Exposure to toxins causes lasting damaging effects on the body. Numerous studies in humans and animals suggest that diet has the potential to modify the epigenome and these modifications can be inherited transgenerationally, but few studies investigate how diet can protect against negative effects of toxins. Potential evidence in the primary literature supports that caloric restriction, high-fat diets, high protein-to-carbohydrate ratios, and dietary supplementation protect against environmental toxins and strengthen these effects on their offspring's epigenome. Most notably, the timing when dietary interventions are given - during a parent's early development, pregnancy, and/or lifetime - result in similar transgenerational epigenetic durations. This implies the existence of multiple opportunities to strategically fortify the epigenome. This narrative review explores how to best utilize dietary modifications to modify the epigenome to protect future generations against negative health effects of persistent environmental toxins. Furthermore, by suggesting an ideal diet with specific micronutrients, macronutrients, and food groups, epigenetics can play a key role in the field of preventive medicine. Based on these findings, longitudinal research should be conducted to determine if a high protein, high-fat, and low-carbohydrate diet during a mother's puberty or pregnancy can epigenetically protect against alcohol, tobacco smoke, and air pollution across multiple generations.

The Developmental Origins of Health and Disease (DOHaD) concept postulates that maternal malnutrition can program offspring for dysfunction of multiple systems, including the liver. Maternal Protein Restriction (MPR) is a maternal malnutrition model that dysregulates catabolic hormones early in life, with long-term consequences on offspring such as hypertension and reproductive system cancers. Furthermore, studies evaluating sex-specific differences are scarce, especially considering the consequences of MPR on early life. Here, we investigated the impacts of MPR on hepatic phenotypic and molecular aspects of male and female rats at postnatal day (PND)21. The rats were divided into two groups: CTR, from dams that consumed a normal-protein diet (17 % protein), or GLLP, from dams that consumed a low-protein diet (6 % protein) throughout gestation and lactation. Our results demonstrated that MPR leads to an increase in collagen fibers, glycogen, and peroxiredoxin 1, in addition to a decrease in reticular fibers, mast cells, GSH, and MDA in the liver of male rats. In females, a reduction of reticular fibers and protein expression of hepatic peroxiredoxin 4 was observed. By contrasting these results with in silico analyses, we suggest that the main altered mechanisms in males are associated with oxidative stress, glycogen metabolism, and inflammatory responses. In females, a subtle dysregulation of antioxidant activity within the extracellular matrix was noted. Therefore, this work demonstrates sex-specific hepatic differences in post-weaning rats exposed to MPR, highlighting possible maternal modulations that lead males to be more affected, which may generate long-term effects on hepatic and systemic health.

Pediatric chronic kidney disease (CKD) is a growing concern that often originates early in life, yet significant challenges remain in translating clinical guidelines into real-world practice. World Kidney Day 2025 highlights the importance of early detection, but the three levels of preventive strategies commonly recommended for adults may not be directly applicable to children. Unlike adult CKD, primary prevention in pediatrics should focus on prenatal, neonatal, and early-life factors such as congenital anomalies of the kidney and urinary tract (CAKUT), preterm birth, maternal health, and environmental exposures. Secondary prevention, involving early detection through screening, is crucial, yet the effectiveness of mass urinary screening in children remains a subject of global debate. Several key challenges persist, including the accurate estimation of glomerular filtration rate (eGFR), consistent definition and diagnosis of pediatric hypertension, identification of reliable biomarkers, and targeted screening in specific pediatric populations. Although clear guidelines exist to manage CKD progression and enhance quality of life, a critical gap remains between what is known and what is practiced. Closing this gap requires robust evidence to inform best practices, improve health-related quality of life, and advance pediatric kidney replacement therapies. To protect and improve kidney health for every child worldwide, these challenges must be acknowledged, and sustainable, evidence-based solutions must be developed and implemented without further delay.

Simultaneous inhibition of α-glucosidase (α-Glu) and protein tyrosine phosphatase 1B (PTP1B) offers a promising therapeutic strategy for type 2 diabetes (T2D). Despite the natural product potential in T2D management, existing screening methods predominantly target single enzymes, whereas multi-enzyme approaches are often costly and less practical. A simple, cost-effective method for identifying multi-target inhibitors is therefore urgently needed.

A new dual-enzyme inhibitor screening system was developed to screen for α-Glu and PTP1B dual inhibitors in natural product extracts. This system, combining immobilized a hollow fiber and an ultrafiltration centrifugal device with mass spectrometry detection, enabled simultaneous screening of dual-enzyme inhibitors with a single sample injection. The drug first reacted with α-Glu in a hollow fiber, then passed through the fiber and reacted with free PTP1B, in a process mimicking the body's absorption and distribution processes more closely than traditional methods. Enzymatic reaction conditions were optimized with the known dual inhibitor (-)-epigallocatechin-3-O-gallate (EGCG). Subsequently, the method was used to screen potential inhibitors in white tea, Fructus Cnidii, and Citri Reticulatae Pericarpium extracts. For immobilized α-Glu, free α-Glu, and PTP1B, the calculated Michaelis-Menten constants (Km) were 5.75, 5.88 and 1.87 mM, respectively. After ligand fishing, molecular docking and inhibition assays were used to validate potent inhibitors. Finally, four catechin compounds were identified: EGCG, (-)-epicatechin gallate (ECG), catechin and (-)-epicatechin. Their IC50 values for α-Glu inhibition were 0.67, 0.79, 323.25, and 328.25 μM, respectively. For PTP1B inhibition, their IC50 values were 0.58, 0.84, 4.71, and 3.69 μM, respectively. These results demonstrated that the hollow fiber ultrafiltration system was a reliable method for screening dual-target inhibitors.

Our dual-enzyme reactor, the first system designed for dual-target screening, provided a simple, cost-effective, sensitive, reproducible, and selective approach for identifying dual-enzyme inhibitors. Its outstanding applicability to natural product extracts highlighted its potential for broad application in drug discovery.

The Developmental Origins of Health and Disease (DOHaD) concept has emerged as an interdisciplinary framework that explores how early-life events shape long-term health and disease risk. Rooted in the Thrifty Phenotype hypothesis proposed by Barker and Hales, DOHaD builds upon centuries of philosophical and scientific thought. Central to DOHaD is the concept of phenotypic plasticity, which explains how organisms adapt their biological characteristics in response to environmental stimuli, particularly during critical developmental periods. In this context, this review aims to analyze the historical evolution of phenotypic plasticity, its theoretical foundations, and its role in health and disease. After reviewing the literature on scope, we summarize key contributions from evolutionary biology, genetics, and epigenetics, examining theories from Lamarck, Darwin, Mendel, and Waddington to contemporary perspectives in DOHaD. Understanding that early-life events can lead to adaptations which may have short-term benefits but potentially increase the likelihood of diseases in adulthood highlights the importance of targeted preventive interventions. Additionally, individual variations in response to environmental stimuli reinforce the complexity of adaptive mechanisms. Thus, understanding the intricate relationship between phenotypic plasticity, early-life exposures, and disease risk is essential for developing preventive interventions and public health strategies. The challenge remains in translating these findings into effective healthcare policies and clinical applications, ensuring improved quality of life and disease prevention across generations.

