Journal of Developmental Origins of Health and Disease最新文献

It is known that adverse stimuli, such as altered diets during pregnancy and lactation, can result in deleterious effects on the progeny. The aim of this study was to evaluate the possible gastrointestinal repercussions in the offspring of Wistar rats exposed to high-fat diets. Pregnant rats were divided into three groups: normolipidic diet (3.5% lipids), a diet containing 28% lipids, and a diet with 40% lipids. Body weight and food, water, daily caloric, and macronutrient intake were evaluated in the pregnant rats. Structural and functional gastrointestinal parameters were assessed in 30-day-old male pups. Depending on the lipid content of the maternal diet, the pups may exhibit gastric mucosal thickening, an increase in the relative weight of the small intestine, a reduction in the jejunal and ileal mucosa, and a decrease in the total thickness of the ileum. Additionally, there may be a reduction in the number of villi per area in these organs and a thinning of the muscular layer in the large intestine. The structural changes induced by the maternal high-fat diet seem to reduce the stomach's sensitivity to ethanol-induced ulcers, which is the only functional alteration observed. Therefore, the offspring of dams exposed to high-fat diets during pregnancy and lactation exhibits impaired gastrointestinal development, with alterations depending on dietary fat content and specific gastrointestinal regions. Structural changes did not always result in functional abnormalities and, in some cases, appeared protective. The long-term consequences of the observed morphological alterations require further investigation.

Household income and caregiver mental health are important drivers of children's health and development. The COVID-19 pandemic created huge economic and mental health disruptions. This study examines financial hardship and its relationship with caregiver and child mental health using Australia's only representative data spanning three years of the pandemic. Analysis of the repeated, cross-sectional National Child Health Poll included 12,408 caregivers and 20,339 children over six waves (June 2020-April 2023). Caregivers reported their income (dichotomised into low versus not) and deprivation (missing one or more of eight essential items, versus not) and mental health for themselves (Kessler-6, poor versus not) and each child (Self-Rated Mental Health, poor/fair versus good/very good/excellent). Binary logistic models were fitted to predict marginal probabilities of mental health measures by low income and deprivation, over time. Results show that while low income decreased from 41% to 34% over the study period, deprivation increased from 30% to 35%. Poor mental health peaked with stay-at-home orders in 2021 before recovering. Caregivers experiencing low income or deprivation had higher rates of poor mental health throughout the study and slower recovery compared to those without financial hardship. Children in families experiencing financial hardship had slightly higher proportions of poor/fair mental health in 2021-2022, but they were mostly equivalent in June 2020 and April 2023 (range 6-8%). Addressing financial hardship may offer an avenue for improving caregiver mental health. This has implications for post-pandemic recovery and addressing contemporary issues of increasing cost of living and limited mental health supports and services.

Prenatal alcohol exposure (PAE) is associated with cognitive, behavioural, and developmental impairments throughout the lifespan of affected individuals, but there is limited evidence on how early this impact can be identified through routinely collected childhood data. This paper explores the relationship between PAE and the Early Years Foundation Stage Profile (EYFSP), a statutory teacher-based summative assessment of early development in relation to learning goals. This analysis uses the Born in Bradford dataset, a UK based cohort (n = 13,959; full dataset), which collected self-reported PAE from 11,905 mothers, with 19.8% reporting drinking alcohol at some point during pregnancy. Coarsened exact matching was conducted to examine relationships between patterns of PAE and children achieving a 'Good Level of Development' on the EYFSP, a binary variable assessed at 4-5 years of age, controlling for known confounders, including deprivation, mother's education, exposure to other teratogenic substances, and child's age at assessment. Additionally, we examined EYFSP sub-scores to identify specific developmental deficits associated with PAE.The key finding is a statistically significant association between PAE at a level of consuming 5 or more units of alcohol (equivalent to 50 ml or 40 g of pure alcohol) at least once per week from the 4^th month of pregnancy onwards and lower EYFSP scores when accounting for established confounding variables. These findings highlight that the detrimental impact of alcohol during pregnancy can be identified using statutory educational assessments. This has implications internationally for prevention work, policy, and commissioning of support services for people impacted by PAE.

Nutrition is the critical nongenetic factor that has a major influence on the health status of an organism. The nutritional status of the mother during gestation and lactation plays a vital role in defining the offspring's health. Undernutrition during these critical periods may induce chronic metabolic disorders like obesity and cardiovascular diseases in mothers as well as in offspring. The present study aims to evaluate the impact of undernutrition during gestational and lactational periods on the plasma metabolic profile of dams. Additionally, we investigated the potential synergistic mitigating effects of astaxanthin and docosahexaenoic acid (DHA) on dysregulated plasma metabolic profiles. Evaluation of plasma lipid profile revealed that undernourishment resulted in elevated levels of total cholesterol, triglycerides, low density and very low-density lipoproteins in dams. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomics illustrated that pathways related to lipid metabolism, such as cholesterol metabolism, steroid biosynthesis and metabolism of amine-derived hormones, were dysregulated by undernourishment. Additionally, pathway enrichment analysis predicted that there is a high incidence of development of desmosterolosis, hypercholesterolaemia, lysosomal acid lipase deficiency and Smith-Lemli-Opitz syndrome in the offspring, reflecting predisposition in mothers. However, synergistic supplementation of astaxanthin and DHA ameliorated these adverse effects by regulating a separate set of metabolic pathways associated with lipid metabolism. They included branched chain amino acid degradation such as valine, leucine and isoleucine, metabolism of alpha-linolenic acid, lipoic acid, lysine degradation, biosynthesis, elongation and degradation of fatty acids.

