Journal of Developmental Origins of Health and Disease最新文献

Brain development and face morphology are related through underlying biological mechanisms, namely embryonic neuroectodermal processes. This study examined whether the facial parameters identified in children can help understand the neurodevelopmental impact of prenatal exposures on child behavior. We studied 9- to 10-year-old children of European descent from Generation R Study (N = 2,779) with three-dimensional face photographs. With an AI model of a 3D graph autoencoder, each facial shape was compressed into 200 traits representing facial morphology. We examined associations of traits with internalizing and externalizing behaviors and attention problems. Next, select prenatal substance and micronutrient exposures were related to facial traits using adjusted linear regression analyses. We identified a robust association between one specific facial trait and attention problem scores (β = -1.47, p = 0.038). This trait features chin retrusion, mild nasal contour variation, nose tip protrusion, and overall facial asymmetry. Higher prenatal vitamin D and folic acid concentrations were associated with more facial curvature (β = 0.0001, 95%CI: 0.00001 to 0.0002, p = 0.002; and β = 0.0003, 95%CI: 0.00002 to 0.0005, p = 0.03 accordingly), while prenatal tobacco smoking showed a negative association both until the mother became aware of pregnancy (β = -0.008, 95%CI: -0.0135 to -0.0014, p = 0.02) and throughout pregnancy (β = -0.006, 95%CI: -0.0113 to -0.0005, p = 0.03). Findings suggest that facial morphology may serve as a marker of impaired neuroectodermal development. Leveraging its association with attention problems enabled a robust examination of prenatal exposures' impact. The associations of maternal smoking, vitamin D, and folic acid concentrations with facial morphology provide insights into the origins of neurodevelopment.

Maternal deficiency of vitamin B12 (B12) is associated with neural tube defects, fetal growth restriction, and future risk of non-communicable disease in the offspring. Little is known about the molecular basis of these associations. We hypothesized that B12 regulates the expression of fetal genes, thereby influencing fetal growth and fetal programming. We investigated the association of B12 and other micronutrient concentrations in the cord blood with gene expression in the cord blood mononuclear cells. We performed a Weighted Gene Co-expression Network Analysis (WGCNA) on cord blood transcriptome of babies born in a pre-conception trial Pune Rural Intervention in Young Adolescents of B12 and multi-micronutrients (MMN). The gene modules (clusters) in WGCNA that showed a significant correlation with cord blood B12 and MMN were subjected to gene ontology (GO) analysis. WGCNA generated 23 different modules. Cord blood B12 concentrations were strongly correlated with modules of genes involved in methylation reactions and gene regulation. Cord B2 concentrations correlated with gene modules associated with demethylation reactions. Vitamins B6 and B9 did not show a unique association either with gene modules or specific GO terms. Our results demonstrate that maternal B12 may regulate expression of fetal genes involved in methylation reaction. This is a novel suggestion for the role of B12 in fetal growth, development, and the Developmental Origins of Health and Disease paradigm.

Research into the Developmental Origins of Health and Disease (DOHaD) has established links between environmental exposures in early life and later-life health outcomes. Emerging interventions typically focus on improving maternal nutrition and neonatal healthcare practices yet often neglect to assess or enhance subject understanding of potential long-term impacts or to communicate the benefits of maximising parental health prior to conception. This study critically evaluates a survey tool developed to measure knowledge of non-communicable diseases (NCDs) and early-life contributors to lifelong health. The rationale behind the wording and format of the questions is examined alongside options for coding and statistical interpretation of the data. Considerations for implementation are discussed, illustrated by key findings arising from tracking of the tool's application in Aotearoa New Zealand over ten years. We demonstrate that the survey tool can be adapted for use in a variety of contexts, producing both quantitative and qualitative baseline data suitable for informing health promotion interventions and monitoring changes in population knowledge. This research also highlights a key difference between awareness of and understanding of scientific concepts and the importance of distinguishing between these when considering public engagement with science.

In a normal pregnancy, glucocorticoids (GC), such as cortisol, play an essential role in early heart development. GC concentrations surge in late gestation to facilitate the maturation of fetal systems in preparation for birth. However, pregnancy complications related to stress, lifestyle factors, disease, and commonly used antenatal care treatments (GC therapy and artificial reproductive technology) can lead to prematurely increased GC concentrations that are detrimental to the heart before it is mature enough to benefit. These findings underpin the hypothesis that GC play a double-edged role that benefits normal heart development but is potentially harmful when dysregulated. However, the mechanisms by which both physiological and pathological elevations in GC concentrations influence the fetal cardiometabolic pathways that lead to detrimental long-term cardiovascular outcomes remain unclear. This review will, firstly, describe how cortisol regulates different aspects of cardiac development and, secondly, compare findings from different animal models that have provided mechanistic insight into how excess cortisol/GC during pregnancy impacts cardiac health across the life course.

