Risk Of Obesity In Offspring Research Articles

RBM15 suppresses hepatic insulin sensitivity of offspring of gestational diabetes mellitus mice via m6A-mediated regulation of CLDN4

BackgroundGestational diabetes Mellitus (GDM) is a common pregnancy-specific disease with high morbidity, which is linked to a high risk of obesity and diabetes in offspring. N6-methyladenosine modification of RNA is emerging as an important epigenetic mechanism that is widely manifested in many diseases. This study aimed to investigate the mechanism of m6A methylation in metabolic syndrome in offspring result from intrauterine hyperglycemia.MethodsGDM mice were established by feeding a high-fat diet 1 weeks before pregnancy. The m6A RNA methylation quantification kit was used to detect liver tissue methylation levels. PCR array was used to determine the expression of the m6A methylation modification enzyme. Immunohistochemistry, qRT-PCR, and western blot were used to examine the expression of RBM15, METTL13, IGF2BP1, and IGF2BP2. Subsequently, methylated RNA immunoprecipitation sequencing combined with mRNA sequencing, followed by dot blot and glucose uptake tests, were performed.ResultsIn this study, we found that offspring from a GDM mother were more vulnerable to glucose intolerance and insulin resistance. GC–MS revealed significant metabolic changes including saturated fatty acids and unsaturated fatty acids in liver of GDM offspring. We also demonstrated that global mRNA m6A methylation level was significantly increased in the fetal liver of GDM mice, indicating epigenetic change may have a strong relationship with the mechanism of metabolism syndrome. Concordantly, RBM15, the RNA binding methyltransferase, was upregulated in the liver. In vitro, RBM15 suppressed insulin sensitivity and increased insulin resistance through m6A-regulated epigenetic inhabitation of CLDN4. Moreover, MeRIP-sequencing and mRNA-sequencing revealed that differently regulated genes with differential m6A peaks were enriched in metabolic pathways.ConclusionOur study revealed the essential role of RBM15 in insulin resistance and the effect of RBM15-regulated m6A modification in the metabolic syndrome of offspring of GDM mice.

Maternal pre-pregnancy body mass index is associated with newborn offspring hypothalamic mean diffusivity: a prospective dual-cohort study

BackgroundAn extensive body of animal literature supports the premise that maternal obesity during pregnancy can alter the development of the fetal hypothalamus (HTH, a critical regulator of energy balance) with implications for offspring obesity risk (i.e., long-term energy imbalance). Yet, the relationship in humans between maternal overweight/obesity during pregnancy and fetal hypothalamic development remains largely unknown. Here, using an international (Finland and California, USA) multi-site diffusion tensor imaging (DTI) dataset, we test the hypothesis that maternal pre-pregnancy BMI is associated with newborn offspring HTH mean diffusivity (HTH MD, a replicable neural correlate of BMI in adults).MethodsHTH MD was independently quantified in two separate BMI-matched cohorts (up to class II obesity; BMIRange = 17–35) using a high-resolution atlas-based definition of HTH. A total of n = 231 mother-child dyads were available for this analysis (nSite,1 = 152, age at MRI = 26.7 ± 8.1 days, gestational age at birth = 39.9 ± 1.2 weeks, nM/F = 82/70, BMI = 24.2 ± 3.8; nSite,2 = 79, age at MRI = 25.6 ± 12.5 days, gestational age at birth = 39.3 ± 1.5 weeks, nM/F = 45/34, BMI = 25.1 ± 4.0). The association between maternal pre-pregnancy BMI and newborn offspring HTH MD was examined separately in each cohort using linear regression adjusting for gestational age at birth, postnatal age at scan, sex, whole white matter mean diffusivity, and DTI quality control criteria. In post hoc analyses, additional potentially confounding factors including socioeconomic status, ethnicity, and obstetric risk were adjusted where appropriate.ResultsThe distribution of maternal pre-pregnancy BMI was comparable across sites but differed by ethnicity and socioeconomic status. A positive linear association between maternal pre-pregnancy BMI and newborn offspring HTH MD was observed at both sites (hat{beta}Site,1 = 0.17, pSite,1 = 0.01; hat{beta}Site,2 = 0.22, pSite,2 = 0.03) and remained significant after adjusting for cohort-relevant covariates.ConclusionsThese findings translate the preclinically established association between maternal obesity during pregnancy and offspring hypothalamic microstructure to the human context. In addition to further replication/generalization, future efforts to identify biological mediators of the association between maternal obesity and fetal HTH development are warranted to develop targeted strategies for the primary prevention of childhood obesity.

