cohort (Mexico City). Serum folate and B12 concentrations were measured (ELISA) in the first and third trimesters of pregnancy. Deficiency was considered if serum folate was <4 ng/mL, red blood cell folate (RBC) < 151 ng/mL, active B12 < 40 pmol/L, and total B12 < 203 pg/mL). Maternal supplementation of these nutrients was recorded. Newborn assessment (24-72 h) included weight (BW), length (L), waist circumference (WC), and fat mass percentage (%FM; air-displacement plethysmography). Newborn nutritional status indexes were computed and interpreted (BMI/age and length/age) (term-WHO, preterm-Intergrowth). Mean differences, correlations, and multiple linear and logistic regressions were performed (SPSS v. 29).

One-third of women had total vitamin B12 deficiency at the end of pregnancy; no folate deficiency was observed. High doses for both folic acid and B12 supplementation were identified in the third trimester (2057.04 ± 2100.74 μg/d and 7.35 ± 4.56 μg/d). Higher first- and third-trimester maternal active B12 concentrations predicted higher WC and reduced the risk of LBW. Higher first-trimester Thcy levels increased the risk of stunting. Higher third-trimester total B12 and folate concentrations predicted higher WC; the latter was associated with higher FM% at birth.

Maternal folate, B12, and Thcy levels influence newborn nutritional status alterations, including adiposity markers. It is vital to guarantee an optimal and balanced maternal B-complex status throughout pregnancy.

Maternal nutrition promotes maternal and child health. However, most interventions to address undernutrition are only implemented once pregnancy is known, and cannot address broader risk factors preceding conception. Poverty and socio-economic status are considered systemic risk factors, but both economic growth and cash transfers have had limited success improving undernutrition. Another generic risk factor is low human capital, referring to inadequate skills, knowledge and autonomy, and represented by traits such as low educational attainment and women's early marriage. Few studies have evaluated whether maternal human and socio-economic capital at conception are independently associated with maternal and offspring outcomes.

Using data on 651 mother-child dyads from the prospective Pune Maternal Nutrition Study in rural India, composite markers were generated of "maternal human capital" using maternal marriage age and maternal and husband's education, and 'socio-economic capital' using household wealth and caste. Linear and logistic regression models investigated associations of maternal low/mid human capital, relative to high capital, with her own nutrition and offspring size at birth, postnatal growth, education, age at marriage and reproduction, and cardiometabolic risk at 18 years. Models controlled for socio-economic capital, maternal age and parity.

Independent of socio-economic capital, and relative to high maternal human capital, low human capital was associated with shorter maternal stature, lower adiposity and folate deficiency but higher vitamin B12 status. In offspring, low maternal human capital was reflected in shorter gestation, smaller birth head girth, being breastfed for longer, poor postnatal growth, less schooling, lower fat mass and insulin secretion at 18 years. Daughters married and had children at an early age.

Separating maternal human and socio-economic capital is important for identifying the aspects which are most relevant for future interventions. Low maternal human capital, independent of socio-economic capital, was a systemic risk factor contributing to an intergenerational cycle of disadvantage, perpetuated through undernutrition, low education and daughters' early marriage and reproduction. Future interventions should target maternal and child human capital. Increasing education and delaying girls' marriage may lead to sustained intergenerational improvements across Sustainable Development Goals 1 to 5, relating to poverty, hunger, health, education and gender equality.

Globally in 2024, 1 in 5 women aged 20-24 years worldwide had been married before the age of 18 years. One reason for this persistent prevalence of underage marriage may be the slow change in social norms relating to education levels and women's marriage age. However, we know little about how norms change, and whether they vary by socio-demographic characteristics. We aimed to investigate changes in social norms across generations in rural Maharashtra, India.

To understand the status quo, we identified education levels and marriage ages typical of contemporary young adults in rural Maharashtra using the National Family Health Survey. To see if norms have shifted across generations, we analysed data on education and marriage age in 659 parent-adolescent dyads from the Pune Maternal Nutrition Study (PMNS) in rural Maharashtra. To ascertain if norms might shift in the future, we investigated adolescents' aspirations for their future hypothetical children's education and marriage, and classified adolescents as wanting (a) their children to decide themselves, (b) more education and later marriage age, or (c) the status quo. We assessed whether these aspirations differed by socio-demographic characteristics.

