Exploring the Link between Social Support and Patient-Reported Outcomes in Chronic Obstructive Pulmonary Disease Patients: A Cross-Sectional Study in Primary Care.

We aimed to explore the link between social support and various patient-reported outcome measures (PROMs) in primary care patients with COPD. This was a cross-sectional study with 168 patients with COPD from six primary care centers in Crete, Greece. We collected data on sociodemographic characteristics, medical history, disease-specific quality of life, the COPD Assessment Test (CAT), fatigue, the Fatigue Severity Scale (FSS), phycological parameters, Patient Health Questionnaire-9, General Anxiety Disorder-7, sleep complaints, the Pittsburg Sleep Quality Index, the Athens Insomnia scale (AIS), and the Epworth Sleepiness Scale. Social support was measured using the Multidimensional Scale of Perceived Social Support (MSPSS). Out of 168 patients with COPD, 114 (68.9%) exhibited low levels of social support. Low social support (MSPSS total ≤ 5) was positively associated with COPD symptoms (CAT score ≥ 10) (OR = 3.97, 95%CI:1.86-8.44; p < 0.01), fatigue (FSS ≥ 36) (OR = 2.74, 95%CI:1.31-5.74; p = 0.01), and insomnia symptoms (AIS ≥ 6) (OR = 5.17 95%CI:2.23-12.01; p < 0.01), while the association with depressive symptoms (PHQ-9 ≥ 10) was marginally significant (OR = 3.1, 95%CI:0.93-10.36; p = 0.07). Our results suggest that lower levels of social support are positively associated with PROMs in patients with COPD. Therefore, our findings show an additional way to improve the overall health of patients with COPD in primary care by putting social support at the epicenter of actions.

The Effectiveness of Teaching the Teacher Interventions in Improving the Physical Activity among Adolescents in Schools: A Scoping Review.

Physical inactivity is a leading risk factor for global mortality as it increases the risk of non-communicable diseases and decreases overall health. Therefore, increasing physical activity (PA) is strongly recommended, particularly in adolescents. The Teaching the Teachers (TTT) approach is a prominent example of an intervention that could enhance PA levels in adolescents. However, available evidence on the efficacy of TTT interventions in promoting PA among adolescents is either limited or inconclusive. Therefore, a scoping review was conducted to provide an overview of the current state of knowledge regarding the effectiveness of TTT interventions in improving the PA of adolescent students. The PRISMA-Scoping methodology was employed, and articles in the Medline database were searched. We screened 2357 articles for inclusion, and finally included 16 articles. Most articles were conducted in European countries. The TTT interventions appeared to positively affect various aspects of PA. These aspects include support for personal autonomy, intent to engage in PA, improvements in body composition and fitness level, social support, enjoyment of Physical Education (PE), and positive attitudes towards PE. Consequently, policymakers could utilize TTT interventions to improve the physical activity of adolescents, which may reduce the burden of non-communicable diseases and foster healthier societies.

Prenatal air pollution exposure and childhood obesity: Effect modification by maternal fruits and vegetables intake.