Maternal Polycystic Ovary Syndrome and the Risk of Early Childhood Obesity in Female Offspring: A Nationwide Population-Based Study.

To investigate the relationship between polycystic ovary syndrome (PCOS) in Korean women and childhood growth and obesity of their offspring. This longitudinal case-control study using the Korean National Health Insurance claims database and the National Health Screening Program for Infants and Children database included women who delivered singletons between January 2007 and December 2008. Offspring's body mass index (BMI) measurements taken between 42 and 80 months of age were compared according to a maternal history of PCOS. Among a total of 131,805 participants, 1,213 women had a history of PCOS and 130,592 women did not. Female offspring aged 66-80 months born to women with PCOS had significantly higher BMI than those born to women without PCOS; there was no significant difference in that of male offspring regardless of maternal PCOS. In the generalized estimating equation and multivariable logistic regression analyses, the female offspring born to women with PCOS had a significantly higher risk of obesity during the age of 42-54 and 66-80 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.09-2.21 and OR, 1.5; 95% CI, 1.05-2.15, respectively), than those born to women without PCOS, after adjusting for several confounding factors. Maternal PCOS is independently associated with an increased incidence of childhood obesity in female offspring among Korean women. Women with PCOS should consider the risk of early childhood obesity in their daughters, even if they maintain a healthy weight themselves.

Appetitive Motivation and Associated Neurobiology Change Differentially across the Life Course of Mouse Offspring Exposed to Peri- and Postnatal High Fat Feeding

Alterations in neural pathways that regulate appetitive motivation may contribute to increased obesity risk in offspring born to mothers fed a high fat (HF) diet. However, current findings on the impact of maternal obesity on motivation in offspring are inconclusive, and there is no information about the long-lasting effects in aged animals. This study examined the longitudinal effect of perinatal and chronic postnatal HF intake on appetitive motivation in young and aged offspring. Female C57Bl/6 were fed either a control (C) or HF diet before mating through to lactation. At weaning, offspring were maintained on the C or HF diet, generating the following four diet groups: C/C, C/HF, HF/C, and HF/HF based on the pre/post weaning diet. At 6 months, motivation was higher in HF/C females, but lower in male and female C/HF and HF/HF mice. By 12 months, this difference was lost, as C-fed animals became less motivated, while motivation increased in HF-fed mice. The mRNA levels of dopamine receptor 1 and 2 increased with age, while cannabinoid receptor 1 and μ-opioid receptor expression remained stable or decreased in mesolimbic and mesocortical dopaminergic pathways. Results from this study suggest that perinatal and chronic postnatal HF feeding produced opposite effects on appetitive motivation in young adult offspring mice, which was also reflected in the shift in motivation over time. These results have significant implications for patterns of hedonic eating across the life course and the relative risk of obesity at different time points.

A prospective birth cohort study of maternal prenatal cigarette smoking assessed by self-report and biomarkers on childhood risk of overweight or obesity.

