Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of four regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case (CC) analysis and multiple imputation (MI) in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the UK. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with CC analysis or MI. We showed that RC methods resulted in more accurate estimation of the relation between mobile phone use and health outcomes, by combining self-reported data with objective operator-recorded data available for a subset of participants.

Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom.

Headache is a common condition with a substantial burden of disease worldwide. Concerns have been raised over the potential impact of long-term mobile phone use on headache due to radiofrequency electromagnetic fields (RF-EMFs). We explored prospectively the association between mobile phone use at baseline (2009-2012) and headache at follow-up (2015-2018) by analysing pooled data consisting of the Dutch and UK cohorts of the Cohort Study of Mobile Phone Use and Health (COSMOS) (N = 78,437). Frequency of headache, migraine, and information on mobile phone use, including use of hands-free devices and frequency of texting, were self-reported. We collected objective operator data to obtain regression calibrated estimates of voice call duration. In the model mutually adjusted for call-time and text messaging, participants in the high category of call-time showed an adjusted odds ratio (OR) of 1.04 (95 % CI: 0.94-1.15), with no clear trend of reporting headache with increasing call-time. However, we found an increased risk of weekly headache (OR = 1.40, 95 % CI: 1.25-1.56) in the high category of text messaging, with a clear increase in reporting headache with increasing texting. Due to the negligible exposure to RF-EMFs from texting, our results suggest that mechanisms other than RF-EMFs are responsible for the increased risk of headache that we found among mobile phone users.

A UK framework for the assessment and integration of different scientific evidence streams in chemical risk assessment.

BACKGROUND: Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation. METHODS/APPROACH: All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation. A qualitative estimate of the probability of causation is plotted for each line of evidence and a combined estimate provided. DISCUSSION/CONCLUSIONS: Guidance is provided on integration of multiple lines of evidence for causation, based on current best practice. Qualitative estimates of probability for each line of evidence are plotted graphically. This ensures a deliberative, consensus conclusion on likelihood of causation is reached. It also ensures clear communication of the influence of the different lines of evidence on the overall conclusion on causality. Issues on which advice from the respective Committees is sought varies considerably, hence the guidance is designed to be sufficiently flexible to meet this need.

Depression and Anxiety in Adolescents During the COVID-19 Pandemic in Relation to the Use of Digital Technologies: Longitudinal Cohort Study.

BACKGROUND: Adolescents are susceptible to mental illness and have experienced substantial disruption owing to the COVID-19 pandemic. The digital environment is increasingly important in the context of a pandemic when in-person social connection is restricted. OBJECTIVE: This study aims to estimate whether depression and anxiety had worsened compared with the prepandemic period and examine potential associations with sociodemographic characteristics and behavioral factors, particularly digital behaviors. METHODS: We analyzed cross-sectional and longitudinal data from a large, representative Greater London adolescent cohort study: the Study of Cognition, Adolescents and Mobile Phones (SCAMP). Participants completed surveys at T1 between November 2016 and July 2018 (N=4978; aged 13 to 15 years) and at T2 between July 2020 and June 2021 (N=1328; aged 16 to 18 years). Depression and anxiety were measured using the Patient Health Questionnaire and Generalized Anxiety Disorder scale, respectively. Information on the duration of total mobile phone use, social network site use, and video gaming was also collected using questionnaires. Multivariable logistic regression was used to assess the cross-sectional and longitudinal associations of sociodemographic characteristics, digital technology use, and sleep duration with clinically significant depression and anxiety. RESULTS: The proportion of adolescents who had clinical depression and anxiety significantly increased at T2 (depression: 140/421, 33.3%; anxiety: 125/425, 29.4%) compared with the proportion of adolescents at T1 (depression: 57/421, 13.5%; anxiety: 58/425, 13.6%; P for 2-proportion z test <.001 for both depression and anxiety). Depression and anxiety levels were similar between the summer holiday, school opening, and school closures. Female participants had higher odds of new incident depression (odds ratio [OR] 2.5, 95% CI 1.5-4.18) and anxiety (OR 2.11, 95% CI 1.23-3.61) at T2. A high level of total mobile phone use at T1 was associated with developing depression at T2 (OR 1.89, 95% CI 1.02-3.49). Social network site use was associated with depression and anxiety cross-sectionally at T1 and T2 but did not appear to be associated with developing depression or anxiety longitudinally. Insufficient sleep at T1 was associated with developing depression at T2 (OR 2.26, 95% CI 1.31-3.91). CONCLUSIONS: The mental health of this large sample of adolescents from London deteriorated during the pandemic without noticeable variations relating to public health measures. The deterioration was exacerbated in girls, those with preexisting high total mobile phone use, and those with preexisting disrupted sleep. Our findings suggest the necessity for allocating resources to address these modifiable factors and target high-risk groups.