Compared to the status quo and PMNS adults, PMNS adolescents had substantially more education, and girls were marrying slightly later. About 70% of the adolescents wanted their children to themselves decide their schooling. The remainder of both sexes wanted their children to have the same education as them (15 years). Only 10% of adolescent girls and 14% of boys wanted their child to decide their own marriage age. Most adolescents wanted a later marriage age for their children than their own experience. Lower educated and early married girls aspired for greater education for their children. More educated boys aspired for later marriage for their children.

Education norms have changed by a larger magnitude than marriage age norms. Adolescents are already attaining their education aspirations, but aspire for later marriage of their children, more so for their hypothetical sons than daughters. Since senior household members remain influential in marriage decisions, it may take time before adolescents' aspirations for their children become a new norm.

Like in many developing countries, the traditional Ethiopian diet relies mainly on starchy staple foods and often lacks sufficient animal-sourced foods which are crucial for cobalamin intake. Furthermore, the concentration of folate in traditionally prepared injera, an Ethiopian cereal-based fermented staple food, is highly variable and injera contains biologically inactive corrinoids. This study aimed to improve the cobalamin and folate content of injera by using cobalamin-producing Propionibacterium freudenreichii and folate-producing Lactiplantibacillus plantarum strains, both individually and combined. Since injera is fermented using backslopping, we also assessed the ability of these strains to produce cobalamin and folate consistently across successive fermentation batches. Changes in the microbial ecosystem were monitored using real-time PCR. The theoretical contribution of the injera prepared using the selected strains to the cobalamin and folate intake of children and women of reproductive age was also calculated. Results showed that using the selected bacterial strains individually increased cobalamin (up to 19.2 μg/100 g of dry matter) and folate (up to 180.2 μg/100 g of dry matter) levels in the injera dough over several backslopping fermentation batches. Regular consumption of the injera with enhanced vitamin content produced using each strain alone would be capable of fulfilling the entire recommended nutrient intake for cobalamin and up to 29 % of the recommended intake for folate for children and women of reproductive age. However, when the strains were used together, the production of both vitamins was reduced. The presence of certain common endogenous bacterial species and genera exhibited significant variability, highlighting the complex response of the native microbiota to the different inoculation strategies employed. Future experiments should consider selecting a microbial consortium comprising non-competing microorganisms to ensure the simultaneous production of cobalamin and folate in fermented foods.

Early-life exposures including diet, and the gut microbiome have been proposed to predispose infants towards multifactorial diseases later in life. Delivery via Cesarian section disrupts the establishment of the gut microbiome and has been associated with negative long-term outcomes. Here, we hypothesize that Cesarian section delivery alters not only the composition of the developing infant gut microbiome but also its metabolic capabilities. To test this, we developed a metabolic modeling workflow targeting the infant gut microbiome.

The AGORA2 resource of human microbial genome-scale reconstructions was expanded with a human milk oligosaccharide degradation module. Personalized metabolic modeling of the gut microbiome was performed for a cohort of 20 infants at four time points during the first year of life as well as for 13 maternal gut microbiome samples.

Here we show that at the earliest stages, the gut microbiomes of infants delivered through Cesarian section are depleted in their metabolic capabilities compared with vaginal delivery. Various metabolites such as fermentation products, human milk oligosaccharide degradation products, and amino acids are depleted in Cesarian section delivery gut microbiomes. Compared with maternal gut microbiomes, infant gut microbiomes produce less butyrate but more L-lactate and are enriched in the potential to synthesize B-vitamins.

Our simulations elucidate the metabolic capabilities of the infant gut microbiome demonstrating they are altered in Cesarian section delivery at the earliest time points. Our workflow can be readily applied to other cohorts to evaluate the effect of feeding type, or maternal factors such as diet on host-gut microbiome inactions in early life.

The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = - 0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = - 0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development.