Most studies on the association of in utero exposure to cigarette smoking and childhood overweight or obesity (OWO) were based on maternal self-reported smoking status, and few were based on objective biomarkers. The concordance of self-report smoking, and maternal and cord blood biomarkers of cigarette smoking as well as their effects on children's long-term risk of overweight and obesity are unclear. In this study, we analyzed data from 2351 mother-child pairs in the Boston Birth Cohort, a sample of US predominantly Black, indigenous, and people of color (BIPOC) that enrolled children at birth and followed prospectively up to age 18 years. In utero smoking exposure was measured by maternal self-report and by maternal and cord plasma biomarkers of smoking: cotinine and hydroxycotinine. We assessed the individual and joint associations of each smoking exposure measure and maternal OWO with childhood OWO using multinomial logistic regressions. We used nested logistic regressions to investigate the childhood OWO prediction performance when adding maternal and cord plasma biomarkers as input covariates on top of self-reported data. Our results demonstrated that in utero cigarette smoking exposure defined by self-report and by maternal or cord metabolites was consistently associated with increased risk of long-term child OWO. Children with cord hydroxycotinine in the fourth quartile (vs. first quartile) had 1.66 (95% confidence interval [CI] 1.03-2.66) times the odds for overweight and 1.57 (95% CI 1.05-2.36) times the odds for obesity. The combined effect of maternal OWO and smoking on offspring risk of obesity is 3.66 (95% CI 2.37-5.67) if using self-reported smoking. Adding maternal and cord plasma biomarker information to self-reported data improved the prediction accuracy of long-term child OWO risk. This longitudinal birth cohort study of US BIPOC underscored the role of maternal smoking as an obesogen for offspring OWO risk. Our findings call for public health intervention strategies to focus on maternal smoking - as a highly modifiable target, including smoking cessation and countermeasures (such as optimal nutrition) that may alleviate the increasing obesity burden in the United States and globally.

Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: results from three prospective cohort studies

ObjectiveTo assess whether maternal ultra-processed food intake during peripregnancy and during the child rearing period is associated with offspring risk of overweight or obesity during childhood and adolescence.DesignPopulation based prospective...

Association between maternal erythrocyte polyunsaturated fatty acid levels during pregnancy and offspring weight status: A birth cohort study.

BackgroundThe findings of the association between maternal polyunsaturated fatty acid (PUFA) levels during pregnancy and offspring weight status are controversial. Furthermore, few studies have focused on Asian populations or used erythrocyte membranes as biological markers. We aimed to examine the associations between maternal erythrocyte PUFA and offspring weight status within the first 2 years among the Chinese population.Materials and methodsA total of 607 mother-child pairs were recruited from a birth cohort. Maternal erythrocyte n-3 and n-6 PUFA during pregnancy were measured by gas chromatography, and the ratio of PUFA was calculated. Weight- and body mass index (BMI)-for-age z (WAZ and BAZ) scores were calculated for offspring at 1, 3, 6, 8, 12, 18, and 24 months of age. The risk of overweight and obesity was defined by the WHO criterion. The Generalized Estimating Equation (GEE) model was carried out for repeated anthropometric data within 2 years of age.ResultsMaternal erythrocyte docosapentaenoic acid (DPA, n-3) was inversely associated with offspring BAZ score [tertile 2 vs. tertile 1, β: −0.18 (−0.29, −0.00)]. Higher maternal erythrocyte arachidonic acid (AA) was inversely associated with lower offspring WAZ and BAZ [tertile 3 vs. tertile 1, β: −0.18 (−0.35, −0.02), −0.22 (−0.38, −0.06), respectively]. Furthermore, higher maternal erythrocyte AA [tertile 3 vs. tertile 1, odds ratio [OR]: 0.52 (0.36, 0.75), ptrend < 0.001] and total n-6 PUFA [tertile 3 vs. tertile 1, OR: 0.56 (0.39, 0.81), ptrend = 0.002] were associated with decreased risk of overweight and obesity in offspring. Maternal erythrocyte n-6/n-3 PUFA and AA/eicosapentaenoic acid (EPA) ratios were not associated with offspring weight status.ConclusionMaternal erythrocyte PUFA might influence offspring weight status within 2 years of age in the Chinese population. Further Asian studies are still needed.

