Search Results (240)

Background/Objectives: We aimed to identify eating habits associated with hepatic fat fraction (HFF) and assess effect modification by an established genetic variant for fatty liver disease, PNPLA3 rs738409, among 381 general-risk adolescents. Methods: Dietary intake was assessed using the Block Kids Food Frequency Questionnaire and HFF was measured via magnetic resonance imaging (MRI) at age ~16 years. We first characterized naturally occurring dietary patterns using principal component analysis followed by reduced-rank regression with HFF as the response variable to identify a dietary pattern that is both relevant to the population and associated with HFF. Next, we investigated associations of the dietary pattern with HFF using linear regression models that accounted for maternal gestational diabetes, education, and prenatal smoking and child sex, age, Tanner stage, and BMI. Finally, we tested for a dietary pattern and PNPLA3 rs738409 interaction and stratified by genotype if P-interaction < 0.05. Results: The participants were 16.7 ± 1.2 years (range: 12.6–19.6 years). Half were female (50.4%) and 52.0% identified as non-Hispanic White. The dietary pattern of interest was composed of vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef, and was inversely associated with HFF (−0.48 [95% CI: −0.81, −0.16]). Stratified analyses revealed the strongest inverse association observed between the diet pattern score and HFF in the high-risk-variant (GG) group (−2.19 [−4.35, −0.03]), followed by the intermediate-risk (CG) group (−0.43 [−0.77, −0.10]), but not the low-risk (CC) group (−0.32 [−0.77, 0.13]). Conclusions: A diet high in vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef—potentially capturing an active, on-the-go lifestyle—is associated with lower HFF during adolescence, especially among individuals at genetic risk. Full article

The first 1000 days of life, starting from conception to a child’s second birthday, constitute a pivotal period for fetal lung and pulmonary vascular development. Maternal nutrition during this period plays an important role in fetal growth, immune programming and organ development, including that of the pulmonary system. This narrative review consolidates evidence linking maternal nutrition and early-life nutrient intake during this period with the development of pulmonary hypertension in the newborn. We examine the influence of both nutrient deficiencies and excesses on fetal lung and vascular development. We performed a structured search of PubMed and Embase (conducted from February 2025 to March 2025) and screened reference lists. Twenty-eight peer-reviewed studies were included, comprising human clinical and observational evidence and studies on animal models. The findings suggest that imbalances in maternal diet can disrupt placental function, induce inflammation, and trigger epigenetic alterations, all contributing to pulmonary vascular dysfunction and increased pulmonary hypertension susceptibility in neonates. Notably, maternal undernutrition and thiamine deficiency during lactation have been directly linked to pulmonary hypertension in infants. Conversely, high-fat diets and excessive polyphenol intake have been associated with adverse fetal cardiovascular remodeling. While current evidence is primarily derived from animal models and observational studies, it highlights the urgent need for targeted nutritional strategies and clinical trials during pregnancy. Although human causality is unproven for most exposures, studying maternal nutrition in the first 1000 days could offer a cost-effective method for reducing the burden of pediatric pulmonary hypertension and its long-term consequences and for prospective trials aimed at preventing early-life pulmonary vascular disease. Full article

Objective: This study aimed to explore how maternal gestational diabetes mellitus (GDM) affects adipose tissue remodeling and the expression of C1q/TNF-related protein 6 (CTRP6) in offspring, with a focus on sex- and depot-specific differences. Methods: A GDM mouse model was established by feeding female C57BL/6J mice a high-fat diet (HFD) before and during pregnancy. Offspring were weaned onto standard chow or an HFD until 9 weeks of age. Metabolic phenotypes, adipose tissue morphology, and CTRP6 expression were assessed at weaning and adulthood. Results: GDM offspring exhibited increased adiposity and impaired glucose tolerance at weaning, with these effects persisting into adulthood in males. Maternal GDM reduced plasma CTRP6 levels in both sexes at weaning, but in adulthood, male GDM offspring maintained lower circulating CTRP6, while females on the chow diet showed elevated levels. Tissue-specific analysis revealed decreased CTRP6 expression in male interscapular brown adipose tissue (iBAT) and female visceral white adipose tissue (vWAT), accompanied by depot- and sex-specific changes in adiponectin signaling. Conclusions: Maternal GDM programs offspring’s metabolic phenotype and adipose tissue CTRP6 expression in a sex- and depot-specific manner, suggesting CTRP6 may serve as an early, sex-biased indicator of the intergenerational transmission of metabolic disease risk. Full article