The developmental origins of health and disease hypothesis propose that lifelong health is programmed during foetal development, in utero. The world's population is ageing due to increased longevity but expanding morbidity and the associated burden on health systems around the planet, are associated with this. Consequently, resources are strained and spent largely on treating patients rather than preventing chronic diseases at their source. Research on early life exposures, starting in the womb, is needed to identify new potential biomarkers linked with the development of chronic diseases during adulthood. Evidence from maternal-offspring cohorts investigating associations between pregnancy exposures and childhood metabolic health is reviewed (The GUSTO study in Singapore, the Copenhagen Prospective Studies on Asthma in Childhood, a mother-child cohort in rural Gambia, the MINIMat study in Bangladesh, The Iodine Status in Pregnancy and Offspring Health Cohort in China, the OBESO cohort in Mexico, the Pune Nutrition study in India, The Reus-Tarragona Birth Cohort study in Spain). Collectively, evidence from prospective observational studies, randomised controlled trials and animal studies, supports the hypothesis that maternal diet, lifestyle and nutritional status during pregnancy are associated with childhood metabolic health in the offspring. However, the evidence is scant and further research is needed.

Vitamin B12 deficiency is a prevalent condition affecting a significant proportion of India's population, with implications for mental health. Despite its established link to psychiatric symptoms, vitamin B12 deficiency often remains underdiagnosed. The aim of this study is to highlight the association between vitamin B12 deficiency and acute psychosis, emphasizing the importance of early detection and treatment.

This is a retrospective case series with inclusion criteria of diagnosis of Acute and Transient Psychotic Disorder (ATPD) and associated vitamin B12 Deficiency over the past five years. Patients with comorbid psychiatric illnesses and substance use other than nicotine, hematological and neurological symptoms associated with vitamin B12 deficiency and significant life stressors prior to onset of illness were excluded from the study. A review of electronic medical records of all these patients was done. Out of these patients, eight cases satisfied the study selection criteria.

Sociodemographic, investigation, and treatment details of all eight patients are presented. All of them received low-dose antipsychotics and vitamin B12 replacement therapy, resulting in significant improvement. Vegetarian dietary habits were identified as a common risk factor.

Vitamin B12 deficiency can manifest solely as ATPD, particularly in individuals following vegetarian diets. Early detection and treatment are crucial to prevent irreversible psychiatric and neurological damage. Routine vitamin B12 level assessments are recommended in patients with mental and psychiatric disturbances.

Obesity paradox refers to the clinical observation that when acute cardiovascular decompensation occurs, patients with obesity may have a survival benefit. This apparently runs counter to the epidemiology of obesity, which may increase the risk for non-communicable diseases (NCDs). The scientific community is split on obesity paradox, with some supporting it, while others call it BMI paradox. This review: (a) defines the obesity paradox, and its proposed role in overall mortality in NCDs; (b) delineates evidence for and against obesity paradox; (c) presents the importance of using different indices of body mass to assess the risk in NCDs; (d) examines the role of metabolically healthy obesity in obesity paradox, and emerging importance of cardio-respiratory fitness (CRF) as an independent predictor of CVD risk and all-cause mortality in patients with/without obesity. Evidence suggests that the development of obesity and insulin resistance are influenced by genetic (or ethnic) make up and dietary habits (culture) of the individuals. Hence, this review presents lean diabetes, which has higher total CVD and non-CVD mortality as compared to diabetics with obesity and the possibility of maternal factors programming cardiometabolic risk during fetal development, which may lead to a paradigm shift in our understanding of obesity.

The prevalence of neural tube defects (NTDs) is higher in Ethiopia than most other countries, and ~84% of Ethiopian women of reproductive age (WRA) have folate insufficiency, a major risk factor for NTDs. Salt fortification with folic acid is a potential strategy to improve women's folate status, but data are needed on the acceptability, nutritional impact and safety of folic acid fortification of iodised salt.

The study is designed as a community-based, household-randomised, dose-response trial. A total of 360 non-pregnant WRA 18-49 years of age will be randomly assigned to one of three intervention arms: (1) iodised salt fortified with 30 ppm folic acid to provide ~200 µg folic acid/day; (2) iodised salt fortified with 90 ppm folic acid to provide ~600 µg folic acid/day; or (3) iodised salt (comparator). The preweighed salts will be delivered to participants' homes biweekly for 26 weeks; unused salt will be collected and weighed. Fasting, venous blood samples will be collected at baseline, end line and a randomly assigned intermediate time point for assessment of folate, iodine, vitamin B12 and other micronutrient status biomarkers. Women's dietary intakes, including discretionary salt consumption, will be measured using weighed food records; 24-hour urine specimens will be analysed for sodium and iodine excretion. Primary outcomes are women's consumption of study salts, change in biomarkers of folate and iodine status and prevalence of adverse events. Results will be analysed using analysis of covariance models to estimate group mean differences for continuous outcomes, controlling for baseline measurements, and log-binomial or modified Poisson regressions for categorical outcomes. Prespecified effect modifications will be explored.

