Prenatal Exposure to Per- and Polyfluoroalkyl Substances and ASD-Related Symptoms in Early Childhood: Mediation Role of Steroids.

Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.

The midlife health of only children: chronic disease indicators and biomarkers by sibship size in three nationally representative UK cohorts.

BACKGROUND: Despite persistent concerns about only children's disadvantage relative to individuals with siblings, existing health-related evidence is inconsistent. Recent evidence from Nordic countries about only children having poorer health outcomes may not apply elsewhere because selection processes differ across contexts. We investigate the midlife health of only children in the UK where one-child families tend to be socio-economically advantaged relative to large families. METHODS: Using the 1946, 1958 and 1970 British birth cohort studies, we examine various biomarkers and self-reported measures of chronic disease by sibship size when respondents are aged in their mid-40s, mid-50s and mid-60s. We estimate separate linear probability models for each cohort, age and outcome, adjusting for childhood and early adulthood circumstances. RESULTS: We found no evidence of only children differing from those with one, two or three or more siblings, at any age, in any of the cohorts, on: heart problems, hypertension, high triglycerides, high glycated haemoglobin or high C-reactive protein. However, compared with only children, the probability for cancer (0.019, 95% confidence interval [CI]: 0.002, 0.035; age 46/1970) and poor general health (0.060, CI: 0.015, 0.127; age 55/1958; and 0.110, CI: 0.052, 0.168; age 63/1946) was higher among those with three or more siblings. CONCLUSIONS: There is no consistent pattern of only child health disadvantage for midlife chronic disease outcomes across ages or cohorts in the UK. Research should focus on better understanding how sibship size differentials are contingent on context.

Could environmental exposure and climate change Be a key factor in the rising incidence of early onset colorectal cancer?

The emergence of early onset colorectal cancer (EOCRC) is believed to result from the complex interplay between external environmental factors and internal molecular processes. This review investigates the potential association between environmental exposure to chemicals and climate change and the increased incidence of EOCRC, focusing on their effects on gut microbiota (GM) dynamics. The manuscript explores the birth cohort effect, suggesting that individuals born after 1950 may be at higher risk of developing EOCRC due to cumulative environmental exposures. Furthermore, we also reviewed the impact of environmental pollution, including particulate matter and endocrine disrupting chemicals (EDCs), as well as global warming, on GM disturbance. Environmental exposures have the potential to disrupt GM composition and diversity, leading to dysbiosis, chronic inflammation, and oxidative stress, which are known risk factors associated with EOCRC. Particulate matter can enter the gastrointestinal tract, modifying GM composition and promoting the proliferation of pathogenic bacteria while diminishing beneficial bacteria. Similarly, EDCs, can induce GM alterations and inflammation, further increasing the risk of EOCRC. Additionally, global warming can influence GM through shifts in gut environmental conditions, affecting the host's immune response and potentially increasing EOCRC risk. To summarize, environmental exposure to chemicals and climate change since 1950 has been implicated as contributing factors to the rising incidence of EOCRC. Disruptions in gut microbiota homeostasis play a crucial role in mediating these associations. Consequently, there is a pressing need for enhanced environmental policies aimed at minimizing exposure to pollutants, safeguarding public health, and mitigating the burden of EOCRC.

Aging-related changes in protein and fat intake and their related meal types factors by longitudinal birth cohort analysis using the National Health and Nutrition Survey in Japan from 2001 to 2019.

