Placental mitochondrial DNA content is associated with childhood intelligence

Background: Developmental processes in the placenta and the fetal brain are shaped by the similar biological signals. Evidence accumulates that adaptive responses of the placenta may influence central nervous system development. We hypothesize that placental mtDNA content at birth is associated with intelligence in childhood. In addition, we investigate if intra-pair differences in mtDNA content are associated with intra-pair differences in intelligence. Methods: Relative mtDNA content was measured using qPCR in placental tissue of 375 children of the East Flanders Prospective Twin Survey. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) between 8 and 15 years old. We accounted for sex, gestational age, birth weight, birth year, zygosity and chorionicity, cord insertion, age at measurement, indicators of socioeconomic status, smoking during pregnancy, and urban environment. Results: In multivariable adjusted mixed modelling analysis, each doubling in placental mtDNA content was associated with 2.0 points (95% CI 0.02 to 3.9; p = 0.05) higher total and 2.3 points (95% CI 0.2 to 4.3; p = 0.03) higher performance IQ in childhood. We observed no association between mtDNA content and verbal intelligence. Intra-pair differences in mtDNA content and IQ were significantly (p = 0.01) correlated in monozygotic-monochorionic twin pairs, showing that the twin with the highest mtDNA content was 1.9 times more likely (p = 0.05) to have the highest IQ. This was not observed in dichorionic twin pairs. Conclusions: We provide the first evidence that placental mtDNA content is associated with childhood intelligence. This emphasizes the importance of placental mitochondrial function during in utero life on fetal brain development with long-lasting consequences

Host and environmental predictors of exhaled breath temperature in the elderly

BACKGROUND: Exhaled breath temperature has been suggested as a new method to detect and monitor pathological processes in the respiratory system. The putative mechanism of this approach is based upon changes in the blood flow. So far potential factors that influence breath temperature have not been studied in the general population. METHODS: The exhaled breath temperature was measured in 151 healthy non-smoking elderly (aged: 60–80 years) at room temperature with the X-halo device with an accuracy of 0.03°C. We related exhaled breath temperature by use of regression models with potential predictors including: host factors (sex, age) and environmental factors (BMI, physical activity, and traffic indicators). RESULTS: Exhaled breath temperature was lower in women than in men and was inversely associated with age, physical activity. BMI and daily average ambient temperature were positively associated with exhaled breath temperature. Independent of the aforementioned covariates, exhaled breath temperature was significantly associated with several traffic indicators. Residential proximity to major road was inversely associated with exhaled breath temperature: doubling the distance to the nearest major intense road was observed a decrease of 0.17°C (95% CI: -0.33 to -0.01; p = 0.036). CONCLUSIONS: Exhaled breath temperature has been suggested as a noninvasive method for the evaluation of airway inflammation. We provide evidence that several factors known to be involved in proinflammatory conditions including BMI, physical activity and residential proximity to traffic affect exhaled breath temperature. In addition, we identified potential confounders that should be taken into account in clinical and epidemiological studies on exhaled breath temperature including sex, age, and ambient temperature

Residential green space and child intelligence and behavior across urban, suburban, and rural areas in Belgium: A longitudinal birth cohort study of twins.

BACKGROUND:Exposure to green space has beneficial effects on several cognitive and behavioral aspects. However, to our knowledge, no study addressed intelligence as outcome. We investigated whether the level of urbanicity can modify the association of residential green space with intelligence and behavior in children. METHODS AND FINDINGS:This study includes 620 children and is part of the East Flanders Prospective Twin Survey (EFPTS), a registry of multiple births in the province of East Flanders, Belgium. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) in 620 children (310 twin pairs) between 7 and 15 years old. From a subset of 442 children, behavior was determined based on the Achenbach Child Behavior Checklist (CBCL). Prenatal and childhood residential addresses were geocoded and used to assign green space indicators. Mixed modeling was performed to investigate green space in association with intelligence and behavior while adjusting for potential confounding factors including sex, age, parental education, neighborhood household income, year of assessment, and zygosity and chorionicity. We found that residential green space in association with both intelligence and behavior in children was modified by the degree of urbanicity (p < 0.001). In children living in an urban environment, multivariable adjusted mixed modeling analysis revealed that an IQR increment of residential green space (3,000-m radius) was associated with a 2.6 points (95% CI 1.4-3.9; p < 0.001) higher total intelligence quotient (IQ) and 2.0 points (95% CI -3.5 to -0.4; p = 0.017) lower externalizing behavioral score. In children residing in a rural or suburban environment, no association was found. A limitation of this study is that no information was available on school location and the potential for unmeasured confounding (e.g., time spend outdoors). CONCLUSIONS:Our results indicate that residential green space may be beneficial for the intellectual and the behavioral development of children living in urban areas. These findings are relevant for policy makers and urban planners to create an optimal environment for children to develop their full potential

Mortality related to cold and heat. What do we learn from dairy cattle?

