Maternal Metabolic Status Research Articles

Omega-3 reverses the metabolic and epigenetically regulated placental phenotype acquired from preconceptional and peri-conceptional exposure to air pollutants

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

Gestational exposure to air pollutants perturbs metabolic and placenta-fetal phenotype

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

Effects of dam metabolic profile and seasonality (Spring vs. Winter) on their offspring' metabolism, health, and immunity: maternal factors in dairy calves' analytes.

Maternal status during the transition period can significantly impact the health and performance of Holstein dairy calves, with lasting effects on various variables. However, the relationship between maternal late gestation metabolic status, seasonality, and their impact on offspring remains unclear. This study aimed to assess the influence of maternal variables at calving on the performance, metabolism, and immunity of 28 dairy calves during their first month of life. Blood samples were collected from 28 Holstein cows at calving. Median results for maternal variables including non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), glucose, total protein (TP), albumin, triglycerides (TG), total cholesterol (TC), haptoglobin (Hp), body weight (BW), and body condition score (BCS) were determined. These median values served as a basis for categorizing the offspring into two groups based on their dams' high or low degree of each maternal variable. Additionally, calves were categorized by the season of birth (Spring vs. Winter), with 14 in each. Blood samples were collected from the calves at birth and on days 1, 7, 14, and 28 to assess IgG, biochemical parameters, and haptoglobin concentration. Reactive oxygen species (ROS) production by polymorphonuclear cells stimulated by various agents was also evaluated. Clinical assessments were conducted for diarrhea and bovine respiratory disease frequencies. Despite the overall health of the cows, differences were observed in the calves between maternal groups. Heavier cows with high maternal BCS tended to have larger offspring, while high maternal BCS was associated with increased diarrhea prevalence. Low maternal BCS resulted in a stronger innate immune response, indicated by higher ROS production. Calves from cows experiencing metabolic changes during calving displayed elevated Hp concentrations. Spring-born calves were larger but had lower serum IgG concentration and reduced innate immune response compared to winter-born calves. Additionally, spring-born calves exhibited higher Hp and increased diarrhea prevalence on day 28. These findings underscore the importance of the prenatal period in determining neonatal health and suggest further research to elucidate the long-term clinical implications of maternal effects on offspring health and growth. Investigating offspring constituents later in life can provide insight into the persistence of maternal effects over time.

Effects of improved on-farm crop storage on DNA methylation of mothers and their infants: evidence from a randomized controlled trial in Kenya

BackgroundStress during pregnancy can lead to adverse maternal and infant health outcomes through epigenetic changes in the hypothalamic–pituitary–adrenal axis. Among farmers in low-income countries, one important stressor is food insecurity, which can be reduced using hermetic storage bags. This study aimed to determine, for the first time, whether a hermetic storage bag intervention during pregnancy positively affects maternal and infant DNA methylation of the hypothalamic–pituitary–adrenal axis-related genes FKBP5 and NR3C1. We further analyzed whether anthropometrics, stress, and mental health were associated with DNA methylation.MethodsThis study was part of a larger matched-pair randomized controlled trial focusing on the impact of improved on-farm storage on food security, poverty, and net income of smallholder farming households. A total of N = 149 mothers were recruited by telephone and invited to attend a study appointment at health facilities in Kakamega County, Western Kenya, with their infants in April or May 2021. During the appointment, anthropometric measurements were taken, questionnaires on stress and mental health were administered, and saliva samples were collected. Logistic and multiple linear regression were used to examine the effect of the intervention and related measures on DNA methylation.ResultsMothers in the intervention group showed higher mean NR3C1 methylation levels than those in the control group, corrected for multiple testing. Maternal postpartum body mass index was positively associated with infant NR3C1 CpG3 DNA methylation. The more stressful life events a mother had experienced in the previous 12 months (including during pregnancy), the lower her FKBP5 CpG3 methylation levels.ConclusionsFood insecurity and stressful life events during pregnancy seem to exert significant effects on maternal DNA methylation. While these stressors did not appear to impact infant DNA methylation in the present study, maternal postpartum body mass index was significantly related to infant methylation. These findings suggest that while infants may be protected from excessive maternal glucocorticoids by placental barrier activity, maternal metabolic status is still reflected in their epigenetic make-up.Trial registration This study was part of a larger matched-pair randomized controlled trial on the impact of improved on-farm crop storage on welfare, nutrition, and human health. Registration can be found in the American Economic Association (AEA) RCT Registry, RCT ID: AEARCTR-0005845.