Low birth weight continues to be a significant cause of perinatal morbidity and mortality, contributing to 80% of neonatal deaths in low and middle-income countries. To the authors' knowledge, no prior study has estimated the regional and sub-regional prevalence of low birth weight and its determinants in these settings. Therefore, this study aimed to examine the pooled and regional estimates of low birth weight in low and middle-income countries.

We used a weighted sample of 343,898 birth records, taken from the pooled demographic and health surveys conducted from 2015 to 2022 in 44 low and middle-income countries. Overall and sub-regional trends in low birth weight estimates were presented using a line graph. A multilevel mixed-effect analysis was done to identify determinants of low birth weight. Model comparison was performed using deviance and log-likelihood values, and statistical significance was determined at a P-value of less than 0.05.

The overall prevalence of low birth weight births was 13.7% [95% CI: 13.5%-13.8%], showing significant variations among countries and regions. Asia region had the highest prevalence at 16%, followed by Latin America, the Caribbean, and Europe at 11.5%, and Africa at 9.5%. Our study also indicated a decline in low birth weight from 11.4% to 9.5% over eight-year periods, with no consistent trend observed. Furthermore, factors such as health insurance, household wealth, maternal age, access to healthcare facilities, maternal education, neonate's sex, prenatal care, and antenatal iron supplementation were found to be statistically associated with low birth weight.

Our findings highlight the significant burden of low birth weight births, with notable variations in rates among countries and regions. The study also reveals a slight decline in low birth weight over time, although no consistent trend was observed. Importantly, maternal and household factors play significant roles in influencing low birth weight. Thus, addressing these factors through targeted interventions and policies could help reduce the incidence of low birth weight births in LMICs.

There is growing evidence that preterm infants born to mothers with chorioamnionitis (CAM) have increased risk of various neonatal morbidities and long-term neurological disorders; however, the effect of CAM on postnatal growth remains insufficiently investigated. This study evaluated the effect of histological CAM on postnatal growth trajectories in very preterm infants using a nationwide neonatal database in Japan.

A multicenter retrospective study was conducted using clinical data of 4220 preterm neonates who weighed ≤ 1500 g and were born at < 32 weeks of gestation between 2003-2017 (CAM group: n = 2110; non-CAM group: n = 2110). Z-scores for height and weight were evaluated at birth and 3 years of age. Univariable and multivariable analyses were conducted to evaluate the effect of histological CAM on ΔZ-scores of height and weight during the first three years with a stratification by infant sex and the stage of histological CAM.

Multivariable analyses showed that histological CAM was associated with accelerated postnatal increase (ΔZ-score) in weight (β coefficient [95% confidence interval]; 0.10 [0.00 to 0.20]), but not in height among females (0.06 [- 0.04 to 0.15]) and not in height and weight among males (0.04 [- 0.04 to 0.12] and 0.02 [- 0.07 to 0.11], respectively). An interaction analysis demonstrated no significant difference in the effect of histological CAM on the ΔZ-scores of height and weight during the first three years between male and female infants (height, p = 0.81; weight p = 0.25).

Intrauterine exposure to maternal CAM contributes to accelerated postnatal weight gain in female preterm infants during the first three years.

This article examines the human body's adaptive responses to obesity from biological, behavioral, and evolutionary perspectives. It explores how ancient survival mechanisms, such as fat storage during scarcity, have persisted but become maladaptive in modern contexts of food abundance and sedentary lifestyles. Using the Thrifty Gene Hypothesis and General Adaptation Syndrome (GAS), the study investigates how chronic stress and genetic predispositions contribute to obesity. Chronic stress, as described in GAS, is linked to obesity through mechanisms like prolonged cortisol elevation, which promotes fat storage, particularly in the abdominal region, and disrupts hunger and satiety regulation. The article also explores the possibility that contemporary chronic stress may cause the body to buffer stressful conditions through fat accumulation. While the Thrifty Gene Hypothesis suggests that genetic traits evolved to optimize energy storage during scarcity, contributing to obesity in modern environments, it remains controversial. Critics argue that it oversimplifies obesity's causes, such as lifestyle and environmental factors. Although genetic variations influencing obesity susceptibility continue to evolve, the physiological mechanisms of fat storage and stress adaptation have remained largely unchanged since ancient times.

The fetal brain is susceptible to programming effects during pregnancy, potentially leading to long-term consequences for offspring's cognitive health. Fructose (FRU) intake is thought to adversely affect fetal brain development, whereas physical exercise before and during pregnancy may be protective. Therefore, this study aimed to assess biochemical and genotoxic changes in maternal hippocampi and behavioral, genotoxic, and biochemical alterations in offspring hippocampi. Seventy female mice were exposed to FRU (20%/L) and/or voluntary physical exercise (VPE) pre-pregnancy for eight weeks, and then mated and exposure was continued until weaning. Offspring were evaluated at 60 days old using behavioral test, genotoxic, and biochemical markers. FRU-induced long-term memory impairment in male offspring, which was alleviated by VPE. VPE mitigated DNA damage from maternal FRU consumption in both maternal and offspring hippocampi in female offspring, VPE increased levels of apurine/apyrimidinic endonuclease 1, erythroid nuclear factor 2, and cAMP response element binding proteins, whereas in males, 8-oxoguanine DNA glycosylase-1 levels upregulate. FRU consumption led to oxidative stress and antioxidant defense alterations in offspring, while VPE mitigated these effects. Telomere shortening was observed in male offspring from mothers who consumed FRU during pregnancy. Our findings suggest that exposure to FRU during (pre)pregnancy and lactation has adverse effects on offspring's hippocampi later in life, and VPE has a protective effect. Overall, the study underscores the significance of maternal dietary and physical habits on long-term offspring health, with an emphasis on implications for adult cognitive function.

While obesity rates increase worldwide, physical activity levels are reduced. Obesity and physical inactivity may be inversely related to the production of reactive oxygen species (ROS) and cause oxidative stress in the central nervous system. In this study, we aimed to investigate the effects of aerobic physical exercise on the oxidative balance of the prefrontal cortex of rats subjected to overnutrition during lactation. For this, male Wistar rats were subjected to overnutrition during lactation between postnatal day 3 to 21. On postnatal day 23, the two groups of animals were subdivided into trained and untrained animals. Trained rats were subjected to a treadmill training protocol for four weeks, five days/week, 60 min/day, at 50% of maximum running capacity. Our findings demonstrate that overnutrition impairs REDOX balance in the prefrontal cortex through increased prooxidants and reduced antioxidant defenses. On the contrary, exercise tends to restore most of these measures to control levels, possibly due to the increase in mRNA levels of Sirt1 and reduction in Il-6 in the prefrontal cortex. Overnutrition causes oxidative stress in the prefrontal cortex, while exercise re-covers most of its adverse effects through activating anti-inflammatory mechanisms.