Growth patterns among late preterm infants of mothers with diabetes

Objective Exposure to diabetes mellitus during pregnancy increases the risk of offspring obesity and cardiometabolic disease. Limited information exists regarding growth patterns among preterm infants exposed to maternal diabetes. This study describes growth differences during early childhood among late preterm infants of mothers with and without diabetes during pregnancy. Materials and methods In a retrospective longitudinal analysis, weight trajectories from birth to age 2 years were compared between diabetes exposure groups (N = 1554) using mixed effects modeling and adjusting for maternal and infant demographic covariates. Results Overall, 134 (9%) infants were exposed to diabetes (DM-group). DM-group had higher average weight (adjusted difference 300 g [95% CI: 228, 371]) and weight z-score (adjusted difference 0.67 standard deviation scores (SDS) [95% CI: 0.50, 0.84]) compared with unexposed infants. DM-group infants had accelerated weight gain from birth to discharge (adjusted weight difference 31.8 g [95% CI: 12.5, 51.1], adjusted weight z-score difference 0.07 SDS [95% CI: 0.02, 0.11]) compared with unexposed infants, including in the first postnatal week (adjusted weight gain velocity difference, day 0–3: 6.07 g/day [95% CI: 0.88, 11.25]; day 3–7: 8.37 g/day [95% CI: 1.60, 15.13]). Through age two, infants in the DM-group maintained higher average weight (adjusted difference 185.7 g [95% CI: 37.2, 334.3]) and weight z-score (adjusted difference 0.32 SDS [95% CI: 0.09, 0.55]) than unexposed infants, with greater weight gain between 18 and 24 months (adjusted difference 28.5 g/week [95% CI: 2.6, 54.4]). Conclusions Maternal diabetes exposed late preterm infants had higher weight from birth to age two and greater weight gain in the first postnatal week than unexposed infants. Long term risk associated with weight trajectories in this population requires further study.

Lactation duration affects obesity risk in rat offspring.

Lactation duration affects obesity risk in rat offspring.

1420-P: Gestational Diabetes Glyburide Treatment and Glycemic Control: Associations with Risk of Subsequent Child Obesity

Gestational diabetes mellitus (GDM) increases offspring obesity risk. GDM severity, treatment, glycemic control and postnatal feeding behaviors increase or alleviate child obesity risk. This study sought to evaluate GDM treatment (glyburide vs. diet) and glycemic control related to overweight/obesity risk in toddlers of mothers with GDM. In a diverse prospective cohort of 786 GDM mother-child dyads (78% minority: Hispanic, Asian, Black and 22% White) , we measured prenatal glycemic control (daily home testing) , GDM severity, treatment, postnatal diet, and child BMI at age 2-5 y. Maternal glycemia was categorized as optimal control (≥80% of fasting &amp; post-prandial blood glucose tests met target) or not optimal control (&amp;lt;80%) . Child weight and height was categorized by BMI percentiles (age, sex) ; normal weight (&amp;lt;85th) , overweight (85-95th) or obese (&amp;gt;95th) . Multinomial logistic regression estimated odds ratios (OR) 95%CI of overweight and obesity associated with treatment and glycemic control adjusted for prenatal, newborn and postnatal covariates. On average, mothers were 33.3 (SD 4.7) y at delivery with prepregnancy BMI 29.3 (7.1) kg/m2 and 74% had optimal glycemic control. Children were age 40.5 (6.3) months at BMI measurement; 76% normal weight, 13% overweight and 11% obese. Glyburide was associated with higher risk of obesity, 1.75 (1.05-2.91) independent of glycemic control. Stratifying by glycemic control, glyburide was associated with borderline higher odds of obesity (2.79, 0.94-8.33, p=0.065) among those not in optimal control adjusted for GDM severity, pre-pregnancy BMI, sociodemographic, newborn size and infant diet. Longer breastfeeding was associated with lower odds of obesity (0.83, 0.75-0.93) and sugary drink or fruit juice intake birth to 1 y was associated with higher odds of obesity (4.14, 1.06-16.19) . Glyburide treatment of GDM and sugary infant diet may contribute to obesity in young children if maternal glycemic control was not optimal. Disclosure J.L.Josefson: n/a. E.P.Gunderson: None. B.Sun: None. M.Greenberg: None. L.Greenspan: None. J.N.Davis: None. B.E.Metzger: None. J.C.Lo: None. M.S.Faith: None. W.Lowe: None. Funding National Institutes of HealthRDK122700

Relationship between parental reproductive age and the risk of overweight and obesity in offspring