BACKGROUND: To provide seamless nutritional support from early adulthood to late adulthood in Japan, this study aimed to identify aging-related changes in protein and fat intake and meal types. METHODS: Birth cohort analysis was conducted in this study. The protein intake, protein-to-energy ratio, fat intake, and fat-to-energy ratio in men and women from their 20s to 60s in 2001 was calculated using the data of the National Health and Nutrition Survey in Japan between 2001 and 2019 (n = 139,876, 47.0% men, mean age: 54.9 and 55.4 years for men and women, respectively). The intakes were calculated for every subsequent year, the aging-related changes were identified by age group, and the 99 food groups were classified into staple-focused meal types through factor analysis. The weighted average component value per 1 g of each food group was calculated, multiplied by the food weight, and totaled to determine the mean intake by meal type and to confirm the aging-related changes. The year when the slope changed before and after was identified through Joinpoint regression analysis. RESULTS: The protein intake, protein-to-energy ratio, fat intake, and fat-to-energy ratio initially declined or remained unchanged with aging in almost all generations (20s to 60s in 2001) but began to increase after 8-15 years. The food groups were classified into rice, noodle, and bread types. The protein and fat intake from the noodle type initially showed a decreasing trend but began to increase with aging after 8-15 years in almost all generations in both sexes (p < 0.05 for difference in slope). CONCLUSIONS: The increase of protein intake and protein-to-energy ratio and fat intake and fat-to-energy ratio over time observed among Japanese adults may be related to the increased intake of food groups from noodle type meals. Thus, considering the type of staple food (i.e., rice, noodles, or bread) and its combination with other foods when adhering to a balanced diet is necessary.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood bone mineral density: A prospective birth cohort study.

BACKGROUND AND AIM: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have demonstrated potential toxicity in skeletal development. However, the relationship between prenatal PFAS exposure and offspring bone health remains unclear in epidemiological studies. Therefore, we aim to investigate whether prenatal exposure to PFAS is associated with bone mineral density (BMD) in offspring. METHOD: This study population included 182 mother-child pairs in the Shanghai Obesity and Allergy Cohort, enrolled during 2012-2013. 10 PFAS were measured by liquid chromatography-mass spectrometry (LC-MS) in cord plasma. The child's spinal BMD was measured using a dual-energy X-ray absorptiometry (DXA) scanner at the age of 8. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into quartiles) and child BMD. Bayesian kernel machine regression (BKMR) was employed to explore the joint effects of PFAS mixtures on BMD. RESULTS: Among the 10 PFAS, 8 of them had a detection rate >90% and were included in the subsequent analysis. We observed no significant associations between individual PFAS (as a continuous variable) and spinal BMD in 8-year-old children using the multivariable linear regression model. When treated as quartile categories, the second and fourth quartiles of perfluorobutane sulfonate (PFBS) was associated with higher BMD in the first lumbar vertebra, compared with the lowest quartile. BKMR analysis revealed no association between the PFAS mixture and child BMD. CONCLUSION: We observed no associations of prenatal PFAS exposure with child BMD at 8 years of age. Given the inconsistent epidemiological evidence, further research is needed to confirm these findings from other studies or elucidate the potentially toxic effects of PFAS on bone.

Associating prenatal antibiotics exposure with attention deficit hyperactivity disorder symptoms in preschool children: The role of maternal vitamin D.

BACKGROUND: The associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored. OBJECTIVES: To evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers' ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D. METHODS: Based on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual-oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status. RESULTS: Compared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester. CONCLUSIONS: Maternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms.

Defining familial longevity and developing a familial longevity score for unbiased epigenetic studies in a birth cohort.

Aim: Longevity accumulating in families has genetic and epigenetic components. To study early and unbiased epigenetic predictors of longevity prospectively, a birth cohort would be ideal. However, the original family longevity selection score (FLoSS) focuses on populations of elderly only.Methods: In the German birth cohort KUNO-Kids we assessed when information for such scores may be best collected and how to calculate an adapted FLoSS.Results: A total of 551 families contributed to adapted FLoSS, with a mean score of -0.15 (SD 2.33). Adapted FLoSS ≥7 as a marker of exceptional longevity occurred in 3.3% of families, comparable to original FLoSS in elderly.Conclusion: An adapted FLoSS from data collectable postnatally may be a feasible tool to study unbiased epigenetic predictors for longevity.

In the German birth cohort KUNO-Kids we assessed if and how a family longevity selection score may best be calculated to study unbiased epigenetic predictors for longevity in the future.

Association between mode of delivery and early neurodevelopment: A prospective birth cohort study.