Obesity is a global health crisis, with increasing evidence linking environmental factors such as exposure to endocrine-disrupting chemicals (EDCs) to its development. This study examines the transgenerational effects of exposure to the model obesogen, tributyltin (TBT), on obesity and metabolic health, specifically focusing on how these effects interact with a diet modeling the 50th percentile of US dietary consumption [the Total Western Diet (TWD)]. Pregnant F0 dams were exposed to TBT, and their offspring were subjected at adulthood to different diets, including a high-fat diet and TWD, across multiple subsequent generations (F1-F3). We found that TBT exposure predisposed male offspring to increased fat accumulation, insulin resistance, and metabolic dysfunction, effects that were exacerbated by the TWD. Notably, male offspring displayed elevated leptin levels, hepatic fibrosis, and inflammatory responses under TWD exposure, suggesting an additive or synergistic relationship between obesogen exposure and dietary fat intake. These transgenerational effects were largely absent in female offspring, underscoring sex-specific vulnerabilities to environmental and dietary factors. Our results demonstrated that the combination of prenatal TBT exposure and TWD amplifies metabolic disturbances across generations, highlighting the need to consider both environmental chemicals and dietary patterns in addressing the obesity pandemic. This study underscores the critical role of early-life EDC exposures and dietary factors in shaping long-term metabolic health and the potential for transgenerational programming of susceptibility to obesity and metabolic disorders.

Is the ratio of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) comparable between children following ART and natural conception (NC)?

Children conceived by frozen embryo transfer (FET) had slightly lower VAT/SAT ratios than children following NC; no difference in VAT/SAT ratio was observed in children born following fresh embryo transfer (Fresh-ET) as compared to those born from NC.

The VAT/SAT ratio is closely related to the metabolic profile, with a high ratio increasing the risk of cardiometabolic diseases. To our knowledge, no studies have reported the VAT/SAT ratio in children following ART.

This prospective exploratory observational cohort study included 150 singletons aged 7-10 years. All children were born in eastern Denmark. The study was conducted between November 2018 and August 2020.

This is a sub-study of the 'Health in Childhood following Assisted Reproductive Technology' (HiCART) study. The children were conceived after FET (n = 50), Fresh-ET (n = 50), and NC (n = 50), and children conceived by NC were matched to ART children by sex and birth year. The children underwent abdominal MRI for the quantification of abdominal adipose tissues along with measurements of blood pressure, fasting blood samples, anthropometric measurements, and dual-energy X-ray absorptiometry scans. The volumes of VAT and SAT were semi-automatically quantified, blinded for the mode of conception. The level of statistical significance was set to a P-level below 0.05. Multivariable linear regression analysis of the VAT/SAT ratio was performed to adjust for confounders in a five-step approach: Model 1: Adjusted for child age and sex; Model 2: Model 1 plus maternal age at delivery and maternal BMI at pregnancy; Model 3: Model 2 plus birth weight and child BMI; Model 4a: Model 3 plus maternal educational level; Model 4b: Model 3 plus pubertal status. The confounders were selected based on their association with metabolic risk factors according to previous studies.

As previously reported in the HiCART studies, there were no differences between the groups in anthropometric measurements including BMI, lean body mass, blood pressure, or triglycerides. The crude VAT/SAT ratio differed significantly between the three groups (mean (SD); FET 0.26 (0.08), Fresh-ET 0.29 (0.07), NC 0.30 (0.08), ANOVA-P = 0.014). Pairwise comparison revealed that children conceived after FET had lower crude VAT/SAT ratio than children conceived after NC (P = 0.007) with a mean difference of -0.04, 95% CI (-0.07; -0.01), and a tendency for a lower VAT/SAT ratio as compared to the Fresh-ET group (P = 0.059) with a mean difference of -0.03, 95% CI (-0.06; 0.00). Lower VAT/SAT ratio in FET as compared to NC remained after adjustment for child age and sex (Model 1: -0.04 (-0.07; -0.01)), maternal age at delivery and maternal BMI at pregnancy (Model 2: -0.04 (-0.07; -0.01)), birth weight and child BMI (Model 3: -0.04 (-0.07; -0.01)), maternal educational level (Model 4a: -0.05 (-0.08; -0.01)), and puberty (Model 4b: -0.04 (-0.08; -0.01)) in a five-step approach. Repeated analysis of twenty MRI scans showed good intra-rater repeatability of VAT and SAT volume quantifications.

The sample size was relatively small and selection bias due to differences in intrinsic factors between the three groups may affect the results. Well-described confounders from the literature were included in the multivariable regression analysis, but the observational nature of this cohort study hinders the establishment of causality.

Reassuringly, this study found no clinically important difference in VAT/SAT ratio between children following ART (both FET and Fresh-ET) and NC, although a small but significantly lower VAT/SAT ratio was found in children born after FET compared with NC children.

A.R.O was supported by a scholarship from Herlev-Gentofte Copenhagen University Hospital. The study was funded by grants from Novo Nordisk Foundation (NNF18OC0034092, NFF19OC0054340) and The Research Foundations at Rigshospitalet and Herlev-Gentofte Copenhagen University Hospital (unrestricted grant). A.P. has received grants (via her institution), honoraria, and consulting fees from Gedeon Richter, Ferring Pharmaceuticals, and Merck A/S, as well as consulting fees from Novo Nordisk A/S and Cryos, honoraria from Organon and support for attending meetings (via her institution) from Gedeon Richter. K.M.M. has received royalties from Gyldendal and consulting fees from The National Board of Wealth and Welfare in Sweden, in addition to honoraria from Novo Nordisk A/S and Lundbeck A/S, and serves as a medical expert for the Ministry of Justice, Department of Civil Affairs. All other authors declare no conflicts of interest.

ClinicalTrials.gov identifier: NCT03719703.

Growing consumption of processed foods may cause a greater risk of excessive dietary phosphate intake. The increased dietary phosphate intake as a food additive in the periconceptional period may affect the children's future health. Here, we investigated the effects of maternal excess dietary phosphate intake on offspring in C57BL/6J mice. Female mice were fed a control diet (CP, 0.8% phosphate) or a high-phosphate diet (HP, 1.5% phosphate) for either 21 days during pre-pregnancy or almost 20 days during pregnancy. After weaning, offspring were raised on the CP diet. Relative to the CP groups, offspring from dams fed HP during pre-pregnancy or pregnancy showed decreased urinary phosphate excretion without significant changes in either plasma phosphate level or renal sodium-dependent phosphate transporter mRNA expression at 3 or 10 weeks. However, mRNA expression of intestinal sodium-dependent phosphate transporter was decreased, suggesting that the reduced urinary phosphate excretion was due to decreased absorption of intestinal phosphate. Interestingly, offspring in the HP groups also demonstrated significant differences in plasma levels of parathyroid hormone, fibroblast growth factor 23, and vitamin D. To our knowledge, this is the first report to show that maternal excess intake of dietary phosphate in the periconceptional period disturbs phosphate metabolism in offspring.