BACKGROUND & AIMS: Prenatal exposure to air pollution is robustly associated with fetal growth restriction but the extent to which it is associated with postnatal growth and the risk of childhood obesity remains unknown. We examined the association of prenatal exposure to air pollution with offspring obesity related measures and evaluated the possible protective effect of maternal fruits and vegetables intake (FV). METHODS: We included 633 mother-child pairs from the Rhea pregnancy cohort in Crete, Greece. Fine particles (PM2.5 and PM10) exposure levels during pregnancy were estimated using land-use regression models. We measured weight, height and waist circumference at 4 and 6 years of age, and body composition analysis was performed at 6 years using bioimpedance. Maternal diet was evaluated by means of a semi-quantitative food frequency questionnaire in mid-pregnancy. Adjusted associations were obtained via multivariable regression analyses and multiplicative interaction was used to evaluate the potential modifying role of FV intake. RESULTS: Exposure to PMs in utero was not associated with measures of adiposity at 4 or 6 years of age. Associations at 4 years did not differ according to maternal consumption of FV. However, at 6 years, among children whose mothers reported consuming less than 5 servings of FV per day, one SD increase in PM10 during pregnancy was associated with increased BMI (beta 0.41 kg/m2, 95% CI: -0.06, 0.88, p-interaction = 0.037) and increased waist circumference (beta 0.83 cm, 95% CI: -0.38, 2.05, p-interaction = 0.043) and one SD increase in PM2.5 was associated with increased fat mass (beta 0.5 kg, 95% CI: 0.0, 0.99, p-interaction = 0.039) and increased percentage of body fat (beta 1.06%, 95% CI: -0.06, 2.17, p-interaction = 0.035). Similarly, higher prenatal PM2.5 and PM10 exposure was associated with increased risk for obesity and abdominal obesity at 6 years only in the low FV group. CONCLUSIONS: Exposure to fine particulate matter during pregnancy was not associated with obesity-related measures at 4 and 6 years. However, only among offspring of mothers who consumed inadequate FV, we observed higher obesity-related measures at 6 years. Our results indicate that mothers' diet during pregnancy may play a role in the relationship between air-pollution and childhood obesity.

Lifestyle patterns in European preschoolers: Associations with socio-demographic factors and body mass index.

BACKGROUND: Energy balance-related behaviours (EBRBs), that is, dietary intake, screen, outdoor play and sleep, tend to combine into 'lifestyle patterns', with potential synergistic influences on health. To date, studies addressing this theme mainly focused on school children and rarely accounted for sleep, with a cross-country perspective. OBJECTIVES: We aimed at comparing lifestyle patterns among preschool-aged children across Europe, their associations with socio-demographic factors and their links with body mass index (BMI). METHODS: Harmonized data on 2-5-year-olds participating in nine European birth cohorts from the EU Child Cohort Network were used (EBRBs, socio-demographics and anthropometrics). Principal component analysis and multivariable linear and logistic regressions were performed. RESULTS: The most consistent pattern identified across cohorts was defined by at least three of the following EBRBs: discretionary consumption, high screen time, low outdoor play time and low sleep duration. Consistently, children from low-income households and born to mothers with low education level had higher scores on this pattern compared to their socioeconomically advantaged counterparts. Furthermore, it was associated with higher BMI z-scores in the Spanish and Italian cohorts (ß = 0.06, 95% CI = [0.02; 0.10], both studies). CONCLUSION: These findings may be valuable in informing early multi-behavioural interventions aimed at reducing social inequalities in health at a European scale.

Influenza Vaccination Coverage Rates and Determinants in Greek Children until the Age of Ten (2008-2019), the Rhea Mother-Child Cohort.

BACKGROUND: In Greece, influenza vaccination is currently recommended for children with high-risk conditions. There are limited data on influenza vaccination uptake among Greek children with and without high-risk conditions. We aim to describe the annual influenza vaccination uptake until the age of ten in a population-based mother-child cohort and identify the factors influencing vaccination rates. METHODS: Immunization data from the child's health cards at 4 and 10 years were available for 830 and 298 children participating in the Rhea cohort (2008-2019). We calculated vaccination coverage by age, winter season and among children with asthma and obesity for whom the vaccine is indicated. Univariable and multivariable stepwise logistic regression models were utilized to identify the association between several sociodemographic, lifestyle and health-related variables and vaccine uptake by age four. RESULTS: By the ages of four and ten, 37% and 40% of the children, respectively, had received at least one influenza vaccination. Only 2% of the children were vaccinated for all winter seasons during their first four years of life. The vaccination rate was highest at the age of two and during the 2009-2010 season. Vaccination rates for children with asthma and obesity were 18.2% and 13.3% at age four and 8.3% and 2.9% at age ten. About 10% of all vaccines were administered after December and 24% of the children received only one dose upon initial vaccination. Children with younger siblings and those who had experienced more respiratory infections were more likely to be vaccinated by the age of four, while children exposed to smoking were less likely to be vaccinated. CONCLUSIONS: Children in our study were more likely to be vaccinated against influenza at an early age with the peak occurring at the age of two. Nonetheless, annual vaccination uptake was uncommon. Vaccination rates of children with asthma and obesity were well below the national target of 75% for individuals with chronic conditions. Certain groups may merit increased attention in future vaccination campaigns such as children raised in families with unfavourable health behaviours.