Background: The increasing prevalence of low-birth-weight (LBW) offspring from obese mothers underscores the need for dietary strategies to mitigate the transgenerational propagation of metabolic diseases. Objectives: We determined whether dietary protein restriction under obesogenic conditions altered maternal energy balance and led to LBW offspring and whether branched-chain amino acid (BCAA) supplementation improved maternal energy balance and mitigated weight and craniofacial skeletal deficits in offspring. Methods: High-fat-fed obese pregnant Sprague Dawley rats (~8–10 weeks of age, n = 8–11/group) were randomized in study 1 to control high-fat diet (20% protein; HFD), low-protein diet (LP; 5% protein), and LP + BCAA diet (100% BCAA requirements) and in study 2 to control HFD (20% protein), LP (10% protein), and LP + 2BCAA diet (200% BCAA requirements). Post-weaning offspring were fed HFD until 8 weeks of age. Results: Protein restriction promoted hyperphagia and energy expenditure, whereas BCAA supplementation attenuated such hyperphagic effects in pregnancy but not in lactation. Protein restriction reduced maternal body weight in lactation, and although BCAA supplementation did not reverse the weight loss, it enhanced insulin sensitivity and paradoxically reduced offspring survival. Maternal protein restriction reduced offspring body weight and craniofacial bone growth that persisted into adulthood, but BCAA supplementation did not rescue such deficits. Conclusions: Maternal protein restriction in obese dams enhanced maternal energy expenditure but impaired offspring growth and development. Although BCAA supplementation improved maternal energy balance, it was insufficient to reverse the adverse effects of maternal protein restriction on offspring growth under obesogenic conditions. Full article

Background/Objectives: Gestational exposure to a high-fat diet (HFD) reprograms hypothalamic orexigenic circuits prenatally. However, whether astrocytes, critical modulators of this system, are also imprinted by HFD in the fetal brain remains unknown. We investigated the impact of HFD on the prenatal neuroglial architecture of the lateral hypothalamic area (LHA). Methods: Female Wistar rats were fed a control or a 60% fat diet for 12 weeks. Upon reaching obesity (Lee index ≥ 310), dams were mated. Fetuses were harvested via cesarean section at term, and their brains were processed for immunohistochemistry and morphometry to assess cell proliferation, orexin neuron density, and astrocytic reactivity in the LHA. Results: HFD significantly increased cell proliferation and orexinergic neuron density, and induced early signs of astrocyte reactivity in the fetal LHA. These findings reveal that both neuronal and glial components of the LHA orexigenic axis are structurally reprogrammed before birth. Conclusions: This study provides the first evidence that HFD simultaneously alters neuronal and glial developmental trajectories in the fetal hypothalamus. The concurrent programming of astrocytes and orexigenic neurons suggests a prenatal origin for neuroinflammatory susceptibility, reframing obesity as a neurodevelopmental disorder shaped by early life nutritional environments. Full article