Objective: To explore the role of parental reproductive age on the risk of overweight and obesity in offspring. Methods: The participants were derived from physical examination data of students aged 6-18 years in seven provinces in China, and questionnaire survey was used to collect demographic characteristics and lifestyle information of the students and their parents. A total of 41 567 children with complete data were included. According to the restricted cubic spline curve, maternal reproductive age was divided into three categories, 14-23, 24-28, and 29-38 years, and paternal reproductive age was divided into 14-23, 24-30, and 31-42 years. Multivariate logistic regression model was used to analyze the association between parental reproductive age and parental nutritional status and the risk of overweight and obesity in offspring. Results: The mean age of 41 567 children was (10.6±3.2) years, and the mean paternal and maternal age were (27.9±4.4) years and (25.8±4.0) years, respectively. The detection rate of overweight and obesity was 23.4%. After adjusting factors of children diet and behaviors, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 24-28 years was 1.11 (1.04-1.18) and 1.16 (1.08-1.24), respectively. When none parents were overweight and obese, the difference of obesity risk was not statistically significant. When both parents were overweight and obese, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 14-28 years old was 1.27 (1.00-1.62) and 1.33 (1.07-1.65) respectively. Conclusion: Parental reproductive age and parental overweight and obesity status may both increase the risk of overweight and obesity in offspring, with a significant interaction effect.

Associations of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain with Offspring Obesity Risk.

Gestational diabetes mellitus (GDM) and gestational weight gain (GWG) are important risk factors that are known to affect offspring growth, but these outcomes are inconsistent and it remains unknown if both risk factors have a synergetic effect on early childhood growth. The present study aimed to conduct offspring body mass index-for-age Z-scores (BMIZ) trajectories and to evaluate the independent and interactive effect of the status of GDM and excessive GWG on the risks of overweight/obesity from birth to 24 months of age. A total of 7949 mother-child pairs were enrolled in this study. The weight and length of children were measured at birth, 6, 12, and 24 months of age to calculate BMIZ. The status of GDM was positively associated with offspring BMIZ and risk of macrosomia at birth but was not associated with offspring BMIZ or the risks of overweight/obesity at 6, 12, and 24 months of age. In contrast, excessive GWG was positively linked to offspring BMIZ, the stable high BMIZ trajectory pattern, and risks of overweight/obesity in the first 24 months of age. These two risk factors also had a significant synergistic effect on macrosomia at birth, but the interactive effect was only significant in boys during the follow-up years in the sex-stratified analyses. The maternal GWG was a more pronounced predictor than GDM with relation to BMIZ and risk of overweight/obesity in early childhood. The interactive effect between these risk factors on offspring overweight/obesity may vary by sex.

Prenatal Education Intervention for Increasing Knowledge and Changing Attitude Toward Offspring Obesity Risk Factors.

This pre- and post-test quasi-experimental design study pilot tested an educational intervention designed to increase knowledge of and change attitudes toward prenatal factors that increase risk of childhood offspring obesity in 36 pregnant women. Educational intervention content included monitoring blood glucose, gestational weight gain in pregnancy, healthy lifestyle choices, and breastfeeding. Education intervention delivery method included: Verbal, written, and video. Participants' knowledge improved after the intervention for most topics (p = .03-.000). Their attitude score also differed before and after intervention (p = .002). Video delivery mode was the most useful, attractive, and most helpful method. This study showed an education intervention could potentially increase pregnant women's knowledge and attitudes toward offspring obesity risk factors.

Body mass index in the middle-aged offspring of parents with severe mental illness.

People with severe mental illness (SMI) have an elevated risk of obesity but the causes and mechanisms are unclear. We explored the familial association between parental SMI and body mass index (BMI) in middle-aged offspring. Our objective was to determine if the offspring of either parent with SMI have an increased risk for obesity. The Northern Finland Birth Cohort 1966 is a cohort study of offspring with expected date of birth in 1966. The data include originally 12 068 mothers and 12 231 children from the provinces of Lapland and Oulu in Finland. The final study sample included 5050 middle-aged offspring. Parental SMI was used as exposure in the study. BMI measured at the age of 46 years was used as a primary outcome. Risk for obesity was elevated in the offspring of mothers with SMI [overweight: adjusted odds ratio (OR) 1.93 (1.29-2.90), obese class I: 1.97 (1.20-3.25), obese classes II-III: 2.98 (1.67-5.33)]. For the offspring of either parent with SMI, statistically significant results were found in obese class I and obese classes II-III [overweight: adjusted OR 1.21 (0.94-1.54), obese class I: 1.52 (1.03-1.08), obese classes II-III: 1.53 (1.01-2.32)]. We found an elevated risk of obesity in the middle-aged offspring of either parent with SMI, especially in the offspring of mothers with SMI. Thus, there might be a common familial pathway leading to the co-occurrence of obesity and SMI.