Metformin exposure during pregnancy and lactation affects offspring's long-term body weight and adipose tissue mass independent of the maternal metabolic state

The increasing prevalence of obesity, type 2 diabetes mellitus (T2DM), and gestational diabetes (GDM) among pregnant women has risen dramatically worldwide. The antihyperglycemic drug metformin is the most common drug for T2DM treatment in non-pregnant individuals; nevertheless, it is increasingly being used for diabetes-complicated pregnancies. Studies on the long-term metabolic effects of this drug in offspring remain scarce. This work aimed to determine the effect of metformin exposure during pregnancy and lactation on the offspring of a model of diet-induced maternal hyperglycemia.Cohorts of pregnant mice were fed a 46% fat diet (HFD) or a control standard diet (SD). A group of dams were exposed to metformin during pregnancy and lactation. After weaning, the offspring were fed SD for 8 weeks and then challenged with a 46% HFD after puberty for 12 weeks. Irrespective of the maternal diet, offspring of metformin-exposed mothers had a lower body weight and reduced inguinal white adipose tissue (iWAT) mass after HFD challenge. This was associated with increased expression of Pparg, Fabp4, Glut4, Srebp1, and Fasn in the iWAT during adulthood in the metabolically impaired dams exposed to metformin, suggesting increased adipogenesis and de novo lipogenesis. Increased expression of Fasn associated with decreased methylation levels at its promoter and proximal coding region in the iWAT was found. These results suggest that metformin modulates gene expression levels by epigenetic mechanisms in maternal metabolic-impaired conditions.

Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment.

Pregnancy complicated by obesity represents an increased risk of unfavorable perinatal outcomes such as gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, preterm birth, and impaired fetal growth, among others. Obesity is associated with deficiencies of micronutrients, and pregnant women with obesity may have higher needs. The intrauterine environment in pregnancies complicated with obesity is characterized by inflammation and oxidative stress, where maternal nutrition and metabolic status have significant influence and are critical in maternal health and in fetal programming of health in the offspring later in life. Comprehensive lifestyle interventions, including intensive nutrition care, are associated with a lower risk of adverse perinatal outcomes. Routine supplementation during pregnancy includes folic acid and iron; other nutrient supplementation is recommended for high-risk women or women in low-middle income countries. This study is an open label randomized clinical trial of parallel groups (UMIN Clinical Trials Registry: UMIN000052753, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000060194) to evaluate the effect of an intensive nutrition therapy and nutrient supplementation intervention (folic acid, iron, vitamin D, omega 3 fatty acids, myo-inositol and micronutrients) in pregnant women with obesity on the prevention of GDM, other perinatal outcomes, maternal and newborn nutritional status, and infant growth, adiposity, and neurodevelopment compared to usual care. Given the absence of established nutritional guidelines for managing obesity during pregnancy, there is a pressing need to develop and implement new nutritional programs to enhance perinatal outcomes.

Maternal Metabolic Status and Orofacial Cleft Risk: A Case-Control Study in Thailand

ObjectivesMetabolic syndrome (MetS) has been suggested to play a role in congenital defects. This study investigated the association of MetS and its components with orofacial clefts (OFCs). MethodsWe conducted a case-control study in Northeast Thailand. Ninety-four cases with cleft lip, with or without cleft palate, were frequency matched with 94 controls on the infant's age and mother's education. We administered a mother's health questionnaire and collected anthropometric measurements and blood samples. Multiple logistic regression was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed among infants without a family history of OFCs, mothers who were not currently breastfeeding, and mothers who were >6 months postpartum. ResultsWhen compared to mothers of normal weight, the OR associated with OFCs were 2.44 (95% CI, 1.04–5.76, p=0.04) in overweight mothers, and 3.30 (95% CI, 1.14–9.57, p=0.03) in obese mothers. Low HDL-C raised the risk of OFCs 2.95 times (95% CI, 1.41–6.14, p=0.004) compared to normal HDL-C levels. Mothers with 4 or 5 features of MetS were 2.77 times as likely to have the affected child than those who did not (95%CI, 0.43–17.76), but this difference was not statistically significant (p=0.28). Subgroup analyses showed similar results, uncovering an additional significant association between underweight mothers and OFCs. ConclusionsThe results indicate a robust association between underweight and overweight/obese maternal body mass index and increased OFC risk. Additionally, low HDL-C in mothers is linked to an elevated risk of OFCs. Further research is needed to evaluate if promoting strategies to maintain optimal body weight and enhance HDL-C levels in reproductive-age and pregnant women can contribute to reducing the risk of OFCs.