Background: The placenta stands at the maternal–fetal interface and is a key organ regulating the intrauterine environment. In pregnancies exposed to obesity, placental function, signaling, and nutrient handling are adversely altered. Pre-conception weight loss is a potential intervention to alter an obesogenic milieu of pregnancy, which we investigated in a mouse model of maternal obesity using diet or administration of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Methods: Pre-pregnancy weight loss in C57BL/6 high-fat diet (HFD)-fed dams was induced in the pre-pregnancy period by switching diet from HFD to chow diet or administering liraglutide (0.3 mg/kg/day subcutaneously for 4 weeks) whilst continuing HFD. In addition, a group of HFD-fed dams were switched to chow diet post-conception. The metabolomic profile and gene expression within the placenta was compared at day 18–20 of gestation. Results: ¹H NMR spectroscopy metabolomic analysis of placenta of HFD mice showed an altered amino acid metabolomic profile, with lower aspartate, glutamate, and glutamine levels compared to the placenta of chow-fed mice (p < 0.05). Meanwhile, gene expression analysis identified both oxidative stress and inflammation in the placentas of HFD-fed dams. Whilst dietary modification alone was sufficient to reduce markers of oxidative stress and inflammation, liraglutide treatment modulated pathological changes, including placental metabolic stress but not inflammation. Conclusions: These findings highlight the importance of dietary or pharmacological interventions in the pre- or immediate post-conception period, with pre-conception offering a critical window to reduce aberrant placental changes induced by obesity. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in both children and adults. Pediatric MASLD, however, is not simply an early form of adult disease, as it exhibits distinct developmental, histological, and metabolic features. Emerging evidence suggests that these characteristics arise from a complex, multi-hit continuum that begins in utero. Maternal obesity, gestational diabetes, and poor diet quality during pregnancy have been associated with greater hepatic steatosis in offspring, raising the possibility that intrauterine exposure to dyslipidemia, hyperglycemia, and elevated free fatty acid flux may contribute to early hepatic lipid deposition. After birth, feeding behaviors such as a prolonged breastfeeding appear protective, whereas formula feeding, especially high added-sugar formulations, may accelerate rapid weight gain and increase susceptibility to later steatosis. Early childhood diets high in added sugars, saturated fats, and ultra-processed foods may further promote hepatic lipogenesis and inflammation and interact with underlying genetic susceptibility. Given the heterogeneity of available human cohort studies and mechanistic model systems, this narrative review summarizes converging evidence from prenatal, postnatal, and early childhood nutritional exposures and their relationship to offspring hepatic lipid accumulation, emphasizing early-life windows for intervention to reduce the burden of pediatric MASLD. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a common pregnancy complication, and maternal diet before conception may be an important modifiable risk factor. This study aimed to investigate the association between maternal pre-pregnancy energy and macronutrient intake and the risk of GDM. Methods: Data from the BORN2020 cohort in Northern Greece were used. Women were recruited at their first trimester prenatal visit (11–13 weeks of gestation) and provided detailed dietary data via a validated food frequency questionnaire (FFQ), reflecting intake in the six months prior to conception. Weighted Quantile Sum (WQS) regression models were applied to assess the joint effects of food-derived macronutrient mixtures on GDM risk. Analyses were adjusted for parity, maternal age, pre-pregnancy BMI, thyroid disorders, smoking, energy intake, and physical activity. Results: In total, 797 women were included in the analyses. In normal-BMI women, higher pre-pregnancy intake of energy (aOR = 81.16, 95% CI: 4.55–1447.46), total carbohydrates (aOR = 50.66, 95% CI: 3.59–715.04), total fat (aOR = 9.35, 95% CI: 1.17–74.54), and total protein (aOR = 11.06, 95% CI: 1.14–107.09) were significantly associated with increased odds of GDM. The main contributing foods were energy-dense and processed items such as puff pastry, processed meats, potatoes, refined grains, and dairy products. In contrast, dietary fiber, vegetable protein, and animal protein were not significantly associated with GDM risk. Among overweight and obese women, none of the macronutrient or energy mixtures showed significant associations. Conclusions: For women of normal weight, a pre-conception diet high in energy and macronutrients from processed foods is a significant predictor of GDM risk. This association was not found in overweight or obese women, highlighting a critical window for targeted nutritional intervention for normal-weight individuals before pregnancy. Full article