Previous research has assessed the effects of caesarean delivery (CD) on child neurodevelopment; however, whether the effects stem from the surgical procedure itself or its related medical conditions has not been conclusively determined. This study aimed to evaluate the associations among delivery mode, CD-related medical conditions and early childhood neurodevelopment. A total of 3829 maternal-infant pairs from a longitudinal birth cohort in Wuhan City, China, were included in the primary analysis. The neurodevelopment of the children was assessed by the Bayley Scales of Infant Development (BSID), the Conners Comprehensive Behaviour Rating Scale and the Chinese version of the Autism Behavior Checklist. Data on delivery mode and medical conditions were collected via medical records from the study hospital. Among the 3829 children for whom the BSID test was completed at two years of age, 50%, 27%, and 23% were delivered vaginally, by necessary CD, and by elective CD, respectively. Compared with vaginally delivered children, Necessary CD was associated with a 16.67% decrease in Mental Development Index (MDI) scores and a 13.37% decrease in Psychomotor Development Index (PDI) scores, while elective CD showed a 20.63% and 20.99% decrease after FDR correction, respectively. Similarly, among the 2448 children for whom the CBRS was completed, necessary CD was found to be associated with conduct disorders (adjusted ß: 0.06; 95% CI: 0.02, 0.09), hyperactivity (adjusted ß: 0.06; 95% CI: 0.02, 0.11), and hyperactivity index (adjusted ß: 0.07; 95% CI: 0.03, 0.11), while elective CD was significantly associated with hyperactivity problem scores (adjusted ß: 0.08, 95% CI: 0.03, 0.13). However, no significant association was found between CD and symptoms of autism in children, as assessed by the Autism Behavior Checklist (ABC). CONCLUSION: This study suggested that the adverse impact of CD on child neurodevelopment stems from the procedure itself rather than CD-related medical conditions. It is important to minimize the use of CD when there is no medical necessity. WHAT IS KNOWN: • Caesarean delivery (CD) may influence child neurodevelopment and other long-term outcomes. • In China, approximately one-quarter of CD are performed due to maternal request without medical indications. WHAT IS NEW: • The negative impact of CD on the neurodevelopmental outcomes of children may be primarily attributed to the procedure itself, as opposed to related medical conditions. • In the absence of medical indications, unnecessary CD may have adverse impacts on children's neurodevelopment.

Association Between Periconceptional Diet Quality and Hypertensive Disorders of Pregnancy: The Japan Environment and Children's Study.

BACKGROUND: Little is known about the relationship of healthy diets, which are widely recommended to prevent diseases in general populations, with the risk of hypertensive disorders of pregnancy (HDP), particular among non-Western populations with different dietary habits. We aimed to investigate the association between periconceptional diet quality and the risk of HDP among pregnant Japanese women. METHODS AND RESULTS: Dietary intake over 1 year before the first trimester of pregnancy was assessed using a validated, self-administered food frequency questionnaire among 81 113 pregnant Japanese women who participated in a prospective cohort of the Japan Environment and Children's Study. Overall diet quality was assessed by the Balanced Diet Score (BDS) based on adherence to the country-specific dietary guidelines and the Dietary Approaches to Stop Hypertension (DASH) score. Cases of HDP were identified by medical record transcription. The association between diet quality and HDP risk was examined using Bayesian logistic regression models with monotonic effects. We identified 2383 (2.9%) cases of HDP. A higher BDS was associated with a lower risk of HDP. When comparing the highest with the lowest quintile of the BDS, the adjusted odds ratio (aOR) of HDP was 0.83 (95% credible interval [CrI], 0.73-0.94). The DASH score and HDP risk were inversely associated in a monotonic dose-response manner (aOR per 1-quintile increase in the DASH score, 0.92 [95% CrI, 0.89-0.95]). CONCLUSIONS: A high-quality diet, which is recommended for disease prevention in general populations, before conception may also reduce the risk of HDP among pregnant Japanese women.

Epidemiology of Pediatric Astrovirus Gastroenteritis in a Nicaraguan Birth Cohort.