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring.

Gestational diabetes mellitus (GDM) is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development. As a bridge between the mother and the fetus, the placenta has nutrient transport functions, endocrine functions, etc., and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status. Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus. There are many reports on the placental pathophysiological changes associated with GDM, the impacts of GDM on the growth and development of offspring, and the prevalence of GDM in offspring after birth. Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases. This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

Sweet Spot Regulation of Maternal Metabolic Health and Nutrition on β-Cell Mass in the Offspring.

Maternal nutrition and metabolic health status during pregnancy are critical factors that shape the life-long health trajectory of offspring. Altered nutrition during specific times of development in utero can lead to functional changes in tissues such as the pancreatic β-cells, predisposing those tissues to metabolic diseases and Type 2 diabetes that manifest later in life. This chapter will focus on the role of pregnancy complications with altered nutrition during gestation in the maladaptive programming of β-cell mass and function in the offspring.

Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice

ObjectiveThe incidence of gestational diabetes mellitus (GDM) and metabolic disorders during pregnancy are increasing globally. This has resulted in increased use of therapeutic interventions such as metformin to aid in glycemic control during pregnancy. Even though metformin can cross the placental barrier, its impact on offspring brain development remains poorly understood. As metformin promotes AMPK signaling, which plays a key role in axonal growth during development, we hypothesized that it may have an impact on hypothalamic signaling and the formation of neuronal projections in the hypothalamus, the key regulator of energy homeostasis. We further hypothesized that this is dependent on the metabolic and nutritional status of the mother at the time of metformin intervention. Using mouse models of maternal overnutrition, we aimed to assess the effects of metformin exposure on offspring physiology and hypothalamic neuronal circuits during key periods of development. MethodsFemale C57BL/6N mice received either a control diet or a high-fat diet (HFD) during pregnancy and lactation periods. A subset of dams was fed a HFD exclusively during the lactation. Anti-diabetic treatments were given during the first postnatal weeks. Body weights of male and female offspring were monitored daily until weaning. Circulating metabolic factors and molecular changes in the hypothalamus were assessed at postnatal day 16 using ELISA and Western Blot, respectively. Hypothalamic innervation was assessed by immunostaining at postnatal days 16 and 21. ResultsWe identified alterations in weight gain and circulating hormones in male and female offspring induced by anti-diabetic treatment during the early postnatal period, which were critically dependent on the maternal metabolic state. Furthermore, hypothalamic agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neuronal innervation outcomes in response to anti-diabetic treatment were also modulated by maternal metabolic state. We also identified sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure. ConclusionWe demonstrate a unique interaction between anti-diabetic treatment and maternal metabolic state, resulting in sex-specific effects on offspring brain development and physiological outcomes. Overall, based on our findings, no positive effect of metformin intervention was observed in the offspring, despite ameliorating effects on maternal metabolic outcomes. In fact, the metabolic state of the mother drives the most dramatic differences in offspring physiology and metformin had no rescuing effect. Our results therefore highlight the need for a deeper understanding of how maternal metabolic state (excessive weight gain versus stable weight during GDM treatment) affects the developing offspring. Further, these results emphasize that the interventions to treat alterations in maternal metabolism during pregnancy need to be reassessed from the perspective of the offspring physiology.

Impact of maternal cardiometabolic status after bariatric surgery on the association between telomere length and adiposity in offspring

The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother’s metabolic status on children’s telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = − 0.80, p < 0.001) and significant differences were observed on age-adjusted DNAmTL between children born before versus after the maternal bariatric surgery. The associations found between body mass index and body fat percentage with DNAmTL in children born after the surgery were influenced by maternal triglycerides, TG/HDL-C ratio and TyG index. This study reports the impact of maternal bariatric surgery on offspring telomere length. The influence of maternal metabolic status on the association between telomere length and markers of adiposity in children suggests a putative modulating effect of bariatric surgery on the cardiometabolic risk in offspring.

The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.

Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear. We recruited exclusively breastfeeding mothers from among the donors of the human milk bank established at National Cheng-Kung University Hospital. The donor mothers provided 35 BM samples at three months (3M; before introducing children to complementary feeding) and 23 BM samples at six months (6M; after introducing children to complementary feeding) postpartum. At both time points, samples from different body sites, including nasal swabs, oral swabs and stool, were collected from the mothers and their infants. Maternal BMI was inversely associated with coagulase-negative Staphylococcus (CoNS) abundance in breastmilk. Staphylococcus caprae representation in BM CoNS showed a negative correlation with Streptococcus abundance. Network analysis revealed that infants fed Staphylococcus-dominated BM had better gut and nasal microbiota networks than infants fed Streptococcus-abundant BM during early infancy. Our work suggests that maternal metabolic status plays a crucial role in Staphylococcus/Streptococcus competition in BM, which in turn can impact the development of the infant microbiota. Our microbiota co-occurrence network analysis might serve as a helpful bioinformatic tool to monitor microbiota maturation during early infancy.

Maternal metabolic status and in-vitro culture conditions during embryonic genome activation deregulate the expression of energy-related genes in the bovine 16-cells embryo.

The molecular consequences of the metabolic stress caused by milk production of dairy cows in the early embryo are largely unknown. The objective was to determine the impact of dam metabolic status or in vitro culture during embryonic genome activation (EGA) on the transcriptomic profiles of bovine 16-cell stage embryos. Two days after synchronized oestrus, in vitro produced 2- to 4-cell stage embryos were endoscopically transferred in pools of 50 into the oviduct ipsilateral to the corpus luteum of lactating (LACT, n = 3) or nonlactating (i.e. dried off immediately at calving; DRY, n = 3) dairy cows. On Day 4, the oviducts were flushed to recover the embryos. Pools of five Day-2 embryos (n = 5) and Day-4 16-cell stage embryos obtained in vitro (n = 3) or from LACT or DRY cows were subjected to RNAseq. Temporally differentially expressed genes (DEG; FDR<0.05) between Day-2 and Day-4 embryos were determined considering the differences between the three conditions under which EGA occurred. Also, DEG between Day-4 embryos derived from the three conditions were identified. Functional analysis of the temporal DEG demonstrated that genes involved in ribosome, translation and oxidative phosphorylation in the mitochondria were strongly more expressed in Day-4 than Day-2 embryos. Comparison of Day-4 embryos that underwent EGA in vitro, or in LACT or DRY cows, identified DEG enriching for mitochondrial respiration and protein translation, including the mTOR pathway. In conclusion, exposure of the embryo to an unfavourable maternal metabolic status during EGA influences its transcriptome and potentially the competence for pregnancy establishment.

Bioactive peptides in preterm human milk: Impact of maternal characteristics and their association to neonatal outcomes.

Human milk adipokines in term babies seem partially determined by maternal factors and affect infant's development. We aimed to describe bioactive peptide concentration in very preterm human milk and associations to maternal characteristics and postnatal growth. Mothers delivering ≤32 weeks of gestation and their infant/s were recruited. At 4 weeks of lactation, an aliquot of 24-h-pooled milk was collected for exclusively breastfeeding dyads. Insulin, leptin, adiponectin, and milk fat globule epidermal growth factor-8 (MFG-E8) were measured by enzyme-linked immunoabsorbent assay in skimmed milk. One hundred mothers (28.8 ± 2.3 weeks at delivery) provided a milk sample. Milk insulin was related to gestational age, pre-pregnancy body mass index (BMI), and galactagogue treatment (final model: adjusted R2 : 0.330, p < 0.0001; adjusted β coefficients: galactagogue treatment: 0.348, p 0.001; pre-pregnancy BMI: 0.274, p 0.009; gestational age: -0.290, p 0.007). Adiponectin was higher in mothers with gestational diabetes (30.7 ± 6.5 vs. 24.8 ± 8 ng/mL, p 0.044). Leptin was associated with pre-pregnancy BMI (Spearman's ρ: 0.648, p < 0.0001) and MFG-E8 to presence of labor and multiple pregnancy (final linear regression model, R2 : 0.073, p 0.028, adjusted β coefficients: presence of labor -0.229, p 0.050; twins: -0.192, p 0.099). Milk adiponectin was associated with a greater decrease in length z-scores from birth to 28 days (Pearson's r: -0.225, p 0.032) and to discharge (Pearson's r: -0.290, p 0.003). Milk MFG-E8 was lower in milk of mothers whose babies experienced late-onset sepsis (13.3 ± 5.8 vs. 16.8 ± 6.3 μg/mL, p 0.023). Adipokines levels in preterm human milk are partially related to maternal metabolic status. Milk peptide concentration associates with early neonatal growth trajectories.