Background: Maternal diet quality during pregnancy may significantly influence fetal growth and birth weight. Objectives: This study aimed to assess the dietary quality of pregnant women in Korea and investigate its association with the risk of delivering a small-for-gestational-age (SGA) infant. Methods: A total of 1158 pregnant women and their newborns were recruited from the Mothers and Children’s Environmental Health (MOCEH) 2006–2010 cohort. Maternal dietary intake during gestational weeks 12–28 was assessed using a validated food frequency questionnaire. The nutrient adequacy ratio (NAR), mean adequacy ratio (MAR), and Korean Healthy Eating Index (KHEI) were employed to evaluate dietary quality. Birth outcomes were obtained from hospital records, and logistic regression analyses were performed to examine associations between maternal dietary quality and SGA risk. Results: Higher KHEI scores were significantly associated with increased nutrient intake, with the exception of fat, and demonstrated a positive association with the NAR of 15 nutrients. After adjusting for covariates, women in the highest KHEI quartile exhibited a significantly lower risk of SGA birth than those in the lowest quartile (adjusted odds ratio: 0.448; 95% confidence interval: 0.201–0.997; P-for-trend = 0.031). Conclusions: Enhanced maternal diet quality, as measured using the KHEI, is associated with improved nutrient intake and a reduced risk of SGA births among Korean pregnant women. These findings underscore the need for public health strategies that promote high-quality diets during pregnancy to improve birth outcomes. Full article

Cardiovascular–kidney–metabolic syndrome (CKMS) encompasses interconnected cardiovascular, renal, and metabolic disorders, including obesity, hypertension, and type 2 diabetes. Oxidative stress is increasingly recognized as a central driver of this multi-organ dysfunction. Among maternal influences, exposure to a high-fat diet (HFD) during pregnancy and lactation consistently predisposes offspring to CKMS-related phenotypes in animal models. While oxidative stress is implicated as a key mediator, its precise role in developmental programming remains unclear, and comparing the differences in its role between overt CKMS and CKM programming is critical. Critical gaps include whether oxidative stress acts uniformly or in an organ- and time-specific manner, which signals initiate long-term redox alterations, and whether these effects are reversible. Furthermore, its interactions with other programming pathways—such as renin–angiotensin system activation, epigenetic dysregulation, gut microbiota imbalance, and altered nutrient sensing—remain insufficiently explored. This review uniquely highlights maternal HFD-induced oxidative stress as a mechanistic axis of CKMS programming and delineates unresolved questions that limit translation. By integrating evidence across organ systems and proposing priorities for multi-organ profiling, refined models, and longitudinal human studies, we outline a forward-looking agenda for the field. Ultimately, clarifying how maternal HFD and oxidative stress shape offspring CKMS risk is essential to inform targeted antioxidant strategies to reduce the intergenerational transmission of CKMS risk. Full article

This review explores the maternal gut microbiome’s role in shaping neonatal neurodevelopmental outcomes following perinatal asphyxia (PA), a leading cause of infant mortality and disability with limited therapeutic options beyond hypothermia. We synthesized current evidence on microbiome-mediated neuroprotective mechanisms against hypoxic-ischemic brain injury. The maternal microbiome influences fetal development through bioactive metabolites (short-chain fatty acids, indole derivatives) that cross the placental barrier, bacterial antigen regulation, and infant microbiome colonization. These pathways activate multiple protective mechanisms: anti-inflammatory signaling via NF-κB suppression and regulatory T cell expansion; antioxidant defenses through Nrf2 activation; neural repair via BDNF upregulation and neurogenesis; and oxytocin system modulation. Animal models demonstrate that maternal dysbiosis from high-fat diet or antibiotics exacerbates PA-induced brain damage, increasing inflammatory markers and hippocampal injury. Conversely, probiotic supplementation, dietary fiber, and specific interventions (omega-3, resveratrol) reduce neuroinflammation and oxidative injury. Human studies link maternal dysbiosis-associated conditions (obesity, gestational diabetes) with adverse pregnancy outcomes, though direct clinical evidence for PA severity remains limited. Understanding the maternal microbiome-fetal brain axis opens therapeutic avenues, including prenatal probiotics, dietary modifications, and targeted metabolite supplementation to prevent or mitigate PA-related neurological sequelae, potentially complementing existing neuroprotective strategies. Full article