The fetus and neonate are especially vulnerable to toxic effects of polychlorinated biphenyls (PCBs), that have been shown to perturb behavioral and neuropsychological development. This study aimed to examine the long-term effects of developmental exposure to PCBs. Doses selected were environmentally relevant to those found in epidemiological studies, on the central nervous system (CNS) of adult rat offspring. Pregnant Sprague Dawley rats were fed cookies that contained a mixture of fourteen PCBs or vehicle (corn oil) daily. PCB doses were 0.011 mg/kg maternal body weight/day ("low") or 1.10 mg/kg maternal body weight/day ("high"), for 42 days throughout gestation and lactation. Adult offspring were euthanized on postnatal day 450. A battery of immunohistochemical markers of brain structure and function were selected to assess possible effects of developmental PCB exposure. Using a 3×2 factorial design (treatment and sex), two-way analysis of variance revealed significant effects of treatment through the CNS, with no main effect of sex or interaction effects. In comparison with controls, both low and high dose developmental PCB exposure significantly (p < 0.05) increased inhibitory enzyme glutamic acid decarboxylase (GAD67) immunoreactivity in the cerebellar vermis, and decreased lipofuscin autofluorescence in the locus coeruleus (LC). Low dose developmental PCB exposure significantly decreased the perimeter of endothelial cells in the periaqueductal gray, ventral orbitofrontal cortex; and decreased lipofuscin in the dorsal striatum, compared to controls. Findings support the Developmental Origins of Health and Disease concept, which broadly posits that early-life perturbations may influence health trajectories over the lifespan.

Several studies have been published studying association between parental low birth weight (BW) and neonatal outcomes of their children. To date no systematic review and meta-analysis (SRM) has been published to quantify the impact of maternal and paternal BW on outcomes in the next generation. The aim of this SRM was to analyse the association between parental BW and anthropometric and metabolic outcomes in their children.Electronic databases were searched for studies documenting BW of parents and children with neonatal outcomes. Primary outcome was to evaluate impact of parental BW on occurrence of LBW in children. Secondary outcomes were to assess impact of parental BW on occurrence of macrosomia, small for gestational age (SGA), preterm labour/delivery, and burden of non-communicable disease in later life.We screened 54,961 articles, data from 14 studies (320,515 parent-child pairs), which fulfilled all criteria, were analysed. Maternal LBW was associated with higher chances of neonatal LBW [odds ratio (OR)1.95 (95% CI:1.56-2.46); P < 0.01; I² = 91%], neonatal SGA [OR 2.29(95% CI:1.72-3.05); P < 0.01; I² = 37%], lower chances of neonatal macrosomia [OR 0.50 (95% CI:0.39-0.65); P < 0.01; I² = 35%] and had no impact on preterm labour/delivery [OR1.20(95% CI:0.67-2.16); P = 0.53; I² = 88%]. Maternal macrosomia was associated with higher neonatal macrosomia [OR 2.66 (95% CI:2.44-3.16); P < 0.01; I² = 48%], lower SGA [OR 0.40(95% CI:0.29-0.53); P < 0.01; I² = 0%] and preterm labour/delivery [OR 0.77 (95% CI:0.63-0.94); P < 0.01; I² = 4%]. Paternal but not maternal LBW was predictor of metabolic syndrome and diabetes in adulthood.Maternal LBW is an important predictor of LBW and SGA in neonates. Maternal macrosomia is an important predictor of neonatal macrosomia; is protective against SGA and preterm labour/childbirth. Neonatal size of parents is reflected in neonatal size of their children.

Head circumference (HC) is a low-cost proxy for early brain development, yet few studies have examined its predictive value for specific neurocognitive outcomes in low- and middle-income countries. This study investigated whether trajectories of HC growth from 1 to 24 months predict executive function and fluid cognitive skills at age 4 in a Kenyan cohort (N = 182). Using latent growth curve modeling, we found that greater HC growth was significantly associated with better EF and fluid cognitive skills, independent of initial HC and sociodemographic factors. These associations were robust across subgroups defined by prenatal exposure to HIV and atypical physical growth (i.e., extreme values for weight-for-length, underweight, or HC). Moreover, the predictive association between early HC and later neurocognition was evident within the first 15 months of life. This study highlights the value of monitoring changes in HC as one aspect of early child health and wellbeing. Infants who do not exhibit normative increases in HC in infancy may benefit from early neurocognitive assessments and/or the receipt of early intervention services.

The COVID-19 pandemic intensified food insecurity (FI) and stress for many pregnant individuals, which may have contributed to adverse fetal developmental programming. This study aimed to identify key social determinants of health associated with pandemic-related FI and stress, and their association with gestational weight gain (GWG) and newborn birth weight in a Canadian pregnant cohort. Data were collected retrospectively from 273 pregnant individuals who delivered infants in Canada during the pandemic (March 2020-March 2023). Validated questionnaires were used to assess FI and pandemic-related stress, and GWG and infant birth weight were self-reported. FI was experienced by 55.7% of the participants, while 33.7% and 19.7% reported heightened stress related to COVID-19 infection and pregnancy preparedness, respectively. Participants from food-secure and food-insecure households differed significantly in parental structure, age, sexual orientation, housing status, household income, number of children in the household and pregnancy planning (all p values < 0.01). Heightened stress for both pregnancy preparedness and COVID-19 infection was also significantly associated with these same factors (all p values < 0.05) but not for age and housing status. FI and heightened stress were not associated with GWG outside the recommended range. However, significantly higher likelihood of birth weight extremes was observed with heightened COVID-19 infection-related stress (OR, 95% CI 1.50, 1.05-2.12, p = 0.02) and pregnancy preparedness-related stress (1.60, 1.10-2.31, p = 0.01), but not with FI. These findings underscore the influence of psychosocial factors on FI and stress during pregnancy, which may negatively impact infant health outcomes during the pandemic.

Small-for-gestational age (SGA) is an important global public health issue because of its increasing prevalence and long-term effects. Maternal smoking is a known risk factor for SGA; however, the effect of grandmaternal smoking on the risk of SGA in grandchildren SGA remains unclear. In this study, we examined whether grandmaternal smoking during pregnancy was associated with small birth weight, length, and head circumference for gestational age. Data were obtained from 23,730 pregnant women and their offspring from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Studies. A total of 1,130 grandmaternal-maternal-child triads were identified. Grandmaternal smoking during pregnancy was defined by the Maternal and Child Health Handbook owned by the mothers at birth mothers when they were born. Birth outcomes of grandchildren were obtained from medical records and converted to SGA using the 10^th percentile for weight, length, and head circumference. A multivariate logistic regression and propensity scores were used for the analysis. Prevalence of <10th percentile for birth weight, length, and head circumference in grandmaternal smokers were 10.2%, 2.0%, and 10.2%, respectively. Grandmaternal smoking during pregnancy was associated with the lower grandchild's birth weight (odds ratio (OR) [95% (CI)]: 2.86 [1.05-7.82]) and remained consistent when adjusted by propensity score (OR [95% CI]: 2.87 [1.04-7.92]). Grandmaternal smoking should not be ignored when assessing the SGA risk. Future work should consider the complex mediating relationship between smoking and growth restriction across generations.

Maternal diabetes during pregnancy, including pre-gestational and gestational diabetes mellitus (DM), can significantly affect fetal development, particularly in the kidneys. This study aimed to investigate the effects of maternal diabetes on fetal kidney size, parenchymal thickness, and renal artery hemodynamics using ultrasonography. A total of 128 pregnant women were enrolled and classified into pre-gestational DM (n = 28), gestational DM (n = 36), and control (n = 64) groups. Fetal kidney measurements, including anteroposterior, mediolateral, and longitudinal diameters as well as renal parenchymal thickness (RPT) and renal artery pulsatility index (PI), were assessed between 28 and 38 weeks of gestation. Fetal kidney volumes and their ratios to estimated fetal weight (EFW) and abdominal circumference (AC) were significantly lower in both the pre-gestational and gestational DM groups than in the controls (p < 0.05). However, no significant differences were observed in the RPT/AC ratios or renal artery PI among the groups. Furthermore, no significant correlations were found between maternal hemoglobin A1c (HbA1c) levels and fetal kidney or blood flow parameters. These findings suggest that maternal diabetes alters fetal kidney growth patterns relative to the overall fetal size, potentially reflecting developmental programming that may affect nephron endowment and long-term renal health. The lack of significant differences in RPT/AC ratios and renal artery PI may be attributed to effective diabetes management or limitations in detecting subtle changes using the current ultrasound methodologies. Further longitudinal studies with larger cohorts and postnatal follow-up are warranted to clarify long-term renal outcomes and explore the precise mechanisms underlying these developmental changes.