Cardiovascular-kidney-metabolic syndrome (CKMS) has become a significant global health challenge. Since CKMS often originates early in life, as outlined by the developmental origins of health and disease (DOHaD) concept, prevention is a more effective strategy than treatment. Various animal models, classified by environmental exposures or mechanisms, are used to explore the developmental origins of CKMS. However, no single model can fully replicate all aspects of CKMS or its clinical stages, limiting the advancement of preventive and therapeutic strategies. This review aims to assist researchers by comparing the strengths and limitations of common animal models used in CKMS programming studies and highlighting key considerations for selecting suitable models.

This study aimed (1) to determine the degree of correlation between 2D and 3D estimated fetal weight (EFW) and neonatal birth weight (BW) among borderline small fetuses and (2) to compare the accuracy and precision of 2D and 3D EFW in BW prediction.

A retrospective cohort study evaluated fetuses who had an ultrasound performed between January 2017 and September 2021 at a tertiary maternal center. All singleton pregnancies with 3D EFW within 4 weeks of delivery were included. Fetuses with known structural or genetic abnormalities were excluded. Pearson's correlation coefficients were determined for both 2D and 3D EFW to BW then compared using Williams' test and Fisher r to z transformation, where applicable. Mean percent difference and standard deviation were used to assess the accuracy and precision, respectively, of 2D and 3D EFWs in BW prediction.

Two hundred forty-eight pregnancies were included. Ultrasound studies were performed with a median interval of 2 weeks (IQR 1, 3) between ultrasound and delivery. Both 2D and 3D estimated fetal weights showed a significant correlation with birth weight (r = 0.74 and r = 0.73, respectively), indicating similar accuracy between the two techniques.

Two-dimensional and three-dimensional EFWs performed similarly in the prediction of BW in borderline small fetuses.

This paper explores conflicting perspectives on the adaptive significance of phenotypic plasticity during fetal and early postnatal development and the impact that stressors experienced during this critical early-life period have on later-life morbidity and mortality risk.

The sample (n = 216) comprised archeologically-recovered human skeletons. A geometric morphometric (GM) method was employed to evaluate first permanent molar (M1) fluctuating asymmetry (FA) and provide a proxy for early-life stress. Shifts in later-life physiology were inferred through two inflammatory lesions: periosteal new bone formation (PNBF) and periodontal disease (PD). To explore mortality risk, age-at-death was estimated through dental development for skeletally immature individuals (n = 104) and through senescent skeletal changes for mature skeletons (n = 112).

Significant differences were found in M1 FA between groups, with the immature cohort associated with elevated FA. Within-group analysis revealed age-at-death in the immature group had a significant positive relationship with M1 FA and PD presence. In the mature group, alongside sex and the co-occurrence of PD and PNBF, FA was a significant predictor of a shorter life. Higher FA was also associated with active and bilaterally expressed PNBF.

It is theorized that early-life stress, if survived, programmed a hyperinflammatory response to environmentally-mediated physiological perturbations which increased the chances of survival during subsequent development but also elevated later-life mortality risk. Findings demonstrate a complicated relationship between developmental stress and physiological shifts that helps to illustrate the adaptive significance of early-life programming and support the Thrifty Phenotype hypothesis.

For the survival and efficient breeding of wild-living animals, it is crucial to predict seasonal changes and prepare appropriate physiological functions and neurobehavioral mechanisms. In mammals, photoperiod serves as a reliable cue for seasonal changes in the environment, primarily transmitted by melatonin. This review focuses on the seasonal adaptation of mammalian development, specifically the effect of early-life photoperiod on reproductive, somatic, and neurobehavioral development in small- and large-sized mammals. Prediction of seasons through early-life photoperiod is particularly important for small mammals, which have relatively short longevity, to adjust their maximum growth and breeding ability in appropriate seasons during the birth year or the following round. Brain plasticity, as well as cognitive and emotional behaviors, are also highly modulated by early-life photoperiods for successful mating and spatial memory for foraging. This review first summarizes the basic knowledge and recent progress in the programming and epigenetic regulatory mechanisms of reproductive and neurobehavioral development in small mammals, including C57BL/6J mice, which cannot produce detectable amounts of melatonin. The review then focuses on the influence of perinatal environmental conditions or birth season on adult phenotypes in large livestock and humans. Studies have advanced on the concept of the developmental origins of health and disease (DOHaD). Evidence from large mammals suggests that the prediction of seasons is crucial for high-fitness functions over several years. Finally, this review discusses the association of the season of birth with life course physiology and diseases in humans, and the possible mechanisms.

The developmental origins of adult disease theory support the concept that undernourished fetuses are at risk of developing metabolic syndrome due to the energy-saving 'Thrifty Phenotype'. This metabolic plasticity represents an evolutionary adaptation that allows individuals to resist the intense pressure caused by cyclically recurring periods of nutritional deprivation. A comprehensive review was conducted following an extensive literature search in the PubMed/Medline and EMBASE databases concerning reports on fetal/intrauterine growth restriction and its metabolic-related long-term outcomes. We only included articles written in English that were published before 1 July 2024. There are several underlying mechanisms and metabolic and endocrine adjustments shaped by the perinatal environment, and they all contribute to progression towards adult disease. From in utero malnutrition or other insults during the fetal period to fetal programing and postnatal catch-up growth, it is difficult to identify the exact moment when this adaptative phenomenon meant to assure fetal survival and to set children on their own physiological growth curves lose its beneficial effect, establishing the trajectory to obesity, insulin resistance, and other hallmarks of metabolic syndrome. With clinical correspondence to an altered body mass, composition, and eating behaviors, it is evident that the metabolic complications linked to FGR are intricate and arise from disturbances in several pathways and organs, but the underlying processes responsible for the long-term consequences are just starting to be understood. The lack of continuity in perinatal-to-pediatric FGR research sets the challenge of exploring new directions in future scientific opportunities. These will hopefully represent a cornerstone in the management of FGR-related metabolic disorders in children, preventing these disorders from evolving into adult disease.