The study has been approved by the Ethiopian Public Health Institute's Institutional Review Board, and the protocol has been registered with ClinicalTrials.gov (registration number NCT06223854). Study results will be published in open access scientific journals and disseminated nationally in Ethiopia.

NCT06223854.

Folates play a crucial role as cofactors in metabolic pathways, influencing biological methylation and nucleotide synthesis, which has a significant impact on overall health and disease susceptibility. Diabetic nephropathy (DN) is a prevalent and severe complication of diabetes mellitus (DM). The correlation between RBC folate and DN remains unclear currently. This study aims to assess whether RBC folate is associated with DN. Based on data from the NHANES (2011-2018), we conducted a cross-sectional study involving 3070 adults with type 2 DM (T2DM). Demographic factors, levels of folate and vitamin B12, dietary folate intakes, and relevant laboratory data were obtained from all participants. Logistic regression, fitting smooth curves, interaction effects were utilized to support the research objectives. Regression analyses demonstrated a positive relation between RBC folate and DN. (P < 0.001). A positive association between levels of RBC folate and the risk of DN was observed after full adjustment for all the confounding variables (odds ratio: 1.38, 95% confidence interval: 1.27-1.49, P < 0.001). Similar patterns of association were observed for subgroup analysis (all P values for interaction > 0.05). In addition, curve fitting after adjusting for all the confounding variables demonstrated that there was a linear relationship between RBC folate and DN (P for non-linearity = 0.147). Increased RBC folate levels were linked to a higher risk of DN in type 2 diabetes. RBC folate should be considered as a crucial indicator for folate status in DN.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing no FA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and 1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.

Postprandial glycemic fluctuations after gastrectomy are seen in patients with gastric cancer but, no studies have investigated the association between gastrectomy and type 2 diabetes mellitus (T2DM) in gastric cancer survivors. This study aimed to elucidate the relationship between gastrectomy (total or subtotal) and incident T2DM. In addition, we explored whether vitamin B12 supplementation modulates this risk among patients who have undergone total gastrectomy.

In this large nationwide population-based retrospective cohort study using the National Health Insurance Service database of South Korea, we identified patients aged >20 years who underwent gastrectomy from 2008 to 2015 (n = 150,074) and age- and sex-matched controls without gastrectomy (n = 301,508). A Cox proportional hazards model was used.

During the median follow-up duration of 4.4 years after the 2-year time lag after gastrectomy, of the 78,006 subjects, 4,597 (5.9 %) developed T2DM. Compared with matched controls, the adjusted hazard ratio (AHR[95 % confidence interval]) for T2DM of patients with total gastrectomy was 1.34[1.23;1.47]. The corresponding AHR after subtotal gastrectomy was 0.81[0.76;0.86]. Among the patients with total gastrectomy, the risk of T2DM was significantly increased in those who did not receive any vitamin B12 supplementation (AHR=1.60[1.33;1.92]), whereas the risk of T2DM was lower (close to being statistically significant) in those who received continuous vitamin B12 supplementation after gastrectomy (AHR=0.70[0.49;1.01]).

These results show a significantly reduced risk of T2DM in gastric cancer patients undergoing subtotal gastrectomy and a significantly increased risk of T2DM in gastric cancer patients undergoing total gastrectomy, which is mitigated by continuous vitamin B12 supplementation.

This study evaluated the effect of an altered ratio of maternal RBC folate (MRF) to serum vitamin B12 (MB12) on pregnancy and newborn outcomes.

Blood samples were collected from pregnant women and the umbilical cord at the time of delivery. Estimations of RBC folate and serum vitamin B12 from maternal and cord blood samples and total homocysteine (HCY) were performed. Maternal and newborn anthropometric parameters like placental weight (PW), head circumference (HC), chest circumference (CC), and body weight (BW) were measured in offsprings after birth. We stratified the pregnant women into six groups (a) vitamin B12 normal and folic acid normal (BNFN)-control group, (b) vitamin B12 normal and folic acid elevated (BNFE), (c) vitamin B12 normal and folic acid deficient (BNFD), (d) vitamin B12 deficient and folic acid normal (BDFN), (e) vitamin B12 deficient and folic acid elevated (BDFE) and (f) vitamin B12 deficient and folic acid deficient (BDFD) based on their levels of RBC folate (MRF) and vitamin B12 (MB12). The expression of the one-carbon metabolism genes (methionine synthase (MS), glycine N-methyltransferase (GNMT), and cystathionine β-synthase (CBS) was also studied in placental tissue by using real-time PCR.