Exercise intervention during pregnancy induces DNA methylation alterations in maternal blood and cord blood.

Exercise intervention during pregnancy induces DNA methylation alterations in maternal blood and cord blood.

Metabolic effects of early life stress and pre-pregnancy obesity are long-lasting and sex-specific in mice.

Early life stress (ELS) is associated with metabolic-, cognitive-, and psychiatric diseases and has a very high prevalence, highlighting the urgent need for a better understanding of the versatile physiological changes and identification of predictive biomarkers. In addition to programming the hypothalamic-pituitary-axis (HPA), ELS may also affect the gut microbiota and metabolome, opening up a promising research direction for identifying early biomarkers of ELS-induced (mal)adaptation. Other factors affecting these parameters include maternal metabolic status and diet, with maternal obesity shown to predispose offspring to later metabolic disease. The aim of the present study was to investigate the long-term effects of ELS and maternal obesity on the metabolic- and stress phenotype of rodent offspring. To this end, offspring of both sexes were subjected to an adverse early-life experience, and their metabolic and stress phenotypes were examined. In addition, we assessed whether a prenatal maternal and an adult high-fat diet (HFD) stressor further shape observed ELS-induced phenotypes. We show that ELS has long-term effects on male body weight (BW) across the lifespan, whereas females more successfully counteract ELS-induced weight loss, possibly by adapting their microbiota, thereby stabilizing a balanced metabolome. Furthermore, the metabolic effects of a maternal HFD on BW are exclusively triggered by a dietary challenge in adult offspring and are more pronounced in males than in females. Overall, our study suggests that the female microbiota protects against an ELS challenge, rendering them more resilient to additional maternal- and adult nutritional stressors than males.

Impact of COVID-19 mandatory lockdown on maternal gestational weight gain and neonatal macrosomia rate at an academic medical center in Israel

Background In an effort to prevent the spread of coronavirus disease 2019 (COVID-19), governments restricted outdoor activities and imposed lockdown quarantine. This change in lifestyle probably affected individuals’ eating habits and physical activity. Objective To examine the effect of lockdown due to the COVID-19 pandemic on maternal antenatal weight gain, neonatal macrosomia, and other maternal and neonatal outcomes of women delivering at an academic medical center in Israel. Method A retrospective, two-period cohort study conducted at a university teaching medical center in Afula, Israel. The study period was between April and September 2020. This period signifies worsening in pandemic situations, during which citizens experienced strict prolonged lockdown measures. The parallel unexposed period (control period) was between April and September 2019. Singleton pregnancies delivered at >24 weeks were eligible. Primary outcome was incidence of macrosomia. Secondary outcomes included gestational weight gain, body mass index (BMI) at delivery, rates of gestational diabetes mellitus (GDM), mode of delivery, postpartum hemorrhage (PPH), and neonatal outcomes reflecting neonatal birth weight and condition at delivery. Results A total of 4,765 women were included, 2,442 in the study group and 2,323 in the control group. The incidence of macrosomia was significantly higher in 2020 (6.2%) than in 2019 (4.9%), (p = .048; OR: 1.29; 95% CI: 1.002– 1.65). Women gained significantly more weight (median 1 kg more), weighed more at delivery (median 1 kg), and had higher BMI at delivery in 2020 compared with those in 2019 (p < .01). The incidence of GDM was 9.5% and 8.5% in the study and control groups respectively (p = .26; OR: 1.12; 95% CI: 0.92–1.37). Greater percentage of women did not perform the glucose challenge test in 2020 (9.9%) compared with those in 2019 (7.5%) (p = .003, OR: 1.36; 95% CI: 1.11–1.67). The incidence of any hypertension related to pregnancy was significantly higher in 2020 compared to 2019 (5.8% vs 4.4% respectively, (p = .042; OR: 1.32; 95% CI: 1.02–1.71). The proportion of women who smoked during pregnancy was also significantly higher in 2020 than in 2019 (5.1% vs 3.7%, respectively, p = .02; OR: 1.40; 95% CI: 1.06–1.86). Delivery mode did not differ, while the incidence of PPH was significantly higher in 2020 than in 2019 (5.6% vs 3.4%, respectively, p = .001; OR: 1.65; 95% CI: 1.25–2.19). Neonatal condition at delivery was comparable. Conclusion COVID-19-related lockdown was associated with the increased rate of macrosomic infants. This indirect effect of the pandemic is probably related to poorer maternal antenatal metabolic health status. Long-term consequences should be further examined.