Maternal nutrition during pregnancy plays a pivotal role in influencing both maternal and fetal health, impacting neonatal anthropometric outcomes and long-term disease susceptibility. An advanced maternal age (AMA ≥ 35 years) has been linked to increased risks of obstetric complications and adverse neonatal outcomes, yet its specific nutritional profile remains underexplored. Background/Objectives: This study aimed to evaluate the nutrient and polyphenol intakes of women at an AMA compared to those of a younger control group and to investigate associations with neonatal anthropometric measures. Methods: A cohort of 200 pregnant women, stratified into AMA and control groups, completed a food frequency questionnaire during the second trimester. Neonatal anthropometric data were collected at delivery. Results: Intakes of fiber, zinc, copper, selenium, vitamins E, B1, B3 and folate were lower in the AMA group in comparison with the control values. Negative correlations were found between fiber, vitamin A and vitamin E and the head circumference of the newborn, with fiber being identified as a potential predictor of this parameter. Conclusions: Despite some limitations, such as the fact that the FFQ was completed only once during pregnancy and the cross-sectional design of the study, the findings highlight notable nutritional deficiencies among AMA women, which may influence neonatal outcomes such as head circumference. These results underscore the need for nutritional guidelines and supplementation strategies tailored to pregnant women over 35 years of age.

Epidemiological surveys indicate an increasing incidence of type 2 diabetes mellitus (T2DM) among children and adolescents worldwide. Due to rapid disease progression, severe long-term cardiorenal complications, a lack of effective treatment strategies, and substantial socioeconomic burdens, it has become an urgent public health issue that requires management and resolution. Adolescent T2DM differs from adult T2DM. Despite a significant increase in our understanding of youth-onset T2DM over the past two decades, the related review and evidence-based content remain limited.

To visualize the hotspots and trends in pediatric and adolescent T2DM research and to forecast their future research themes.

This study utilized the terms "children", "adolescents", and "type 2 diabetes", retrieving relevant articles published between 1983 and 2023 from three citation databases within the Web of Science Core Collection (SCI, SSCI, ESCI). Utilizing CiteSpace and VoSviewer software, we analyze and visually represent the annual output of literature, countries involved, and participating institutions. This allows us to predict trends in this research field. Our analysis encompasses co-cited authors, journal overlays, citation overlays, time-zone views, keyword analysis, and reference analysis, etc.

A total of 9210 articles were included, and the annual publication volume in this field showed a steady growth trend. The United States had the highest number of publications and the highest H-index. The United States also had the most research institutions and the strongest research capacity. The global hot journals were primarily diabetes professional journals but also included journals related to nutrition, endocrinology, and metabolism. Keyword analysis showed that research related to endothelial dysfunction, exposure risk, cardiac metabolic risk, changes in gut microbiota, the impact on comorbidities and outcomes, etc., were emerging keywords. They have maintained their popularity in this field, suggesting that these areas have garnered significant research interest in recent years.

Pediatric and adolescent T2DM is increasingly drawing global attention, with genes, behaviors, environmental factors, and multisystemic interventions potentially emerging as future research hot spots.

Protein deficiency in the diet during pregnancy and lactation has a serious impact on the offspring by programming a predisposition to such serious diseases as hypertension and type 2 diabetes mellitus. In our study, we examined liver ultrastructure of rat pups at ages 2, 21, and 40 days with maternal protein deficiency. Body weight of the pups progressively lagged behind the control throughout the experiment, and the timing of eye opening indicated a slowdown of development. In the liver of 2-day-old animals, the proportion of hematopoietic cells at early stages of differentiation was higher as compared to the control. At the ultrastructural level, no obvious pathological changes were revealed, but a decrease in the amount of organelles was observed simultaneously with accumulation of lipids and glycogen. In the course of the experiment, a progressive decrease in the amount of the rough endoplasmic reticulum and ribosomes and increasing accumulation of glycogen in the cytoplasm of hepatocytes were noted. The most pronounced difference in ultrastructure between periportal and pericentral hepatocytes of control rat pups was detected on the 40th day of development, whereas in the low-protein diet group, the difference was weakly pronounced throughout the experiment. Thus, we showed that with prenatal and early postnatal protein deficiency, the growth and development of rat pups slows down, and glycogen accumulates excessively in the liver concurrently with a decrease in the amount of organelles.

Malnutritional stress during gestation is a well-established driver of metabolic disfunction in offspring. Extended exposure to malnutrition requires metabolic plasticity as the animal shifts toward a catabolic state. In this paper we demonstrate the influence of malnutrition throughout gestation on uterine artery hemodynamics and the metabolism of the dam and neonate. We hypothesized that gestational malnutrition reduces blood flow of the maternal uterine artery and regulates the metabolic profile of the dam and offspring. Further, the combination of these factors consequently influences the concentration of metabolites in the cerebrospinal fluid of the neonate at birth. To test our hypotheses, pregnant cows caring a single female fetus were assigned to treatments by age and body condition score to one of three individually-fed dietary treatments: Underfed, Control, or Overfed throughout gestation. Uterine blood flow was measured via transrectal Doppler ultrasonography in late gestation. Blood samples were collected from dams throughout gestation, and blood and cerebrospinal fluid were collected from neonates at birth to analyze concentration of metabolites. In the current report, we reveal that maternal malnutrition regulates uterine artery hemodynamics and the maternal metabolic profile throughout gestation. This is the first report to demonstrate that maternal undernutrition leads to an increase in the concentration of urea nitrogen in neonates. Finally, a concentration gradient of metabolites from the dam to neonatal cerebrospinal fluid was observed, which may have potential implications for central nervous system development. These findings not only illustrate the complexity of the maternal-to-fetal interaction required to support the growth of the fetus and homeostasis of the dam but also reveals a novel avenue for investigating the influence of protracted maternal malnutrition on metabolic pathway preferences in offspring. Moreover, these findings are of paramount importance in the development of intervention strategies for morbid neonates.

The double burden of malnutrition (DBM), characterised by the coexistence of undernutrition and overnutrition, poses a significant public health challenge, particularly in low- and middle-income countries. India, being one of these countries, faces a rising burden of malnutrition, with persistently high levels of stunting and a significant increase in overweight and obesity among children under 5 years old.

To estimate the prevalence of DBM and associated sociodemographic factors among children aged 0-5 years in India, using data from the National Family Health Survey-4 (NFHS-4).

A secondary data analysis of the NFHS-4 (2015-2016) a nationally representative cross-sectional data was conducted. The study population consisted of 57 951 children aged 0-5 years, and anthropometric data were extracted from the NFHS-4 India database. Child growth indicators, including stunting, overweight, obesity and DBM were analysed using internationally recognised WHO Child Growth Standards. Descriptive statistics, graphical representations and the χ2 test of significance were employed to explore the relationships between DBM and various factors.

The analysis of data from the NFHS-4 for India revealed that the prevalence of the DBM among children aged 0-5 years was 2.3% (95% CI 2.2% to 2.5%).

While the prevalence of DBM among children under 5 years of age in India is relatively low at 2.3%, the implications of this issue are far-reaching and enduring. Despite appearing modest, addressing DBM requires sustained attention and comprehensive strategies. Extensive research with larger samples is essential for understanding complex challenges.