Cord blood RBC folate was significantly reduced in groups BDFE and BDFD as compared to the control group (BNFN). The cord blood vitamin B12 levels were also reduced in the BDFE group as compared to the BDFD. All the newborn parameters viz. PW, HC, CC, and BW, were reduced in the altered MRF/MB12 ratio (low & high vs. normal ratio). Total HCY was significantly elevated in the groups with (BDFE & BDFN) an imbalance of maternal RBC folate and serum vitamin B12 as compared to the control group. Downregulation of one-carbon metabolism genes like MS (p < 0.001), GNMT (p < 0.05), and CBS (p < 0.01) in placental tissue was observed in the high MRF/MB12 ratio group as compared to the normal ratio group. A strong positive correlation was also observed between MRF, MB12, and newborn parameters.

The altered ratio of folate to vitamin B12 in the maternal blood is associated with adverse growth and development of the newborn.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.

Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by transgenerationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for gestation-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish an exposure threshold due to nutrient deficiencies or other environmental factors that can result in clinically relevant epigenetic alterations that modulate disease risks in the fetus. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development. This review unravels the potential roles of the functional epigenome for targeted intervention to ensure optimal fetal brain development and its performance in later life.

Association between vitamin B12 deficiency (VB12D) and dietary patterns being well documented has bearing on obstetrics and neonatal outcomes. However, relationship between VB12D and serum inflammatory markers (IMs), particularly in vegetarian diet and Polycystic ovary syndrome (PCOS), remains elusive. This cross-sectional study assesses VB12D and IMs among reproductive age women consuming different diets.

Nonvegetarian (PCOS, n = 104; healthy, n = 148) and vegetarian women (PCOS n = 112; healthy, n = 186) are for evaluated clinical, biochemical, hormonal assessment, inflammatory, and four vitamin B 12 (VB12) markers. VB12D is defined by Fedosov's wellness quotient (4cB12). Using 4cB12, prevalence of VB12D is discerned in 54.4% (PCOS: 72.1%; healthy 36.5%) and 93.4% (PCOS: 95.9%; healthy: 91.9%) among nonvegetarians and vegetarians, respectively. Vegetarian PCOS women depict lowest median (interquartile range [IQR]) of serum B12 76.2(72.6) pg mL-1, holotranscobalamine (HTC) 37.9(11.3) and highest homocysteine (HCY) 40.32(6.0) µmol L-1, methylmalonic acid (MMA) 352.26(156.7) nmol L-1 with highest Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and IMs (Monocyte chemoattractant protein 1 (MCP-1), High sensitivity C-reactive protein (hs-CRP), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 6 (IL-6)). Significant correlation of serum hs-CRP, TNF-α, and IL-6 with VB12 markers is observed.

The VB12D is rampant among reproductive age women that gets exacerbated by PCOS or vegetarian diet. It is directly correlated with magnitude of proinflammatory markers. The results carry substantial implications for public health policies aimed at improving preconception maternal VB12 status for better future pregnancy and offspring outcomes.

Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources.

However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring. Low cobalamin status in pregnancy has been associated with similar outcomes as those reported in the Indian studies although the evidence is scant and conflicting.

Consideration should be given to maternal cobalamin status in the context of prevention of adverse pregnancy outcomes as well as cobalamin insufficiency both in the mother and the offspring during lactation. Further attention is now justified with the increasing tendency toward plant-based diets. Reference intervals for cobalamin status during each trimester of pregnancy are needed and further investigation of the long-term conse-quences of low cobalamin status during pregnancy for health and development in the offspring is warranted.

The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years.

We followed 8500 T1D-susceptible children born in the U.S., Finland, Sweden, and Germany in 2004 -2010 from the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is a prospective observational birth cohort. Dietary intake of seven B vitamins was calculated from foods and dietary supplements based on 24-h recall at 3 months and 3-day food records collected regularly from 6 months to 10 years of age. Cox proportional hazard models were adjusted for energy, HLA-genotype, first-degree relative with T1D, sex, and country.