Maternal sleep disturbances during late pregnancy and child neuropsychological and behavioral development in early childhood.

The present study aims to explore the association of maternal sleep disturbances during late pregnancy on child neuropsychological and behavioral development in preschool years. The study included 638 mother-child pairs from the prospective Rhea mother-child cohort in Crete, Greece. Information on antenatal sleep disturbances was collected through a computer-assisted interview. Children's neuropsychological and behavioral development was assessed using the McCarthy Scales of Children's Abilities (MSCA), the Attention-Deficit Hyperactivity Disorder Test (ADHDT), and the Strengths and Difficulties Questionnaire (SDQ). Multivariate analysis showed that maternal sleep duration less than 8 h was associated with reduced scores in the general cognitive scale (ß = -2.28, 95% CI -4.54, -0.02, R2 = 0.417) and memory span (ß = -3.24, 95% CI -5.72, -0.77, R2 = 0.304), while mild-severe daytime sleepiness was associated with reduced scores in the memory scale (ß = -5.42, 95% CI -10.47, -0.37, R2 = 0.304), memory span (ß = -5.44, 95% CI -10.68, -0.21, R2 = 0.304), nd functions of posterior cortex (ß = -5.55, 95% CI -10.40, -0.70, R2 = 0.393) of MSCA. Snoring in late pregnancy was related to higher child hyperactivity scores in SDQ (ß = 1.05, 95% CI 0.16, 1.95, R2 = 0.160). An interaction between child sex and maternal sleep duration in response to ADHD symptoms was also found (p for interaction < 0.05). Stratified analysis revealed increased hyperactivity, inattention, and ADHD total scores for girls of mothers with sleep duration less than 8 h. Maternal sleep disturbances during pregnancy may be associated with impaired child neuropsychological and behavioral development during the preschool years. Early detection and intervention is necessary to reduce sleep disturbances habits in pregnancy and improve child neurodevelopment.

Prenatal exposure to multiple organochlorine compounds and childhood body mass index.

Background: Prenatal exposure to organochlorine compounds (OCs) has been associated with increased childhood body mass index (BMI); however, only a few studies have focused on longitudinal BMI trajectories, and none of them used multiple exposure mixture approaches. Aim: To determine the association between in-utero exposure to eight OCs and childhood BMI measures (BMI and BMI z-score) at 4 years and their yearly change across 4-12 years of age in 279 Rhea child-mother dyads. Methods: We applied three approaches: (1) linear mixed-effect regressions (LMR) to associate individual compounds with BMI measures; (2) Bayesian weighted quantile sum regressions (BWQSR) to provide an overall OC mixture association with BMI measures; and (3)Bayesian varying coefficient kernel machine regressions (BVCKMR) to model nonlinear and nonadditive associations. Results: In the LMR, yearly change of BMI measures was consistently associated with a quartile increase in hexachlorobenzene (HCB) (estimate [95% Confidence or Credible interval] BMI: 0.10 [0.06, 0.14]; BMI z-score: 0.02 [0.01, 0.04]). BWQSR results showed that a quartile increase in mixture concentrations was associated with yearly increase of BMI measures (BMI: 0.10 [0.01, 0.18]; BMI z-score: 0.03 [0.003, 0.06]). In the BVCKMR, a quartile increase in dichlorodiphenyldichloroethylene concentrations was associated with higher BMI measures at 4 years (BMI: 0.33 [0.24, 0.43]; BMI z-score: 0.19 [0.15, 0.24]); whereas a quartile increase in HCB and polychlorinated biphenyls (PCB)-118 levels was positively associated with BMI measures yearly change (BMI: HCB:0.10 [0.07, 0.13], PCB-118:0.08 [0.04, 012]; BMI z-score: HCB:0.03 [0.02, 0.05], PCB-118:0.02 [0.002,04]). BVCKMR suggested that PCBs had nonlinear relationships with BMI measures, and HCB interacted with other compounds. Conclusions: All analyses consistently demonstrated detrimental associations between prenatal OC exposures and childhood BMI measures.

Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health.

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1H NMR spectroscopy in a multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N-methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children's diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.

Sex specific associations between in utero exposure to persistent organic pollutants and allergy-related outcomes in childhood: The Rhea Mother-Child Cohort (Crete, Greece).

Accumulating evidence suggests that in utero exposures can influence the development of the immune system. Few studies have investigated whether prenatal exposure to persistent organic pollutants (POPs) is associated with allergy-related phenotypes in childhood, nor explored sex differences. We examined the association between prenatal exposure to POPs and offspring allergic outcomes in early and mid-childhood. We included 682 mother-child pairs from the prospective birth cohort Rhea. We measured dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and 6 polychlorinated biphenyl (PCB) congeners in maternal first trimester serum. Parents completed the questionnaires adapted from the International Study on Asthma and Allergy in Childhood (ISAAC) for allergy-related phenotypes when their children were 4 and 6 years old. We used Poisson regression models to estimate Risk Ratios. Prenatal HCB was associated with increased risk for rhinoconjunctivitis at 6 years (RR (95% CI): 2.5; (1.3, 4.8) for a doubling in the exposure). Among girls, prenatal DDE was associated with increased risk for current wheeze, current asthma and current rhinoconjunctivitis at 4 years (RR (95%CI): 1.4 (0.8, 2.6), 1.6 (1.1, 2.4) and 1.8 (1.0, 3.3) and p-interaction = 0.035, 0.027 and 0.059, respectively), with increased risk for current rhinoconjunctivitis at 6 years (RR (95%CI): 1.7 (0.7, 3.8) and p-interaction = 0.028) and total PCBs were associated with increased risk for current eczema at 4 years (RR (95%CI): 2.1 (1.1, 4.2) and p-interaction = 0.028). In boys, prenatal DDE was associated with decreased risk for current wheeze and current asthma at 4 years. Our findings suggest that even low levels of exposure to POPs prenatally may affect the development of childhood allergy-related outcomes in a sex and age-specific manner.

Prenatal and infant antibiotic exposure and childhood growth, obesity and cardiovascular risk factors: The Rhea mother-child cohort study, Crete, Greece.

BACKGROUND: Early-life antibiotic use has been hypothesized to promote weight gain and increase the risk of childhood obesity. OBJECTIVES: To examine the associations of prenatal and infant antibiotics with childhood growth, adiposity and cardiometabolic traits in the Greek Rhea cohort. METHODS: We used data from 747 mother-child pairs with anthropometric measurements drawn from medical records or measured at 4 and 6 years of age. Antibiotic exposure was assessed by maternal report during pregnancy and at the first year of life. Children were classified as exposed to antibiotics prenatally if the mother received at least one course of oral antibiotics during pregnancy and postnatally if the mother reported that the child received at least one oral antibiotic treatment during the first year of life. Outcomes included repeated weight, body mass index (BMI), waist circumference, body fat (%), total cholesterol and blood pressure. We applied mixed effects, linear and log-binomial regression models after adjusting for important covariates. RESULTS: Around 14.6% of the participating children were prenatally exposed to antibiotics and 32.4% received antibiotics during the first year of life. Prenatal exposure to antibiotics was associated with a twofold increase in the risk for obesity (risk ratio [RR]; 95% confidence interval [CI]: 2.09 [1.58, 2.76]) and abdominal obesity (RR [95% CI]: 2.56 [1.89, 3.47]) at 6 years. Postnatal exposure to antibiotics was associated with increased weight (beta [95% CI]: 00.25 [0.06, 0.44]) and BMI (beta [95% CI]: 0.23 [0.003, 0.45]) SD scores from 2 to 7 years of life. CONCLUSION: Early-life antibiotic use was associated with accelerated childhood growth and higher adiposity.

The longitudinal association of eating behaviour and ADHD symptoms in school age children: a follow-up study in the RHEA cohort.