Evolutionary medicine emerged in the late twentieth century, integrating principles of natural selection and adaptation with the health sciences. Today, with a rapidly widening gap between the biology of Homo sapiens and its environment, maladaptation or maladaptive disorders can be detected in almost all diseases, including liver dysfunction. However, in hepatology, as in most medical specialties, evolutionary considerations are neglected because the majority of the medical community is not familiar with evolutionary principles. The aim of this brief review is to highlight an evolutionary approach that may facilitate understanding various liver diseases.

Fetal growth restriction (FGR) is a risk factor for obesity in adult life. Importantly, growth-restricted females are more prone to obesity than males. The mechanisms involved in this sexually dimorphic programming are not known. Previously, we have demonstrated that ambient hyperthermia (40°C) led to placental insufficiency and significant FGR, and the perirenal adipose tissue undergoes sexually dimorphic gene expression. We demonstrated that males undergo significant changes in gene expression with growth restriction. This was not the case in females. We have also demonstrated that the isolated preadipocytes from male FGR (MFGR) have reduced differentiation potential compared to control males & females and female FGR (FFGR). Thus, we hypothesized that growth restriction differentially programs gene expression and genetic pathways in perirenal preadipocytes, which reduces their differentiation potential in male fetuses in a sexually dimorphic manner. We created FGR by exposing pregnant sheep to ambient hyperthermia. After isolating preadipocytes from perirenal adipose tissue, we differentiated them following published protocols. We examined the gene expression before and after differentiation from control male, control female, MFGR, and FFGR female. We also compared our data with other published studies in mouse and human preadipocytes. Our results demonstrate that a set of 21 genes altered with preadipocyte differentiation to mature adipocytes is common in adipose tissue from both sexes, humans, mice, and sheep, at different organismal ages (embryonic, fetal, and adult) and different sites (subcutaneous inguinal, pancreatic, perirenal). We also demonstrate that female FFGR fetuses demonstrate all these 21 genes altered similar to control males and females; however, MFGR fetuses have six genes (Dgat2, Fabp4, Lipe, Lrrfip1, Spred3, and Thrsp) that are not changed with preadipocyte differentiation to mature adipocyte. These genes may be responsible for reduced differentiation potential and obesity in FGR males compared to FGR females. Another important finding of the present study is that Lrrfip1, known to be associated with obesity, was upregulated with FGR and requires further investigation. Overall, our studies provide several target genes that may play a crucial role in reducing the risk of MFGR for obesity.

While physical activity reduces the risk for chronic disease development, evidence suggests those experiencing early life growth-restriction do not express positive adaptations in response to physical activity. The purpose of this study was to examine the effects of low birthweight (LBW) on markers of chronic disease, adult physical activity, and the response to physical activity engagement in a longitudinal human cohort study. Data from the Framingham Offspring Cohort were organized to include participants with birthweight, physical activity, and chronic disease biomarker/treatment data available at two timepoints (exam 5 and exam 9, 19-year difference). A two-way ANCOVA was performed to determine the association of LBW and sex on physical activity engagement (63.0% female, 10.4% LBW). A multinomial logistic regression was performed to examine the associations of low birthweight and sex on chronic disease development while adjusting for physical activity. LBW was associated with elevated blood glucose and triglycerides (Exam 9). Though not statistically significant (p = 0.08), LBW females potentially spent more time in sedentary activity at exam 5 than LBW males and normal birthweight (NBW) females. LBW males spent significantly more time (p = 0.03) sedentary at exam 9 compared to NBW males and LBW females. There were no differences in the likelihood of chronic disease treatment between groups. Chronic disease biomarkers remained elevated when adjusted for total physical activity. In conclusion, LBW participants in the Framingham Offspring Cohort were not more likely to be treated for chronic diseases when controlling for physical activity engagement, though biomarkers of chronic disease remained elevated.

Background/Objectives: Childhood obesity is a global health problem that affects at least 41 million children under the age of five. Increased BMI in children is associated with serious long-term health consequences, such as type 2 diabetes, cardiovascular disease, and psychological problems, including depression and low self-esteem. Although the etiology of obesity is complex, research suggests that the diet and lifestyle of pregnant women play a key role in shaping metabolic and epigenetic changes that can increase the risk of obesity in their children. Excessive gestational weight gain, unhealthy dietary patterns (including the Western diet), and pregnancy complications (such as gestational diabetes) are some of the modifiable factors that contribute to childhood obesity. The purpose of this narrative review is to summarize the most important and recent information on the impact of the diet and lifestyle of pregnant women on the risk of childhood obesity. Methods: This article is a narrative review that aims to summarize the available literature on the impact of pregnant women's diet and lifestyle on the risk of obesity in their offspring, with a focus on metabolic and epigenetic mechanisms. Results/Conclusions: Current evidence suggests that a pregnant woman's lifestyle and diet can significantly contribute to lowering the risk of obesity in their offspring. However, further high-quality research is needed to understand better the metabolic and epigenetic relationships concerning maternal factors that predispose offspring to obesity.

Living systems are capable on the one hand of eliciting a coordinated response to changing environments (also known as adaptation), and on the other hand, they are capable of reproducing themselves. Notably, adaptation to environmental change requires the monitoring of the surroundings, while reproduction requires monitoring oneself. These two tasks appear separate and make use of different sources of information. Yet, both the process of adaptation as well as that of reproduction are inextricably coupled to alterations in genomic DNA expression, while a cell behaves as an indivisible unity in which apparently independent processes and mechanisms are both integrated and coordinated. We argue that at the most basic level, this integration is enabled by the unique property of the DNA to act as a double coding device harboring two logically distinct types of information. We review biological systems of different complexities and infer that the inter-conversion of these two distinct types of DNA information represents a fundamental self-referential device underlying both systemic integration and coordinated adaptive responses.

Attention-deficit/hyperactivity disorder (ADHD) is associated with lower birth weight, but also with obesity in childhood. Findings on the direction of this association are mixed. This study investigated the relationship between weight and ADHD from birth across development.

We used data from the Millennium Cohort Study (MCS), collected at 7 time points between age 9 months and 17 years. ADHD diagnosis status and scores on the Strength and Difficulties Questionnaire (SDQ) were used to create an ADHD group and a control group. Random intercept cross-lagged panel models were conducted in female individuals (n = 4,051) and male individuals (n = 3,857) to examine bidirectional associations between body mass index (BMI) z scores and SDQ scores between ages 3 and 17 years. Analyses were adjusted for common risk factors for ADHD and obesity, such as sex assigned at birth, multiple births, and ADHD medication status.

Children in the ADHD group were significantly lighter in weight at birth than the control group (t[5674] = 2.65, 95% CI = 0.02, 0.14, p = .008) and were significantly more likely to have obesity at age 5 years onward (odds ratio range = 1.57-2.46, relative risk range 0.98-2.29). Path analyses conducted separately for male and female individuals showed that higher ADHD symptoms in female individuals at ages 7, 11, and 14 years significantly predicted higher BMI z scores at ages 11, 14, and 17 years, respectively. In male individuals, this association was seen only between ages 11 and 14 years (β = 0.07; 95% CI = 0.04-0.10, p < .001).