Background: Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low- and middle-income countries. Methods: We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections, and time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. Results: Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. Conclusions: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.

Long-term effects on growth in preterm and small for gestational age infants: A national birth cohort study.

BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.

Association between high birth weight and dental caries at 4-5 years of age: a birth-cohort study.

OBJECTIVE: Early childhood caries has become a globally crucial oral health problem over the decades. Most studies have discussed the association between low birth weight and early childhood caries; however, studies focusing on high birth weight have been relatively limited. This study aimed to assess the impact of high birth weight on the incidence and severity of dental caries in 4-5-year-old children. SUBJECTS AND METHODS: Study subjects included 491 children from a birth cohort study at 4-5 years of age. Data on dental caries, prenatal and perinatal factors, and socio-demographic determinants were recorded. Logistic regression models adjusted for potential confounders were performed to analyze the data. Two-sided P-value < 0.05 was considered statistically significant. RESULTS: Of the 491 children, the prevalence of dental caries was 48.7%. High birth weight (≥ 4,000 g) was significantly associated with increased incidence of dental caries (OR, 2.000; CI 95% 1.062-3.765), and the relatively enhanced risk OR was further increased in subjects experiencing caries (dmft ≥ 3) (OR, 2.437; CI 95% 1.306-4.549) compared with the normal birth weight (2,500-3,999 g). CONCLUSIONS: High birth weight is a risk factor for early childhood caries. Particular attention should be paid to children with birth weight more than or equal to 4,000 g.

Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry.

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504). Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts. Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers. Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.

Febrile seizures and childhood epilepsy and risk of internalizing and psychotic symptoms.

OBJECTIVE: To assess whether children with febrile seizures and/or epilepsy were at increased risk of experiencing internalizing symptoms or psychotic-like experiences at age 11 years. METHODS: This cohort study includes 44 819 children from the 11-year follow up of the Danish National Birth Cohort. Information on childhood seizures was retrieved from the Danish National Patient Registry, whereas child psychiatric symptoms were assessed in a web-based questionnaire using the Adolescent Psychotic-like Symptom Screener and the Strength and Difficulties Questionnaire. Adjusted odds ratios (aORs) with corresponding 95% confidence intervals (CIs) for the association between childhood seizures and internalizing symptoms (symptom score ≥8) and psychotic-like experiences (≥2 definite experiences) were obtained using logistic regression models. RESULTS: A total of 1620 children with febrile seizures (3.6%), and 311 children with epilepsy (0.7%) were identified. When adjusted for potential confounders, no association between febrile seizures and psychiatric symptoms was observed, and no association was observed between epilepsy and psychotic-like experiences. However, the OR for internalizing symptoms was 1.76 (95% CI: 1.20-2.58) in children with epilepsy compared to children without. This higher risk was evident mainly in boys (OR 2.30, 95% CI 1.37-3.85), children with ≥2 epilepsy-related hospital admissions (OR 2.79, 95% CI 1.81-4.32), and children whose age at first epilepsy-related hospital admission was 0-3 years (OR 2.47, 95% CI 1.45-4.19). SIGNIFICANCE: No association was found between febrile seizures and psychiatric symptoms or epilepsy and psychotic-like experiences at age 11. However, boys with epilepsy were at higher risk of experiencing internalizing symptoms.

Do people reach 100 by surviving, delaying, or avoiding diseases? A life course comparison of centenarians and non-centenarians from the same birth cohorts.

Centenarians are perceived as pioneers of longevity, possessing the secrets to surpassing age 100. It remains unclear whether they achieve this by surviving, delaying, or avoiding diseases to a greater extent than their shorter-lived peers. This register-based study encompassed all individuals aged 60 and older, born between 1912 and 1922 in Stockholm County, Sweden (N = 170,787). Using historical data, individuals were prospectively followed from 1972 to 2022 and stratified by their age at death. Age-specific incidence rates and remaining lifetime risk from age 60 were calculated for stroke, myocardial infarction, hip fracture, and various cancers (including colorectal, breast, and prostate), and compared between those who survived to age 100 and their shorter-lived counterparts. Centenarians had lower age-specific incidence rates for almost all diseases and ages. Despite longer life spans, their lifetime risks for all diseases except hip fracture were lower than those of non-centenarians. This suggests that centenarians delay, and even avoid, many of the major age-related diseases rather than surviving them to a higher extent. The findings that centenarians not only exhibit lower disease rates at younger ages compared to their shorter-lived peers but throughout their lives challenge the notion that longer life span inevitably leads to higher disease rates or a simple shift of diseases to older ages.