Influence of Maternal Metabolic Status and Diet during the Perinatal Period on the Metabolic Programming by Leptin Ingested during the Suckling Period in Rats.

We aimed to analyze the long-term metabolic effects of leptin supplementation at physiological doses during suckling in the offspring of diet-induced obese rats, together with the potential benefits of improving maternal diet during lactation. Thus, the offspring of: dams fed standard-diet (SD) (CON-dams), dams fed western-diet (WD) before and during gestation and lactation (WD-dams), and dams fed as WD-dams but moved to SD during lactation (REV-dams) were supplemented throughout suckling with leptin or vehicle, and fed SD or WD from weaning to four months. Under SD, leptin treatment significantly improved metabolic profile and body fat accumulation, with stronger effects in the male offspring of CON-dams and REV-dams. Under WD, the offspring of WD-dams presented metabolic alterations that were not evident in the offspring of REV-dams. Moreover, leptin supplementation improved glucose homeostasis in the male offspring of REV-dams. Conversely, leptin supplementation in females born to WD-dams and fed WD from weaning resulted in impaired insulin sensitivity and increased hepatic lipid content. These results highlight the importance of a balanced maternal diet during the perinatal period, especially lactation, for the subsequent metabolic health of the offspring and for the beneficial effects of leptin supplementation during suckling, more evident in the male offspring.

Perinatal Western-style diet alters serotonergic neurons in the macaque raphe nuclei.

The neurotransmitter serotonin is a key regulator of neurotransmission, mood, and behavior and is essential in neurodevelopment. Dysfunction in this important neurotransmitter system is connected to behavioral disorders such as depression and anxiety. We have previously shown that the developing serotonin system is sensitive to perinatal exposure to Western-style diet (WSD). To advance our hypothesis that perinatal WSD has a long-term impact on the serotonergic system, we designed a fluorescent immunohistochemistry experiment using antibodies against tryptophan hydroxylase 2 (TPH2) and vesicular glutamate transporter 3 (VGLUT3) to probe protein expression in the raphe subnuclei in 13-month-old Japanese macaques (Macaca fuscata; n = 22). VGLUT3 has been shown to be coexpressed in TPH2+ cells in the dorsal raphe (DR) and median raphe nucleus (MnR) of rodent raphe nuclei and may provide information about the projection site of serotonergic fibers into the forebrain. We also sought to improve scientific understanding of the heterogeneity of the serotonin production center for the central nervous system, the midbrain raphe nuclei. In this immunohistochemical study, we provide the most detailed characterization of the developing primate raphe to date. We utilize multi-level modeling (MLM) to simultaneously probe the contribution of WSD, offspring sex, and raphe anatomical location, to raphe neuronal measurements. Our molecular and morphological characterization revealed that the 13-month-old macaque DR is remarkably similar to that of adult macaques and humans. We demonstrate that vesicular glutamate transporter 3 (VGLUT3), which rodent studies have recently shown can distinguish raphe populations with distinct projection targets and behavioral functions, likewise contributes to the heterogeneity of the primate raphe. This study provides evidence that perinatal WSD has a long-term impact on the density of serotonin-producing neurons, potentially limiting serotonin availability throughout the brain. Due to the critical involvement of serotonin in development and behavior, these findings provide important insight into the mechanisms by which maternal nutrition and metabolic state influence offspring behavioral outcomes. Finally, these findings could inform future research focused on designing therapeutic interventions to optimize neural development and decrease a child's risk of developing a mental health disorder.

Effects of an integrated mobile health lifestyle intervention among overweight and obese women planning for pregnancy in Singapore: protocol for the single-arm healthy early life moments in Singapore (HELMS) study

IntroductionChanges in social and lifestyle factors have led to increasing rates of metabolic and mental health problems. We hypothesise that a transformation of the current maternal and child health system...