Results suggest that interventions for children with ADHD, and their parents, should begin as soon as possible, ideally prenatally. Developmental sex differences should be considered.

In a cohort of patients with estimated fetal weights (EFWs) <10th centile, we aimed 1) to compare the prevalence of abnormalities of fetal 4-chamber view (4CV) cardiac size, shape, and ventricular contractility in fetal growth restricted (FGR) and small-for-gestational-age (SGA) fetuses and 2) to compare umbilical vein flow (UVF) measurements to standard Doppler surveillance in predicting abnormalities of cardiac function.

Prospective observational cohort study of fetuses with EFW <10th percentile. Measurements of size and shape used were 4CV transverse width, 4CV cardiac area, 4CV global sphericity index, and right-to-left ventricular mid-chamber width ratio. Variables of contractility used were fractional shortening change at the mid-ventricle chamber, global longitudinal strain, fractional area change, and left ventricular cardiac output. The UVF and standard Doppler surveillance including umbilical artery (UA), middle cerebral artery, and cerebroplacental ratio (CPR) were collected. Control data were from previously published studies.

A total of 95 fetuses with EFWs <10th centile were included in the study. The rates of abnormalities of cardiac size and shape and ventricular contractility were all significantly elevated compared with normally grown control fetuses but similar between FGR and SGA fetuses. In a subset of 76 patients with UVF data, evaluation UVF identified more patients with any abnormality of contractility compared with UA (37.9 vs 17.2%, P = .02).

The addition of UVF doubled the detection rate of ventricular contractility abnormalities. The addition of UVF should be considered in the surveillance of FGR and SGA fetuses to further stratify the severity of hypoxemia and to identify those at greater risk for future cardiovascular dysfunction.

This study explores the impact of leisure activity and the association between childhood starvation and the risk of diabetes in older Chinese adults.

Prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort study in China.

A total of 4637 older adults aged ≥65 years, all with documented diabetes history, experiences of childhood starvation, and participation in leisure activities were recruited.

Childhood starvation exposure was assessed via self-reported responses from a structured questionnaire. The leisure activities were measured by 9 distinctive components and categorized into 3 distinct categories: productive activity, recreational activity, and sedentary activity. Diabetes status was determined by self-reported, physician-diagnosed cases during the follow-up period. Nonparametric survival models were employed for analysis.

Over an average follow-up period of 4.3 years, 215 of 4637 participants (4.6%) reported a confirmed diagnosis of diabetes. Nonparametric survival models showed that those reporting childhood starvation had a higher risk of late-life diabetes [hazard ratio (HR) 1.72, 95% CI 1.21-2.44]. Engaging in productive activity (HR 0.90, 95% CI 0.83-0.99) and recreational activity (HR 0.88, 95% CI 0.77-1.00) was linked with a reduced risk of late-life diabetes. Sedentary activity did not show a significant effect. Further analysis highlighted the interactions effects of leisure activities on diabetes risk across different demographic and historical exposure subgroups.

Engaging in productive and recreational leisure activities was inversely associated with the risk of diabetes in older adults who experienced childhood starvation. Promoting such activities could be beneficial in mitigating long-term diabetes risk related to early-life nutritional deficiencies.

The general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood.

We investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [∑DMAP], diethyl [∑DEAP], and total dialkyl phosphate [∑DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations (β and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype.

Carotid intima-media thickness z-score was lower (β: -0.14 [95 % CI: -0.25, -0.02]) and HDL cholesterol z-score was higher (β: 0.14 [95 % CI: 0.02, 0.25]) for increases in ∑DEAP concentrations. Carotid intima-media distensibility z-score was lower (β: -0.08 [95 % CI: -0.19, 0.03]) for increases in ∑DMAP concentrations, and systolic blood pressure z-score was higher (β: 0.10 [95 % CI: -0.01, 0.21]) for increases in ∑DMAP and ∑DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively.

We observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in ∑DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in ∑DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively.

Fetal glucagon concentrations are elevated in the presence of a compromised intrauterine environment, as in cases of placental insufficiency and perinatal acidaemia. Our objective was to investigate the impact of late gestation fetal hyperglucagonaemia on in vivo insulin secretion and pancreatic islet structure. Chronically catheterized late gestation fetal sheep received an intravenous infusion of glucagon at low (5 ng/kg/min; GCG-5) or high (50 ng/kg/min; GCG-50) concentrations or a vehicle control (CON) for 8-10 days. Glucose-stimulated fetal insulin secretion (GSIS) was measured following 3 h (acute response) and 8-10 days (chronic response) of experimental infusions. Insulin, glucose and amino acid concentrations were measured longitudinally. The pancreas was collected at the study end for histology and gene expression analysis. Acute exposure (3 h) to GCG-50 induced a 3-fold increase in basal insulin concentrations with greater GSIS. Meanwhile, chronic exposure to both GCG-5 and GCG-50 decreased basal insulin concentrations 2-fold by day 8-10. Chronic GCG-50 also blunted GSIS at the study end. Fetal amino acid concentrations were decreased within 24 h of GCG-5 and GCG-50, while there were no differences in fetal glucose. Histologically, GCG-5 and GCG-50 had lower β- and α-cell proliferation, as well as lower α-cell mass and pancreas weight, while GCG-50 had lower islet area. This study demonstrates that chronic glucagon elevation in late gestation fetuses impairs β-cell proliferation and insulin secretion, which has the potential to contribute to later-life diabetes risk. We speculate that the action of glucagon in lower circulating fetal amino acid concentrations may have a suppressive effect on insulin secretion. KEY POINTS: We have previously demonstrated in a chronically catheterized fetal sheep model that experimentally elevated glucagon in the fetus impairs placental function, reduces fetal protein accretion and lowers fetal weight. In the present study, we further characterized the effects of elevated fetal glucagon on fetal physiology with a focus on pancreatic development and β-cell function. We show that experimentally elevated fetal glucagon results in lower β- and α-cell proliferation, as well as decreased insulin secretion after 8-10 days of glucagon infusion. These results have important implications for β-cell reserve and later-life predisposition to diabetes.