A high-protein low–glycemic index diet attenuates gestational weight gain in pregnant women with obesity: the “An optimized programming of healthy children” (APPROACH) randomized controlled trial

Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity. We aimed to investigate the effect of a high-protein low-glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity. A total of 279 women with prepregnancy overweight or obesity (BMI: 28-45kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high-protein low-glycemic index diet (HPLGI: 25%-28% of energy from protein and glycemic index≤55) and a moderate-protein moderate-glycemic index diet (MPMGI: 15%-18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence. Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8±1.3kg among women assigned the HPLGI diet and this was significantly lower, by -1.7kg (95% CI: -2.8, -0.5kg; P = 0.004), than the GWG of 8.5±1.3kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birth weight and other anthropometric measures). The incidence of composite pregnancy complications was lower for the HPLGI than for the MPMGI diet (35.4% compared with 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%-2%) did not differ between groups. A moderate increase in dietary protein in conjunction with a reduction in glycemic index during the last 2 trimesters of pregnancy reduced GWG and limited complications and cesarean deliveries among women with overweight or obesity.

A Metagenomics Investigation of Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome.

To identify possible mechanisms by which maternal consumption of non-nutritive sweeteners increases obesity risk in offspring, we reconstructed the major alterations in the cecal microbiome of 3-week-old offspring of obese dams consuming high fat/sucrose (HFS) diet with or without aspartame (5–7 mg/kg/day) or stevia (2–3 mg/kg/day) by shotgun metagenomic sequencing (n = 36). High throughput 16S rRNA gene sequencing (n = 105) was performed for dams, 3- and 18-week-old offspring. Maternal consumption of sweeteners altered cecal microbial composition and metabolism of propionate/lactate in their offspring. Offspring daily body weight gain, liver weight and body fat were positively correlated to the relative abundance of key microbes and enzymes involved in succinate/propionate production while negatively correlated to that of lactose degradation and lactate production. The altered propionate/lactate production in the cecum of weanlings from aspartame and stevia consuming dams implicates an altered ratio of dietary carbohydrate digestion, mainly lactose, in the small intestine vs. microbial fermentation in the large intestine. The reconstructed microbiome alterations could explain increased offspring body weight and body fat. This study demonstrates that intense sweet tastants have a lasting and intergenerational effect on gut microbiota, microbial metabolites and host health.

Cardiometabolic Disorders in the Offspring of Parents With Severe Mental Illness.

The elevated prevalence of cardiometabolic disorders is consistently reported in patients with severe mental illness (SMI). We explored the association between parental SMI and offspring cardiometabolic morbidity. Our hypothesis was that offspring of people with SMI have increased morbidity risk. The Northern Finland Birth Cohort 1966 is a study of offspring whose date of birth was expected in 1966. The follow-up lasted until 2015 (49 years). The final study sample included 11,175 children. We used parental SMI as the exposure in the study. The following cardiometabolic disorders were used as outcome measures: diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease, obesity, and cerebrovascular disorders. There were 139 (14.7%; hazard ratios [HR] = 1.63; 95% confidence interval [CI] = 1.36-1.94) children of parents with SMI who developed cardiometabolic disorder during follow-up and 957 (9.4%) in the comparison cohort. Statistically significant HRs were found in males (HR = 1.95; 95% CI =1.56-2.44), but not in females (HR = 1.29; 95% CI = 0.96-1.73). Having a cardiometabolic disorder was associated with male offspring of parents with SMI. Our findings suggest that there is an elevated risk of coronary artery disease, hyperlipidemia, obesity, and hypertension in the male offspring of parents with SMI. Our results suggest that the somatic health of offspring of parents with SMI should also be considered in addition to their mental health in clinical practice.