Previous evidence suggests a link between attention deficit hyperactivity disorder (ADHD) symptoms and disordered eating behaviours; however, the direction of the causal association remains unclear. Building on our previous research, we aimed to examine the longitudinal association between eating behaviours at 4 years, ADHD symptoms at 6 years of age, and the role of body mass index (BMI). We included children from the RHEA mother-child cohort in Greece, followed up at 4 and 6 years (n = 926). Parents completed the Children's Eating Behaviour Questionnaire (CEBQ) to assess children's eating behaviour at 4 years and the ADHD Test (ADHDT) and Child Behaviour Checklist for ages 6-18 (CBCL/6-18) to evaluate ADHD symptoms at 4 and 6 years, respectively, as well as measures of BMI. Longitudinal structural equation modeling (SEM) was carried out to evaluate the associations of all variables between 4 and 6 years. Food responsiveness at 4 years was positively associated with hyperactivity at age 6, whereas emotional overeating was negatively associated with hyperactivity. There was no evidence of an association between eating behaviours of preschoolers and BMI at 6 years, or BMI at 4 years and later ADHD symptoms and vice versa. Findings suggest that food responsiveness is an early marker of ADHD symptoms at 6 years of age. In contrast to our hypothesis there was no significant association between ADHD at age 4 and BMI at age 6.

Exposure to Perfluoroalkyl Substances and Glucose Homeostasis in Youth.

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes. OBJECTIVE: We examined associations between PFAS exposure and glucose metabolism in youth. METHODS: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n=310) participated in annual visits for an average of 3.3±2.9y. Generalizability of findings were tested in young adults from the Southern California Children's Health Study (CHS; n=135) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and ß-cell function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography-high-resolution mass spectrometry; high levels were defined as concentrations >66th percentile. RESULTS: In females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels (≥2.0 ng/mL) were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had 25-mg/dL higher 60-min glucose (95% CI: 12, 39mg/dL; p<0.0001), 15-mg/dL higher 2-h glucose (95% CI: 1, 28mg/dL; p=0.04), and 25% lower ß-cell function (p=0.02) compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had 26-mg/dL higher 60-min glucose (95% CI: 6.0, 46mg/dL; p=0.01) and 19-mg/dL higher 2-h glucose, which did not meet statistical significance (95% CI: -1, 39mg/dL; p=0.08). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism. DISCUSSION: Youth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in ß-cell function. These associations appeared during puberty and were most pronounced postpuberty. https://doi.org/10.1289/EHP9200.

Associations of exposure to cadmium, antimony, lead and their mixture with gestational thyroid homeostasis.

Maintaining thyroid homeostasis during pregnancy is vital for fetal development. The few studies that have investigated associations between metal exposure and gestational thyroid function have yielded mixed findings. To evaluate the association of exposure to a mixture of toxic metals with thyroid parameters in 824 pregnant women from the Rhea birth cohort in Crete, Greece. Concentrations of three toxic metals [cadmium (Cd), antimony (Sb), lead (Pb)] and iodine were measured in urine using inductively coupled plasma mass spectrometry and thyroid hormones [Thyroid Stimulating Hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3)] were measured in serum in early pregnancy. Associations of individual metals with thyroid parameters were assessed using adjusted regression models, while associations of the metal mixture with thyroid parameters were assessed using Bayesian Kernel Machine Regression (BKMR).Women with high (3rd tertile) concentrations of urinary Cd, Sb and Pb, respectively, had 13.3 % (95%CI: 2.0 %, 23.2 %), 12.5 % (95%CI: 1.8 %, 22.0 %) and 16.0 % (95%CI: 5.7 %, 25.2 %) lower TSH compared to women with low concentrations (2nd and 1st tertile). In addition, women with high urinary Cd had 2.2 % (95%CI: 0.0 %, 4.4 %) higher fT4 and 4.0 % (95%CI: -0.1 %, 8.1 %) higher fT3 levels, and women with high urinary Pb had 4 % (95%CI: 0.2 %, 8.0 %) higher fT3 levels compared to women with low exposure. The negative association of Cd with TSH persisted only when iodine sufficiency was unfavorable. BKMR attested that simultaneous exposure to toxic metals was associated with decreased TSH and increased fT3 and revealed a potential synergistic interaction of Cd and Pb in association with TSH. The present results suggest that exposure to toxic metals even at low levels can alter gestational thyroid homeostasis.

Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

Heterogeneous associations of polyomaviruses and herpesviruses with allergy-related phenotypes in childhood.

BACKGROUND: Evidence suggests a complex interplay between infections and allergic diseases. OBJECTIVE: To explore the association of 14 common viruses with eczema, asthma, and rhinoconjunctivitis in childhood. METHODS: We used cross-sectional (n = 686) and prospective (n = 440) data from children participating in the Rhea birth cohort. Immunoglobulin G to polyomaviruses (BK polyomavirus, JC polyomavirus, KI polyomavirus [KIPyV], WU polyomavirus [WUPyV], human polyomavirus 6, human polyomavirus 7, Trichodysplasia spinulosa polyomavirus, Merkel cell polyomavirus, human polyomavirus 9, and human polyomavirus 10) and herpesviruses (Epstein-Barr virus, Cytomegalovirus, Herpes simplex virus-1, Herpes simplex virus-2) were measured at age 4 years by fluorescent bead-based multiplex serology. Definitions of eczema, asthma, and rhinoconjunctivitis at ages 4 and 6 years were based on questionnaires. Mediation of the associations by immune biomarkers was tested. RESULTS: Less likely to have eczema at age 4 years were KIPyV-seropositive (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.27-0.82) and human polyomavirus 6 (OR, 0.44; 95% CI, 0.26-0.73) compared with their seronegative counterparts. Seropositivity to Epstein-Barr virus was negatively associated with eczema at age 4 years (OR, 0.39; 95% CI, 0.22-0.67) and 6 years (OR, 0.50; 95% CI, 0.25-0.99). Children with a higher burden of herpesviruses or of skin polyomaviruses had the lowest odds of eczema at age 4 years. Higher odds for asthma at age 4 years were found for WUPyV-seropositive children (OR, 3.98; 95% CI, 1.38-11.51), and for children seropositive to both respiratory polyomaviruses (KIPyV and WUPyV) (OR, 7.35; 95% CI, 1.66-32.59) compared with children seronegative to both. No associations were observed for rhinoconjunctivitis. There was no evidence of mediation by immune biomarkers. CONCLUSION: A heterogeneous pattern of infections and allergic diseases was observed with common infections associated with a decreased eczema risk and an increased asthma risk in children.

In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. APPROACH AND RESULTS: We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 µg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL-1ß, IL-6, IL-8, and TNF-α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSIONS: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece.

BACKGROUND: Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. METHODS: The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection: 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at age 11, respectively. BKMR results were compared using static versus percentile-based cutoffs to define elevated BP. RESULTS: Molybdenum and lead were the mixture components most consistently associated with BP. J-shaped relationships were observed between molybdenum and both systolic and diastolic BP at age 4. Similar associations were identified for both molybdenum and lead in relation to elevated BP at age 11. For molybdenum concentrations above the inflection points (~ 40-80 µg/L), positive associations with BP at age 4 were stronger at high levels of lead. Lead was positively associated with BP measures at age 4, but only at high levels of molybdenum. Potential interactions between molybdenum and lead were also identified for BP at age 11, but were sensitive to the cutoffs used to define elevated BP. CONCLUSIONS: Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.

Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother-child cohort study in Crete, Greece.