Extreme temperatures are associated with increased mortality among humans. Because similar epidemiologic studies in animals may add to the existing evidence, we investigated the association between ambient temperature and the risk of mortality among dairy cattle. We used data on 87,108 dairy cow deaths in Belgium from 2006 to 2009, and we combined a case-crossover design with distributed lag non-linear models. Province-specific results were combined in a multivariate meta-analysis. Relative to the estimated minimum mortality temperature of 15.4°C (75th percentile), the pooled cumulative relative risks over lag 0-25 days were 1.26 (95% CI: 1.11, 1.42) for extreme cold (1st percentile, -3.5°C), 1.35 (95% CI: 1.19, 1.54) for moderate cold (5th percentile, -0.3°C), 1.09 (95% CI: 1.02, 1.17) for moderate heat (95th percentile, 19.7°C), and 1.26 (95% CI: 1.08; 1.48) for extreme heat (99th percentile, 22.6°C). The temporal pattern of the temperature-mortality association was similar to that observed in humans, i.e. acute effects of heat and delayed and prolonged effects of cold. Seasonal analyses suggested that most of the temperature-related mortality, including cold effects, occurred in the warm season. Our study reinforces the evidence on the plausibility of causal effects in humans.publisher: Elsevier articletitle: Mortality related to cold and heat. What do we learn from dairy cattle? journaltitle: Environmental Research articlelink: http://dx.doi.org/10.1016/j.envres.2016.05.018 content_type: article copyright: © 2016 Published by Elsevier Inc.status: publishe

A multi-exposure approach to study telomere dynamics in childhood : a role for residential green space and waist circumference

Background: Telomeres are vulnerable to various environmental exposures and lifestyle factors, encompassed in the exposome. Recent research shows that telomere length is substantially determined early in life and that exposures in childhood may have important consequences in setting later life telomere length. Objectives: We explore in a child population the associations of 17 exposures with telomere length and longitudinal telomere change. Methods: Children (2.8-10.3y at baseline, 51.3% boys) were followed-up for five to seven years. Relative telomere length was measured at baseline and follow-up using quantitative real-time PCR. Exposures and lifestyle factors included: body composition (body mass index and waist circumference), dietary habits (sugar- and fat-rich food intake, vegetables and fruit intake), psychosocial stress (events, emotions, behaviour), sleep duration, physical activity, and residential environmental quality (longterm black carbon, particulate matter exposure, and residential green space). Cross-sectional (n=182) and longitudinal (n=150) analyses were assessed using linear regression models, adjusting for age, sex, socioeconomic status and multiple testing. Results: Our longitudinal analyses showed that higher residential green space at baseline was associated with (beta = 0.261, p=0.002) lower telomere attrition and that children with a higher waist circumference at baseline showed a higher telomere attrition (beta = - 0.287, p=0.001). These two predictors were confirmed via LASSO variable selection and correction for multiple testing. In addition, children with more unhealthy exposures at baseline had a significantly higher telomere attrition over the follow-up period compared to children with more healthy exposures (beta = - 0.200, p=0.017). Discussion: Waist circumference and residential green space were identified as predictors associated with telomere attrition in childhood. These results further support the advantages of a healthy lifestyle from early age onwards and the importance of a green environment to promote molecular longevity from childhood onwards

Newborn telomere length predicts later life telomere length: Tracking telomere length from birth to child- and adulthood

Background Telomere length (TL) is considered a biological marker of aging and may indicate age-related disease susceptibility. Adults and children show a fixed ranking and tracking of TL over time. However, the contribution of an individual's initial birth TL to their later life TL is unknown. We evaluated change and tracking of TL from birth to child- and adulthood. Methods Telomere length at birth was measured using qPCR in two independent prospective birth cohorts. After a median follow-up period of 4 years in ENVIRONAGE (n = 273) we assessed leukocyte telomere length (LTL) and after 23 years in EFPTS (n = 164) buccal TL was assessed. Correlations and multivariable regression models were applied to study telomere tracking and determinants of TL change from birth onwards. Findings In children, LTL at the age of 4 correlates with TL at the start of life both in cord blood (r = 0.71, P < 0.0001;) and placenta (r = 0.60, P < 0.0001) and was –11.2% and –33.1% shorter, respectively. In adulthood, buccal TL at the age of 23 correlates with placental TL (r = 0.46, P < 0.0001) and was –35.9% shorter. TL attrition was higher in individuals with longer birth TL. However, based on TL ranking, individuals do not tend to change dramatically from TL rank after 4 or 23 years of follow-up. Finally, longer maternal TL associates with lower telomere attrition in the next generation. Interpretation The high prediction of newborn TL for later life TL, and stable TL ranking from birth onwards underscores the importance of understanding the initial setting of newborn TL and its significance for later life

Birth outcomes of twins after multifetal pregnancy reduction compared with primary twins