Association between physical activity and cardiovascular parameters in 7-year-old children: a Chinese cross-sectional study.

INTRODUCTION: Physical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children. METHODS: Follow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children's PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children. RESULTS: Overall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, ß coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, ß = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (ß = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (ß = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, ß = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (ß = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (ß = -0.42, 95% CI: -0.78, -0.06). CONCLUSIONS: This study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.

Impact of wheat sensitization on wheeze and T2 phenotypes in general population of children.

Background: The association between sensitization to specific aeroallergens and outcomes in patients with asthma is well researched; however, the association between childhood-onset wheeze/asthma and sensitization to various aeroallergens and food allergens in the general pediatric population remains poorly understood. Objective: We sought to investigate the association between sensitization to common aeroallergens and food allergens with wheeze and type 2 (T2) inflammation in the general pediatric population. Methods: Specific IgEs against 9 aeroallergens and 4 food allergens were measured in the prospective Hokkaido birth cohort of 428 school-age children (age ∼10 years). Wheeze and other allergic symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. Blood eosinophil count and fractional exhaled nitric oxide level were assessed as T2 biomarkers. The Isle of Wight birth cohort in the United Kingdom was used for replication analysis (n = 1032). Results: The prevalence of sensitization to at least 1 aeroallergen and food allergen was 70.5% and 22.3%, respectively. A significant association between wheeze and sensitization to aeroallergens such as ragweed, Japanese cedar, mugwort, and pet dander was found. However, the association between wheeze and wheat sensitization was highly significant (Hokkaido birth cohort: odds ratio, 4.67; 95% CI, 1.98-11.01; Isle of Wight birth cohort, odds ratio, 4.01; 95% CI, 1.78-9.07). Sensitization to most aeroallergens, though not any food allergen, was associated with the T2-high phenotype. Conclusions: Sensitization to wheat may be an important risk factor for wheeze/asthma development, especially the pathogenesis of T2-non/low asthma, independent of aeroallergens, in the general pediatric population.

Trajectories of egg sensitization in childhood: Two birth cohorts in Asia and Europe.

BACKGROUND: Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss-of-function mutations on the natural history of egg sensitization lacks consensus among studies. OBJECTIVE: To evaluate the association between the natural course of egg sensitization and FLG mutations. METHODS: We used Japanese and the UK birth cohorts (CHIBA and MAAS) to identify the longitudinal patterns of egg sensitization until mid-school age and examined the relationship between the identified patterns and FLG mutations. Sensitization was assessed using egg white-specific IgE levels or skin prick tests (SPTs). Egg allergy was confirmed by parental reports and sensitization. Latent class growth analysis identified longitudinal patterns. RESULTS: Three similar patterns of egg sensitization (persistent, early-onset remitting, and no/low grade classes) were identified in both cohorts, with differing prevalence estimates. The proportion of children with egg allergy in the persistent class at 7 or 8 years of age was 23% (CHIBA) and 20% (MAAS). Consistently in both cohorts, FLG mutations were significantly associated only with the persistent class. Children with FLG mutations had an approximately four-fold increased risk of being in the persistent sensitization class (RRRs: 4.3, 95%C.I. (1.2-16.0), p = .03 in CHIBA; 4.3 (1.3-14.7), p = .02 in MAAS). CONCLUSION: FLG loss-of-function mutations are associated with persistent egg sensitization in both Japanese and European ethnicities, and the mutations might be a potential biomarker for identifying the risk of persistent egg sensitization/allergy in early infancy. Future studies should incorporate oral food challenges to confirm this relationship.