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.

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.

This study examined associations between pregnancy and infant birth outcomes with child telomere length at age 17 years; and investigated if there are sex differences between pregnancy complications and telomere length. We utilised the population-based prospective Raine cohort study in Western Australia, Australia. 2900 pregnant women were recruited at 16-20 weeks' gestation (Gen 1), and their children (Gen 2) were followed up over several years. Generalised linear models were used to examine relationships between pregnancy or birth outcomes (gestational diabetes, pre-eclampsia, preterm birth, low birth weight, macrosomia), and as a composite, with telomere length, measured via a DNA sample from blood at 17 years of age. Analyses were adjusted for a range of confounders. Among the 1202 included children, there were no differences in child telomere length for any of the individual maternal or birth weight pregnancy outcomes nor were there any significant interactions between each of the complications (individual or composite) and the sex of the child. However, females born from any of the 5 adverse outcomes had shorter telomeres (estimated mean (SE) = -0.159 (0.061), p = 0.010) than females born in the absence of these complications. Specifically, females born from a pre-eclamptic pregnancy had shorter telomeres than females not born from a pre-eclamptic pregnancy (estimated mean (SE) = -0.166 (0.072), p = 0.022). No relationships were observed in males. Further longitudinal studies are needed to understand mediating factors that are important in predicting offspring telomere length and the necessity to investigate females and males independently.

Paternal exposures (and other non-maternal factors) around pregnancy could have important effects on offspring health. One challenge is that data on partners are usually from a subgroup of mothers with data, potentially introducing selection bias, limiting generalisability of findings. We aimed to investigate the potential for selection bias in studies using partner data.We characterise availability of data on father/partner and mother health behaviours (smoking, alcohol, caffeine and physical activity) around pregnancy from three UK cohort studies: the Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford and the Millennium Cohort Study. We assess the extent of sample selection by comparing characteristics of families where fathers/partners do and do not participate. Using the association of parental smoking during pregnancy and child birthweight as an example, we perform simulations to investigate the extent to which missing father/partner data may induce bias in analyses conducted only in families with participating fathers/partners.In all cohorts, father/partner data were less detailed and collected at fewer timepoints than mothers. Partners with a lower socio-economic position were less likely to participate. In simulations based on ALSPAC data, there was little evidence of selection bias in associations of maternal smoking with birthweight, and bias for father/partner smoking was relatively small. Missing partner data can induce selection bias. In our example analyses of the effect of parental smoking on offspring birthweight, the bias had a relatively small impact. In practice, the impact of selection bias will depend on both the analysis model and the selection mechanism.

Protein malnutrition during critical periods poses significant risks to reproductive health. Thus, this study aims to evaluate the immediate and delayed effects of a 30-day low-protein diet on the postnatal development of the male reproductive system. For so, male rats were fed a protein-deficient diet from postnatal day 30-60, followed by evaluations of testis, epididymis, and spermatozoa both at the end of the diet and after a 60-day recovery period. Testicular and epididymal weight was lowered in pubertal animals. Several histological alterations were found in the testis, such as acidophilic cells and vacuoles in the seminiferous epithelium, and sperm production was compromised. In the epididymis, the luminal compartment was diminished, and the stroma was enlarged both in the caput and cauda; in the cauda, the epithelial compartment was enlarged; the transit time of spermatozoa through this organ was diminished. Testosterone production was lowered. Spermatozoa's motility, mitochondrial activation, and acrosomal integrity were impaired, and several alterations in morphology were observed. After the recovery period, testicular and epididymal weight was restored. Tissue remodulation was observed in the epididymis, but the spermatozoa's transit time in this organ was not altered. Sperm and testosterone production, spermatozoa motility, mitochondrial activation, and acrosomal integrity were also restored. However, testicular histological alterations and spermatic morphological abnormalities were maintained in protein-restricted animals. Protein restriction during peripuberty impairs the reproductive maturation of pubertal Wistar rats, impairing testicular and epididymal function, with lasting effects even after dietary correction.

Reducing inequalities in preconception health and care is critical to improving the health and life chances of current and future generations. A hybrid workshop was held at the 2023 UK Preconception Early and Mid-Career Researchers (EMCR) Network conference to co-develop recommendations on ways to address inequalities in preconception health and care. The workshop engaged multi-disciplinary professionals across diverse career stages and people with lived experience (total n = 69). Interactive discussions explored barriers to achieving optimal preconception health, driving influences of inequalities and recommendations. The Socio-Ecological Model framed the identified themes, with recommendations structured at interpersonal (e.g. community engagement), institutional (e.g. integration of preconception care within existing services) and environmental/societal levels (e.g. education in schools). The co-developed recommendations provide a framework for addressing inequalities in preconception health, emphasising the importance of a whole-systems approach. Further research and evidence-based interventions are now needed to advance the advocacy and implementation of our recommendations.