Maternal Obesity Related to High Fat Diet Induces Placenta Remodeling and Gut Microbiome Shaping That Are Responsible for Fetal Liver Lipid Dysmetabolism.

Background: Maternal obesity in utero may affect fetal development and cause metabolic problems during childhood and even adulthood. Diet-induced maternal obesity can impair gut barrier integrity and change the gut microbiome, which may contribute to adverse placental adaptations and increase the obesity risk in offspring. However, the mechanism through which maternal obesity causes offspring metabolic disorder must be identified.Methods: Eight-week-old female rats received a control diet or high-fat (HF) diet for 11 weeks before conception and during gestation. The placentas were collected on gestational day 21 before offspring delivery. Placental tissues, gut microbiome, and short-chain fatty acids of dams and fetal liver tissues were studied.Results: Maternal HF diet and obesity altered the placental structure and metabolism-related transcriptome and decreased G protein–coupled receptor 43 expression. HF diet and obesity also changed the gut microbiome composition and serum propionate level of dams. The fetal liver exhibited steatosis, enhanced oxidative stress, and increased expression of acetyl-CoA carboxylase 1 and lipoprotein lipase with changes in maternal HF diet and obesity.Conclusions: Maternal HF diet and obesity shape gut microbiota and remodel the placenta of dams, resulting in lipid dysmetabolism of the fetal liver, which may ultimately contribute to the programming of offspring obesity.

The impact of parity and maternal obesity on the fetal outcomes of a non-selected Lower Saxony population.

Maternal obesity during pregnancy is associated with adverse intrauterine events and fetal outcomes and may increase the risk of obesity and metabolic disease development in offspring. Higher parity, regardless of socioeconomic status, is associated with increased maternal body mass index (BMI). In this study, we examined the relationship between parity, maternal obesity, and fetal outcomes in a large sample of mother-neonate pairs from Lower Saxony, Germany. This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony's statewide quality assurance initiative. 448,963 cases were included. Newborn outcomes were assessed in relation to maternal BMI and parity. Maternal obesity was associated with an increased risk of placental insufficiency, chorioamnionitis, and fetal distress while giving birth. This effect was present across all parity groups. Fetal presentation did not differ between BMI groups, except for the increased risk of high longitudinal position and shoulder dystocia in obese women. Maternal obesity was also associated with an increased risk of premature birth, low arterial cord blood pH and low 5-min APGAR scores. Maternal obesity increases the risk of adverse neonatal outcomes. There is a positive correlation between parity and increased maternal BMI. Weight-dependent fetal risk factors increase with parity, while parity-dependent outcomes occur less frequently in multipara. Prevention and intervention programs for women planning to become pregnant can be promising measures to reduce pregnancy and birth complications.

Metformin for pregnancy and beyond: the pros and cons.

Metformin has been used in pregnancy since the 1970s. It is cheap, widely available and is acceptable to women. Despite its increasing use, controversy remains surrounding its benefits and risks. Metformin effectively reduces hyperglycaemia for the mother during pregnancy and it reduces rates of macrosomia and neonatal hypoglycaemia. However, concern exists surrounding an increase in the rate of SGA births and obesity in childhood. We aim to review the evidence and expert opinion behind metformin in pregnancy through to the post-partum period. We performed a literature review of relevant studies from online databases using a combination of keywords. We also searched the references of retrieved articles for pertinent studies. There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations. If used throughout pregnancy, it is likely to lead to reduced maternal weight gain and reduced insulin dose in women with type 2 diabetes. In infants, metformin reduces hypoglycaemia and macrosomia but may increase the rate of infants born SGA. There is some evidence of an increased risk of obesity and altered fat distribution in offspring. Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy. Due to increasing rates of maternal obesity, GDM and type 2 diabetes, metformin use in pregnancy is increasing. Overall, it appears safe and effective but further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies.