Journal of Developmental Origins of Health and Disease最新文献

Topiramate (TOP) is a psychotropic drug prescribed for the treatment of epilepsy in children older than 2 years of age and for migraine prophylaxis in adolescents. There is evidence that TOP promotes negative effects on the reproductive system of male rats. This study aimed to evaluate the immediate and late treatment effects of TOP during childhood and adolescence on the male rat reproductive system. Two experimental groups received 41 mg/kg of TOP daily, by gavage, from postnatal day (PND) 16 to 28 (TOPc group) or from PND 28 to 50 (TOPa group). Control groups (CTRc group or CTRa group) received water daily. Half of the anim-als were evaluated 24 h after the end of treatment (PND 29 and PND 51, respectively) and the remainder were evaluated in adulthood (PND120). The following parameters were determined: anogenital distance, sperm evaluation, testis' histomorphometry and plasma testosterone concentration. At PND 120, the volume (CTRc:62.58 ± 2.13; TOPc: 54.54 ± 2.10*%, p = 0.018) and total length (CTRc: 25.48 ± 1.61; TOPc: 18.94 ± 2.41*, p = 0.035) of seminiferous tubules were decreased and the volume of interstitial tissue (CTRc:37.41 ± 2.13; TOPc: 45.45 ± 2.09*%, p = 0.018) and number of Leydig cells/testis (CTRc: 277.00 ± 36.70; TOPc: 400.20 ± 13.23*, p = 0.013) were increased in the TOPc group. The other parameters remained similar between the groups. Therefore, the present study contributes to our understanding that childhood treatment with TOP has an impact on the rat reproductive system in adulthood, suggesting that this period is more sensitive to TOP exposure than adolescence.

Evidence clearly indicates that the nutritional and non-nutritional environment and level of physical activity during the early-life period from preconception through infancy has a lifelong impact on the child's health. However this message must be communicated effectively to parents and other stakeholders such as grandparents, health professionals, policymakers and the wider community in order for positive change to occur. This systematic review explores how both awareness and understanding of the long-term effects of the early-life environment have been measured in various populations and whether any patterns are evident. Ten articles were retrieved via a search of Embase, Medline and Scopus databases for peer-reviewed studies designed to assess participants' knowledge of the links between early-life exposures and adult health. Eligible articles spanned a wide range of countries, population groups and research methods. Three common themes were identified using thematic analysis: 1. a tendency for researchers to conflate participant understanding of the issue (the WHY) with a knowledge of key phrases and nutrition guidelines (the WHAT); 2. bias in both researchers and participants towards short-term thinking due to difficulty conceptualising long-term risk; and 3. challenges in comprehending the complexity of the evidence resulting in oversimplification and the overemphasis of maternal factors. Taken together these findings underscore the importance of a multi-level, whole-of-society approach to communicating the evidence, with the goal of influencing policy decisions as well as building a foundation of community support for parents and prospective parents to create a healthy early-life environment for the long-term wellbeing of all.

Exposure to a diet with a high saturated fat content can influence the characteristics of the gastrointestinal tract, causing losses in the absorption of nutrients and favoring the appearance of diseases. The objective was to assess the effects of a high-fat diet (HFD) in the perinatal (pregnancy and lactation) and post-weaning period on the histomorphometry, neuroplasticity, and histopathology of the ileum. Wistar rats were divided into four subgroups: Control/Control (CC, n = 10) rats fed a control diet (C) throughout the trial period; Control/HFD (CH, n = 9) rats fed diet C (perinatal) and HFD after weaning; HFD/Control (HC, n = 10) rats fed HFD (perinatal) and diet C (post-weaning); HFD/HFD (HH, n = 9) rats fed HFD throughout the experimental period. There was atrophy of the Ileum wall with a reduction in the muscular tunic, submucosa, and mucosa thickness in the HH group of 37%, 28%, and 46%, respectively (p < 0.0001). The depth of the crypts decreased by 29% (p < 0.0001) and height increased by 5% (p < 0.0013). Villus height decreased by 41% and 18% in HH and HC groups (p < 0.0001) and width decreased by 11% in the HH (p < 0.0001). The height of the enterocytes decreased by 18% in the HH (p < 0.0001). There was a decrease in the area of the myenteric and submucosal plexus ganglia in the HH and HC groups (p < 0.0001). The number, occupation, and granules of Paneth cells increased in the HH and HC groups (p < 0.0001). Intraepithelial lymphocytes (IELs) increased in all groups exposed to the HFD. Goblet cells decreased in groups CH and HH (p < 0.0001). The evidence from this study suggests that the HFD had altered the histomorphometry, neuroplasticity, and histopathology of the ileum of the rats.

One of the longstanding debates in life-course epidemiology is whether an adverse intrauterine environment, often proxied by birth weight, causally increases the future risk of cardiometabolic disease. The use of a discordant twin study design, which controls for the influence of shared genetic and environmental confounding factors, may be useful to investigate whether this relationship is causal. We conducted a discordant twin study of 120 monozygotic (MZ) and 148 dizygotic (DZ) twin pairs from the UK Biobank to explore the potential causal relationships between birth weight and a broad spectrum of later-life cardiometabolic risk factors. We used a linear mixed model to investigate the association between birth weight and later-life cardiometabolic risk factors for twins, allowing for both within-pair differences and between-pair differences in birth weight. Of primary interest is the within-pair association between differences in birth weight and cardiometabolic risk factors, which could reflect an intrauterine effect on later-life risk factors. We found no strong evidence of association in MZ twins between the within-pair differences in birth weight and most cardiometabolic risk factors in later life, except for nominal associations with C-reactive protein and insulin-like growth factor 1. However, these associations were not replicated in DZ twin pairs. Our study provided no strong evidence for intrauterine effects on later-life cardiometabolic risk factors, which is consistent with previous large-scale studies of singletons testing the potential causal relationship. It does not support the hypothesis that adverse intrauterine environments increase the risk of cardiometabolic disease in later life.

Prenatal exposure to dichlorodiphenyldichloroethylene (p,p´-DDE) may interfere with fetal development; however, studies evaluating anthropometry and gestational age at birth show inconsistent results. Typically, p,p´-DDE exposure has been measured during the third trimester and missed the key early pregnancy period. We evaluated the association between p,p´-DDE exposure before week 18 of pregnancy and anthropometry at birth, as well as gestational length, in 170 mother-child pairs from a cohort study in a flower-growing mexican region. Maternal serum p,p´-DDE concentrations were determined by gas chromatography. The associations between p,p´-DDE and z-scores of birth weight, birth length, and gestational age were evaluated by linear multiple regression models. Logistic regression models were used for low birth weight and small size for gestational age. Effect modification by child's sex was explored. The average gestational age at the blood sample extraction was 10.6 weeks. p,p'-DDE was detected in 64.7% of mothers, at a geometric mean of 0.24 ng/mL. Prenatal p,p´-DDE exposure was not associated with the birth outcomes in the whole sample. However, a high p,p´-DDE exposure was marginally associated with greater small for gestational age risk in male newborns (OR_{≥0.076ng/mL vs <0.076 ng/mL} = 3.09, 95% CI: 0.61; 15.58), but not in female (p for interaction = 0.08).Even though, we found no reductions in anthropometric measurements or gestational length associated with early prenatal p,p´-DDE exposure, the potential effect modification by infant's sex in terms of small for the gestational age risk deserves future studies.

Exposure to maternal hyperglycemia in utero has been associated with adverse metabolic outcomes in offspring. However, few studies have investigated the relationship between maternal hyperglycemia and offspring cortisol levels. We assessed associations of gestational diabetes mellitus (GDM) with cortisol biomarkers in two longitudinal prebirth cohorts: Project Viva included 928 mother-child pairs and Gen3G included 313 mother-child pairs. In Project Viva, GDM was diagnosed in N = 48 (5.2%) women using a two-step procedure (50 g glucose challenge test, if abnormal followed by 100 g oral glucose tolerance test [OGTT]), and in N = 29 (9.3%) women participating in Gen3G using one-step 75 g OGTT. In Project Viva, we measured cord blood glucocorticoids and child hair cortisol levels during mid-childhood (mean (SD) age: 7.8 (0.8) years) and early adolescence (mean (SD) age: 13.2 (0.9) years). In Gen3G, we measured hair cortisol at 5.4 (0.3) years. We used multivariable linear regression to examine associations of GDM with offspring cortisol, adjusting for child age and sex, maternal prepregnancy body mass index, education, and socioeconomic status. We additionally adjusted for child race/ethnicity in the cord blood analyses. In both Project Viva and Gen3G, we observed null associations of GDM and maternal glucose markers in pregnancy with cortisol biomarkers in cord blood at birth (β = 16.6 nmol/L, 95% CI -60.7, 94.0 in Project Viva) and in hair samples during childhood (β = -0.56 pg/mg, 95% CI -1.16, 0.04 in Project Viva; β = 0.09 pg/mg, 95% CI -0.38, 0.57 in Gen3G). Our findings do not support the hypothesis that maternal hyperglycemia is related to hypothalamic-pituitary-adrenal axis activity.

In this study, we empirically analyse whether in utero exposure to the Ramadan fasting period is negatively associated with child nutrition. The data for the analyses come from a retrospective assessment of 759,799 children from 103 Demographic and Health Surveys (DHS) across 56 countries during 2003-2020. Considering the month-long Ramadan exposure as a natural experiment, we implement an intent-to-treat framework, comparing stunting and underweight among children aged 0-5 years who were exposed to Ramadan fasting at any time in utero with those who were not exposed. Our findings do not show significant evidence to conclude that in utero exposure to the Ramadan fasting period is negatively associated with child nutrition. On the contrary, except for stunting in Muslim children who had in utero exposure to Ramadan fasting during the first months of pregnancy, we find no significant association between in utero exposure to Ramadan fasting and child stunting and underweight. Our main results are robust to multiple robustness checks.

Maternal prenatal psychological distress, which includes depression and anxiety, affects the onset of autism spectrum disorder (ASD). However, there is no consistent knowledge regarding at which term during pregnancy psychological distress affects the risk of ASD among children. We used a dataset obtained from the Japan Environment and Children's Study, which is a nationwide prospective birth cohort study, to evaluate the association between the six-item Kessler Psychological Distress Scale (K6) and ASD among 3-year-old children. A total of 78,745 children were analyzed, and 355 of them were diagnosed with ASD (0.45%). The maternal K6 was administered twice during pregnancy: at a median of 15.1 weeks (M-T1) and at that of 27.4 weeks (M-T2) of gestation. Multivariate logistic regression analyses demonstrated that the group with a maternal K6 score of ≥5 at both M-T1 and M-T2 was significantly associated with ASD among the children (adjusted odds ratio, 1.440; 95% confidence interval, 1.104-1.877) compared to the group with a score of ≤4 at both M-T1 and M-T2. There was no significant difference between the group with a score of ≥5 only at M-T1 or M-T2 and that with a score of ≤4 at both M-T1 and M-T2. In conclusion, from the first to the second half of pregnancy, continuous maternal psychological distress was associated with ASD among 3-year-old children. Contrarily, in the group without persistent maternal psychological distress during pregnancy, there was no significant association.

Exposure to pregnancy complications, including preeclampsia (PE), has lifelong influences on offspring's health. We have previously reported that experimental PE, induced in mice by administration of adenoviral sFlt1 at gestational day 8.5 combined with LPS at day 10.5, results in symmetrical growth restriction in female and asymmetrical growth restriction in male offspring. Here, we characterize the molecular phenotype of the fetal brain and liver with respect to gene transcription and DNA methylation at the end of gestation.In fetal brain and liver, expression and DNA methylation of several key regulatory genes is altered by PE exposure, mostly independent of fetal sex. These alterations point toward a decreased gluconeogenesis in the liver and stimulated neurogenesis in the brain, potentially affecting long-term brain and liver function. The observed sex-specific growth restriction pattern is not reflected in the molecular data, showing that PE, rather than tissue growth, drives the molecular phenotype of PE-exposed offspring.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler's Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother-child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; -2.01 [-3.43, -0.59], p = 0.006), verbal composite (-1.93 [-3.33, -0.53], p = 0.007), and information scale (-0.41 [-0.70, -0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%-41% and 7%-22%, respectively, and accounted for approximately 5%-10% greater variation in male children's cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.