BACKGROUND: Maternal thyroid hormones' supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid dysfunction with child neuropsychological development from infancy to early childhood. METHODS: We included 757 mother-child pairs from the prospective 'Rhea' cohort on Crete, Greece. Maternal thyroid functioning was assessed by quantitative analysis of serum thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies and thyroglobulin antibodies at early gestation (mean=14 weeks). Neuropsychological assessment was based on Bayley Scales of Infant Development (18 months of age), McCarthy Scales of Children's Abilities (4 years of age), Raven's Coloured Progressive Matrices, Trail Making Test and Finger Tapping Test (6 years of age). RESULTS: In multivariate adjusted linear regression analyses, maternal hypothyroxinemia was associated with decreased verbal scores at 4 years and reduced motor speed at 6 years of age. Maternal thyroid autoimmunity was associated with decreased child perceptual and motor ability at 4 years of age. Four trajectories of longitudinal non-verbal cognitive development were identified and children exposed to maternal thyroid autoimmunity had increased risk for belonging to an adverse trajectory ('low': adjusted relative risk ratio (RRR) = 2.7 95% CI: (1.4, 5.2), 'high-decreasing': adjusted RRR = 2.2 95% CI: (1.2, 4.0), 'low-increasing': adjusted RRR = 1.8 95% CI: (1.0, 3.2)). CONCLUSION: Maternal hypothyroxinemia is associated with reduced offspring verbal and motor ability. Maternal thyroid autoimmunity is associated with decreased offspring perceptual performance and motor ability and increased risk for adverse non-verbal cognitive development from infancy to childhood.

Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children.

BACKGROUND AND AIMS: Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure to PFAS associates with established serum biomarkers of liver injury and alterations in serum metabolome in children. APPROACH AND RESULTS: We used data from 1,105 mothers and their children (median age, 8.2 years; interquartile range, 6.6-9.1) from the European Human Early-Life Exposome cohort (consisting of six existing population-based birth cohorts in France, Greece, Lithuania, Norway, Spain, and the United Kingdom). We measured concentrations of perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane sulfonate, and perfluoroundecanoate in maternal blood. We assessed concentrations of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in child serum. Using Bayesian kernel machine regression, we found that higher exposure to PFAS during pregnancy was associated with higher liver enzyme levels in children. We also measured child serum metabolomics through a targeted assay and found significant perturbations in amino acid and glycerophospholipid metabolism associated with prenatal PFAS. A latent variable analysis identified a profile of children at high risk of liver injury (odds ratio, 1.56; 95% confidence interval, 1.21-1.92) that was characterized by high prenatal exposure to PFAS and increased serum levels of branched-chain amino acids (valine, leucine, and isoleucine), aromatic amino acids (tryptophan and phenylalanine), and glycerophospholipids (phosphatidylcholine [PC] aa C36:1 and Lyso-PC a C18:1). CONCLUSIONS: Developmental exposure to PFAS can contribute to pediatric liver injury.

Gestational sleep deprivation is associated with higher offspring body mass index and blood pressure.

STUDY OBJECTIVES: The objective of this study was to evaluate the association between gestational sleep deprivation and childhood adiposity and cardiometabolic profile. METHODS: Data were used from two population-based birth cohorts (Rhea study and Amsterdam Born Children and their Development study). A total of 3,608 pregnant women and their children were followed up until the age of 11 years. Gestational sleep deprivation was defined as 6 or fewer hours of sleep per day, reported by questionnaire. The primary outcomes included repeated measures of body mass index (BMI), waist circumference, body fat, serum lipids, systolic and diastolic blood pressure (DBP) levels in childhood. We performed a pooled analysis with adjusted linear mixed effect and Cox proportional hazards models. We tested for mediation by birthweight, gestational age, and gestational diabetes. RESULTS: Gestational sleep deprivation was associated with higher BMI (beta; 95% CI: 0.7; 0.4, 1.0 kg/m2) and waist circumference (beta; 95% CI: 0.9; 0.1, 1.6 cm) in childhood, and increased risk for overweight or obesity (HR; 95% CI: 1.4; 1.1, 2.0). Gestational sleep deprivation was also associated with higher offspring DBP (beta; 95% CI: 1.6; 0.5, 2.7 mmHg). The observed associations were modified by sex (all p-values for interaction < 0.05); and were more pronounced in girls. Gestational diabetes and shorter gestational age partly mediated the seen associations. CONCLUSIONS: This is the first study showing that gestational sleep deprivation may increase offspring's adiposity and blood pressure, while exploring possible mechanisms. Attention to glucose metabolism and preterm birth might be extra warranted in mothers with gestational sleep deprivation.