Background: The fetal period is critical for neurodevelopment, with maternal diet emerging as a key environmental factor influencing long-term child health. This study investigated the associations between maternal dietary patterns during pregnancy and neurocognitive and behavioral outcomes in 4-year-old children, with a particular focus on sex-related differences. Methods: We used data from the Piccolipiù Italian birth cohort, including 2006 mother/child pairs. Maternal dietary intake during pregnancy was assessed via a questionnaire and categorized into distinct patterns using Principal Component Analysis (PCA). Child neurodevelopment was evaluated at age 4 using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and the Child Behavior Checklist (CBCL 1.5–5). Linear and logistic regression models were employed, adjusting for potential confounders and stratifying by child sex. Results: Two major maternal dietary patterns were identified: “Processed and high-fat foods” and “Fresh foods and fish”. Higher maternal adherence to the “Processed and high-fat foods” pattern was associated with increased externalizing behaviors in offspring (β = 0.88; 95%CI 0.28–1.49; p = 0.004). In males, this pattern was associated with an increased clinical risk of Attention Deficit Hyperactivity Disorder (ADHD) (OR (Odds Ratio) = 1.13; 95%CI: 1.02–1.26; p = 0.021). Conclusions: Our findings indicate that maternal consumption of a diet rich in processed and high-fat foods during pregnancy is associated with increased behavioral problems in children, with sex-specific vulnerabilities: slightly higher externalizing behaviors in girls and an increased risk of ADHD in boys. These results underscore the importance of promoting healthy maternal dietary patterns during pregnancy as a targeted early prevention strategy for supporting child neurodevelopment. Full article

Background/Objectives: Maternal nutrition and pregestational BMI are critical determinants of pregnancy outcomes. This prospective multicenter observational study investigated the interplay between prepregnancy BMI, dietary patterns, and oxidative/inflammatory status in 153 Italian healthy pregnant women with normal weight (NW), overweight (OW), or obesity (OB). Methods: Detailed clinical, biochemical, placental, and neonatal data were measured at third trimester and delivery. Dietary intake was assessed via a validated questionnaire, and dietary patterns were derived using principal component analysis. Results: OW and OB women had significantly higher levels of inflammatory (CRP, hepcidin) and oxidative stress biomarkers (DNA/RNA damage, catalase activity) than NW. Multivariate models confirmed independent associations between BMI and these biomarkers (CRP: β = 0.297, p = 0.000; hepcidin: β = 1.419, p = 0.006; DNA/RNA damage: β = 409.9, p = 0.000; catalase activity: β = 1.536, p = 0.000). Superoxide dismutase activity and total antioxidant capacity were not associated with BMI. Nutritional intake across BMI groups was largely suboptimal relative to national recommendations, with insufficient levels of polyunsaturated fats and key micronutrients. Four dietary patterns were identified, with adherence varying by BMI. A “prudent-style” pattern (high plant, low animal) was positively associated with gestational age (β = 0.243, p = 0.033) and inversely with neonatal head circumference (β = −0.414, p = 0.050). A “Western-like” pattern (high sugars, snacks, animal fats) was linked to reduced maternal ferritin (β = −2.093, p = 0.036) and increased neonatal head circumference (β = 0.403, p = 0.036). However, not all deviations from the “prudent-style” pattern were metabolically equivalent: while Pattern 3 (high-protein, carbohydrate) may offer partial protective effects, Pattern 4 (moderate protein/plant/sugar) displayed elements of nutritional imbalance with signs of placental inefficiency (β = −0.384, p = 0.023). Conclusions: These findings underscore the dual impact of maternal BMI and diet quality on oxidative-inflammatory balance and perinatal outcomes, supporting the need for early, individualized nutritional strategies in pregnancy. This is further emphasized by the variability in dietary adherence across BMI categories. Full article

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity. We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes. These phenotypes were absent in female offspring and those exposed only during gestation. Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding. This pattern was specific to mice with ASD-like behaviors. Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk. Full article