A total of 778 (9.2) children developed at least one autoantibody (any IA), and 335 (3.9%) developed multiple autoantibodies. 280 (3.3%) children had IAA and 319 (3.8%) GADA as the first autoantibody. 344 (44%) children with IA progressed to T1D. We observed that higher intake of niacin was associated with a decreased risk of developing multiple autoantibodies (HR 0.95; 95% CI 0.92, 0.98) per 1 mg/1000 kcal in niacin intake. Higher intake of pyridoxine (HR 0.66; 95% CI 0.46, 0.96) and vitamin B12 (HR 0.87; 95% CI 0.77, 0.97) was associated with a decreased risk of IAA-first autoimmunity. Higher intake of riboflavin (HR 1.38; 95% CI 1.05, 1.80) was associated with an increased risk of GADA-first autoimmunity. There were no associations between any of the B vitamins and the outcomes "any IA" and progression from IA to T1D.  CONCLUSION: In this multinational, prospective birth cohort of children with genetic susceptibility to T1D, we observed some direct and inverse associations between different B vitamins and risk of IA.

The relationship between folate and diabetes remains inconclusive, possibly because of folate measured differentially between studies. Interference from mandatory folic acid fortification (FAF) has also been blamed. With both folate intake and circulating concentration measured, we assessed the relationship between folate and the risk of diabetes death in a hypertensive cohort established before FAF. We hypothesized that the association between folate and diabetes death is measurement dependent. We analyzed the data of 3133 hypertensive adults aged ≥19 years who participated in the Third National Health and Nutrition Examination Survey (1991-1994) and were followed up through December 31, 2010. Hazard ratios of diabetes death were estimated for participants with high (4th quarter) folate compared with those with moderate (2nd and 3rd quarters) or low (1st quarter) concentrations of folate. Dietary folate intake, total folate intake (including folate from supplements), serum, and red blood cell (RBC) folate were measured. After 42,025 person-years of follow-up, 165 diabetes deaths were recorded, and a dose-response positive association was observed between diabetes death and RBC folate. The adjusted hazard ratios of diabetes death were 1.00 (reference), 1.42 (95% CI. 1.20-1.68), and 2.21 (1.73-2.82), respectively, for hypertensive adults with low, moderate, and high RBC folate. No association was detected between diabetes death and serum folate concentration, folate intake, or either dietary intake or total intake. With minimized interference from FAF, neither dietary nor serum folate was associated with diabetes death, but elevated RBC folate was associated with a high risk of diabetes deaths among hypertensive patients.

Background & objectives Reducing maternal anaemia and enhancing feto-maternal health to achieve desired birth outcomes is a major health concern in India. Micronutrient deficiencies during pregnancy may impact fetal growth and neonatal outcomes. There is increasing interest in using multiple micronutrient supplement (MMS) during pregnancy. However, the World Health Organization (WHO) recommends use of MMS containing Iron and Folic Acid (IFA) in the context of "rigorous research". Against this backdrop, an Indian Council of Medical Research (ICMR)-led MMS design expert group met over six months to review the evidence and decide on the formulation of an India-specific MMS supplement for pregnant mothers for potential use in a research setting. Methods The India-MMS design expert group conducted a series of meetings to assess the available evidence regarding the prevalence of micronutrient deficiencies in pregnant women in India, the health benefits of supplementing with different micronutrients during pregnancy, as well as nutrient interactions within the MMS formulation. Based on these considerations, the expert group reached a consensus on the composition of the MMS tailored for pregnant women in India. Results The India-specific MMS formulation includes five minerals and 10 vitamins, similar to the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) composition. However, the quantities of all vitamins and minerals except Zinc, Vitamin E, and Vitamin B6 differ. Interpretation & conclusions This report provides an overview of the process adopted, the evidence evaluated, and the conclusions from the expert working group meetings to finalize an MMS supplement in pregnancy for the Indian context to be used in a research setting.

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.