BACKGROUND: The introduction of assisted reproductive technology and the trend of increasing maternal age at conception have contributed to a significant rise in the incidence of multiple pregnancies. Multiple pregnancies bear several inherent risks for both mother and child. These risks increase with plurality and type of chorionicity. Multifetal pregnancy reduction is the selective abortion of ≥1 fetuses to improve the outcome of the remaining fetus(es) by decreasing the risk of premature birth and other complications. OBJECTIVE: This study aimed to compare birth outcomes of trichorionic triplets reduced to twins with those of trichorionic triplets and primary dichorionic twins. The added value of this study is the comparison with an additional control group, namely primary dichorionic twins. STUDY DESIGN: This was a retrospective cohort study. Data from January 1990 to November 2016 were collected from the East Flanders Prospective Twin Survey, one of the largest European multiple birth registries. A total of 85 trichorionic triplet pregnancies (170 neonates) undergoing multifetal pregnancy reduction to twins were compared with 5093 primary dichorionic twin pregnancies (10,186 neonates) and 104 expectantly managed trichorionic triplet pregnancies (309 neonates). The assessed outcomes were gestational age at delivery, birthweight, and small for gestational age. RESULTS: Pregnancy reduction from triplets to twins was associated with higher birthweight (+365.44 g; 95% confidence interval, 222.75–508.14 g; P&lt;.0001) and higher gestational age (1.7 weeks; 95% confidence interval, 0.93–2.46; P&lt;.0001) compared with ongoing trichorionic triplets after adjustment for sex, parity, method of conception, birth year, and maternal age. A trend toward lower risk of small for gestational age was observed. Reduced triplets had, on average, lower birthweight (−263.12 g; 95% confidence interval, −371.80 to −154.44 g; P&lt;.0001) and lower gestational age (−1.13 weeks; 95% confidence interval, −1.70 to −0.56; P=.0001) compared with primary twins. No statistically significant difference was observed between primary twins and reduced triplets that reached 32 weeks of gestation. CONCLUSION: Multifetal pregnancy reduction from trichorionic triplets to twins significantly improved birth outcomes. This suggests that multifetal pregnancy reduction of trichorionic triplets to twins is medically justifiable. However, the birth outcomes of primary twins before 32 weeks of gestation are still better than those of reduced triplets. The process of multifetal pregnancy reduction includes at least 1 fetal death by definition, and thus prevention of higher-order pregnancies is preferable.</p

Residential green space and waist circumference affect telomere shortening in childhood: the longitudinal ChiBS study

BACKGROUND: Telomere shortening, recognised as one of the most well known biomarkers of biological ageing, is susceptible to various environmental and lifestyle factors, encompassed in the exposome. Research shows that telomere length is substantially determined early in life and that exposures in childhood can have important consequences in setting telomere length later in life and thus the lifespan of an individual. We explored the associations between 17 exposures and longitudinal telomere change in a child population. METHODS: Children up to the age of 9 years, from Aalter, Belgium, were enrolled in 2008 and 2010 and followed-up for 5 or 7 years (up to 2015). Relative telomere length was measured at baseline (2008 or 2010) and at follow-up, in 2015, through quantitative real-time PCR. Exposures and lifestyle factors comprised: body-mass index, waist circumference, dietary habits (ie, sugar-rich and fat-rich food intake and vegetables and fruit intake), psychosocial stress (ie, negative events, emotions, and behaviour), sleep duration, physical activity, and residential environmental quality (long-term black carbon and particulate matter exposure and residential green space). Green space was estimated from high-resolution land cover data within several buffers (50-3000 m) around the child's residence. Cross-sectional and longitudinal analyses were done by means of linear regression models, adjusting for length of follow-up, age, sex, and socioeconomic status. Effect size was expressed as β, the standardised regression coefficient of the linear regression, and was calculated by multiplying the unstandardised regression coefficient by the standard deviation of the predictor variable and dividing by the standard deviation of the outcome variable. Written informed consent was obtained from all parents. Children aged 12 years and older also provided written informed consent. Children younger than 12 years gave verbal consent. FINDINGS: 150 children (77 [51%] boys and 73 [49%] girls) aged 2·8-10·3 years (median 5·9 years [IQR 4·9-7·1]) at baseline were included in the longitudinal analysis, which showed that higher residential green space at baseline was associated with inferior telomere shortening (β=0·261; p=0·0018), whereas a higher baseline waist circumference was associated with more telomere attrition (β=-0·287; p=0·0015). These predictors were confirmed via lasso variable selection and correction for multiple testing. In addition, children with more unhealthy exposures had significantly more telomere shortening over the follow-up period than did children with less unhealthy baseline exposures (β=-0·200; p=0·017). INTERPRETATION: Residential green space and waist circumference were identified as predictors of telomere shortening in childhood. These results further showcase the benefits of a healthy lifestyle from an early age and the importance of a green environment in promoting molecular longevity from childhood onwards. FUNDING: Research Foundation Flanders (Brussels, Belgium; project number G073315N)