Malnutrition early in life increases the later-life risk of noncommunicable diseases, and previous epidemiologic studies have found a link between famine and renal impairment, but no consensus has been reached. This meta-analysis and systematic review were conducted to assess the correlation between early-life famine exposure and the risk of developing renal impairment. Search in Embase, Scopus, Web of Science, PubMed, and Cochrane using keywords that report the correlation between early famine exposure and renal function indicators. RevMan and Stata software were used for data analysis. This meta-analysis contained twelve observational studies. The findings demonstrated a link between prenatal famine exposure and a higher risk of developing chronic kidney disease (CKD) (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.25, 2.39), a decreased estimated glomerular filtration rate (eGFR) (mean difference (MD) = -10.05, 95% CI: -11.64, -8.46), and increased serum creatinine (Scr) (MD = 0.02, 95% CI: 0.01, 0.03) compared to unexposed individuals. Famine exposure in childhood was associated with decreased eGFR (MD = -9.43, 95% CI: -12.01, -6.84) and increased Scr (MD = 0.03, 95% CI: 0.01, 0.04), but not with CKD (OR = 0.980, 95% CI: 0.53, 1.81). Famine exposure in adolescence and adulthood was associated with decreased eGFR (MD = -20.73, 95% CI: -22.40, -19.06). Evidence certainty was deemed to be of low or extremely low quality. Famine exposure early in life could pose a greater risk of developing renal impairment in adulthood, but this outcome may be driven by uncontrolled age differences between famine-births and post-famine-births (unexposed).

Chronic kidney disease (CKD) is a widespread condition often resulting from multiple factors, including maternal influences. These risk factors not only heighten the likelihood of developing CKD but increase the risk of a preterm birth. Adverse events during nephrogenesis can disrupt kidney development, leading to a reduced number of nephrons. As survival rates for preterm infants improve, more individuals are living into adulthood, thereby elevating their risk of CKD later in life. This review aims to explore the connections between preterm birth, kidney development, and the increased risk of CKD, while proposing practical solutions for the future through a multidisciplinary approach. We examine human studies linking preterm birth to negative kidney outcomes, summarize animal models demonstrating kidney programming and reduced nephron numbers, and consolidate knowledge on common mechanisms driving kidney programming. Additionally, we discuss factors in the postnatal care environment that may act as secondary insults contributing to CKD risk, such as acute kidney injury (AKI), the use of nephrotoxic drugs, preterm nutrition, and catch-up growth. Finally, we outline recommendations for action, emphasizing the importance of avoiding modifiable risk factors and implementing early CKD screening for children born preterm. Together, we can ensure that advancements in kidney health keep pace with improvements in preterm care.

To ascertain whether maternal food insecurity was associated with low birth weight of their babies.

Systematic review conducted following the items of the Preferred Reporting Items for Systematic Reviews-PRISMA, and recorded in PROSPERO. The descriptors food security, low birth weight and infant low birth weight were combined in the electronic databases: Scopus, PubMed, Cochrane Library, Latin American and Caribbean Health Sciences Literature and Google Scholar, independently by two researchers, between October 2022 and September 2023. The meta-analysis of the association between food insecurity and low birth weight was conducted. The included studies underwent quality and risk of bias assessment.

The initial search resulted in 631 records, 12 of which met the inclusion criteria and were selected for this study. Mothers experiencing food insecurity presented 3.09 more risk of having low birth weight babies when compared to those in food security situations.

Evaluating and monitoring the food and nutritional situation of pregnant women is necessary, with emphasis on the importance of prenatal care, to direct public policies that ensure food security and strengthen adequate nutritional conditions for pregnant women and their babies.

Insufficient evidence regarding how maternal undernutrition affects craniofacial bone development persists. With its unique focus on the impact of gestational protein restriction on calvaria and mandible osteogenesis, this study aims to fill, at least in part, this gap. Female mice were mated and randomized into NP (normal protein) or LP (low protein) groups. On the 18th gestational day (GD), male embryos were collected and submitted to microtomography (µCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), PCR, and autophagy dynamic analyses. The study shows that the LP offspring exhibited lower body mass than the NP group, with µCT analysis revealing no volumetric differences in fetus's head. EDS analysis showed lower calcium and higher phosphorus percentages in mandibles and calvaria. SEM assessment evidenced higher hydroxyapatite crystal-like (HC) deposition on the calvaria surface in LP fetus. Conversely, lower HC deposition was observed on the mandible surface, suggesting delayed matrix mineralization in LP fetuses with a higher percentage of collagen fibers in the mandible bone. The autophagy process was reduced in the mesenchyme of LP fetuses. PCR array analysis of 84 genes revealed 27 genes with differential expression in the LP progeny-moreover, increased mRNA levels of Akt1, Mtor, Nfkb, and Smad1 in the LP offspring. In conclusion, the results suggest that gestational protein restriction anticipated bone differentiation in utero, before 18GD, where this process is reduced compared to the control, leading to the reduction in bone area at 15 postnatal day previously observed. These findings provide insights into the molecular and cellular mechanisms of mandible development and suggest potential implications for the Developmental Origins of Health and Disease (DOHaD).

In this study, we aimed to assess the associations between early exposure to famine and the risks of diabetic complications in adult patients with type two diabetes.

The participants in this study were selected from China National HbA1c Surveillance System (2009-13) and further stratified according to the birth year. The participants born between 1956-59, 1959-61, and 1962-64 were classified as foetal exposed group with 70 852, infant/toddler exposed group with 93 616, and unexposed group with 72 723 participants. The association between exposure to famine in early life and risks of diabetic complications were analysed by logistic regression. We assessed the attributing effects of the interaction between exposure to famine in early life and modifiable risk factors by the multiplicative and additive interactive models.

After adjustments for sex, famine severity, economic status in adulthood, body mass index, blood pressure, low-density lipoprotein cholesterol, glycated haemoglobin, diabetes duration, and the use of antidiabetic agents, the increased risks of coronary heart disease (odds ratio (OR) = 1.31; 95% CI (confidence interval) = 1.26, 1.36), cerebrovascular disease (OR = 1.32; 95% CI = 1.24, 1.41), and diabetic retinopathy (OR = 1.06; 95% CI = 1.02, 1.10) were observed in patients with early-life exposure to famine. The reduced risk of diabetic kidney disease (OR = 0.94; 95% CI = 0.90, 0.99) was observed in patients with early-life exposure to famine compared with those without famine exposure. The interaction analyses indicated that obesity might exacerbate the increased risk of coronary heart disease (OR = 1.26; 95% CI = 1.22, 1.30), cerebrovascular disease (OR = 1.26; 95% CI = 1.21, 1.32), and diabetic retinopathy associated with early-life exposure to famine (OR = 1.09; 95% CI = 1.06, 1.12) in patients with type two diabetes. Moreover, high economic status in adulthood might also exacerbate the increased risk of coronary heart disease (OR = 1.35; 95% CI = 1.30, 1.40) and cerebrovascular disease (OR = 1.33; 95% CI = 1.23, 1.43) associated with early-life exposure to famine in patients with type two diabetes.

Early-life exposure to famine in patients with type two diabetes might be associated with increased risks of coronary heart disease, cerebrovascular disease, and diabetic retinopathy but a reduced risk of diabetic kidney disease in adulthood. Obesity and high economic status might further exacerbate the risk of diabetic complications associated with early-life exposure to famine. Improving early-life nutritional status may promote better risk prevention and management of diabetic complications in patients with type two diabetes.

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.