The relationship between nutrition and brain health is intricate. Studies suggest that nutrients during early life impact not only human physiology but also mental health. Although the exact molecular mechanisms that depict this relationship remain unclear, there are indications that environmental factors such as eating, lifestyle habits, stress, and physical activity, influence our genes and modulate their function by epigenetic mechanisms to shape mental health outcomes. Epigenetic mechanisms act as crucial link between genes and environmental influences, proving that non-genetic factors could have enduring effects on the epigenome and influence health trajectories. We review studies that demonstrated an epigenetic mechanism of action of nutrition on mental health, focusing on the role of specific micronutrients during critical stages of brain development. The methyl-donor micronutrients of the one-carbon metabolism, such as choline, betaine, methionine, folic acid, VitB6 and VitB12 play critical roles in various physiological processes, including DNA and histone methylation. These micronutrients have been shown to alter gene function and susceptibility to diseases including mental health and metabolic disorders. Understanding how micronutrients influence metabolic genes in humans can lead to the implementation of early nutritional interventions to reduce the risk of developing metabolic and mental health disorders later in life.

Maternal body size, nutrition, and hyperglycemia contribute to neonatal body size and composition. There is little information on maternal-fetal transmission of messages which influence fetal growth. We analyzed adipocyte-derived small extracellular vesicular (ADsEV) microRNAs in maternal and cord blood to explore their adipogenic potential.

There were 279 mother-neonate pairs with all phenotypic data (normal glucose tolerant NGT = 148, gestational diabetes mellitus GDM = 131). Neonates with adiposity were those in the highest tertile (T3) of sex-specific sum of skinfolds and those without adiposity (lean) in the lowest tertile T1 of NGT pregnancies. We studied ADsEV miRNAs in 76 and 51 neonates with and without adiposity respectively and their mothers based on power calculations (68 NGT and 59 GDM pregnancies). ADsEV miRNAs from maternal and cord blood plasma samples were profiled on Agilent 8*60 K microarray. Differential expression (DE) of ADsEV miRNAs in adipose vs. lean groups was studied before and after adjustment for maternal GDM, adiposity, and vitamin B12-folate status.

Multiple miRNAs were common in maternal and cord blood and positively correlated. We identified 24 maternal and 5 cord blood miRNAs differentially expressed (discovery p ≤ 0.1) in the adipose group in unadjusted, and 19 and 26, respectively, in the adjusted analyses. Even though DE miRNAs were different in maternal and cord blood, they targeted similar adipogenic pathways (e.g., the forkhead box O (FOXO) family of transcription factors, mitogen‑activated protein kinase (MAPK) pathway, transforming growth factor beta (TGF-β) pathway). Maternal GDM and adiposity were associated with many DE ADsEV miRNAs.

Our results suggest that the ADsEV miRNAs in mothers are potential regulators of fetal adiposity. The expression and functionality of miRNAs appear to be influenced by maternal adiposity, hyperglycemia, and micronutrient status during pregnancy.

Growing evidence shows that maternal nutrition from preconception until lactation has an important effect on the development of non-communicable diseases in the offspring. Biological responses to environmental stress during pregnancy, including undernutrition or overnutrition of various nutrients, are transmitted in part by DNA methylation. The aim of the present narrative review is to summarize literature data on altered DNA methylation patterns caused by maternal macronutrient or vitamin intake and its association with offspring's phenotype (obesity and related metabolic changes). With our literature search, we found evidence for the association between alterations in DNA methylation pattern of different genes caused by maternal under- or overnutrition of several nutrients (protein, fructose, fat, vitamin D, methyl-group donor nutrients) during 3 critical periods of programming (preconception, pregnancy, lactation) and the development of obesity or related metabolic changes (glucose, insulin, lipid, leptin, adiponectin levels, blood pressure, non-alcoholic fatty liver disease) in offspring. The review highlights that maternal consumption of several nutrients could individually affect the development of offspring's obesity and related metabolic changes via alterations in DNA methylation.

Worldwide, diabetes mellitus represents a growing health problem. If it occurs during pregnancy, it can increase the risk of various abnormalities in early and advanced life stages of exposed individuals due to fetal programming occurring in utero. Studies have determined that maternal conditions interfere with the genotypes and phenotypes of offspring. Researchers are now uncovering the mechanisms by which epigenetic alterations caused by diabetes affect the expression of genes and, therefore, the development of various diseases. Among the numerous possible epigenetic changes in this regard, the most studied to date are DNA methylation and hydroxymethylation, as well as histone acetylation and methylation. This review article addresses critical findings in epigenetic studies involving diabetes mellitus, including variations reported in the expression of specific genes and their transgenerational effects.