Risk clustering and psychopathology from a multi-center cohort of Indian children, adolescents, and young adults.

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

Spatial modelling and inequalities of environmental noise in Accra, Ghana.

Noise pollution is a growing environmental health concern in rapidly urbanizing sub-Saharan African (SSA) cities. However, limited city-wide data constitutes a major barrier to investigating health impacts as well as implementing environmental policy in this growing population. As such, in this first of its kind study in West Africa, we measured, modelled and predicted environmental noise across the Greater Accra Metropolitan Area (GAMA) in Ghana, and evaluated inequalities in exposures by socioeconomic factors. Specifically, we measured environmental noise at 146 locations with weekly (n = 136 locations) and yearlong monitoring (n = 10 locations). We combined these data with geospatial and meteorological predictor variables to develop high-resolution land use regression (LUR) models to predict annual average noise levels (LAeq24hr, Lden, Lday, Lnight). The final LUR models were selected with a forward stepwise procedure and performance was evaluated with cross-validation. We spatially joined model predictions with national census data to estimate population levels of, and potential socioeconomic inequalities in, noise levels at the census enumeration-area level. Variables representing road-traffic and vegetation explained the most variation in noise levels at each site. Predicted day-evening-night (Lden) noise levels were highest in the city-center (Accra Metropolis) (median: 64.0 dBA) and near major roads (median: 68.5 dBA). In the Accra Metropolis, almost the entire population lived in areas where predicted Lden and night-time noise (Lnight) surpassed World Health Organization guidelines for road-traffic noise (Lden <53; and Lnight <45). The poorest areas in Accra also had significantly higher median Lden and Lnight compared with the wealthiest ones, with a difference of ∼5 dBA. The models can support environmental epidemiological studies, burden of disease assessments, and policies and interventions that address underlying causes of noise exposure inequalities within Accra.

Personal radiofrequency electromagnetic field exposure of adolescents in the Greater London area in the SCAMP cohort and the association with restrictions on permitted use of mobile communication technologies at school and at home.

Personal measurements of radiofrequency electromagnetic fields (RF-EMF) have been used in several studies to characterise personal exposure in daily life, but such data are limitedly available for adolescents, and not yet for the United Kingdom (UK). In this study, we aimed to characterise personal exposure to RF-EMF in adolescents and to study the association between exposure and rules applied at school and at home to restrict wireless communication use, likely implemented to reduce other effects of mobile technology (e.g. distraction). We measured exposure to RF-EMF for 16 common frequency bands (87.5 MHz-3.5 GHz), using portable measurement devices (ExpoM-RF), in a subsample of adolescents participating in the cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP) from Greater London (UK) (n = 188). School and home rules were assessed by questionnaire and concerned the school's availability of WiFi and mobile phone policy, and parental restrictions on permitted mobile phone use. Adolescents recorded their activities in real time using a diary app on a study smartphone, while characterizing their personal RF-EMF exposure in daily life, during different activities and times of the day. Data analysis was done for 148 adolescents from 29 schools who recorded RF-EMF data for a median duration of 47 h. The majority (74%) of adolescents spent part of their time at school during the measurement period. Median total RF-EMF exposure was 40 µW/m2 at home, 94 µW/m2 at school, and 100 µW/m2 overall. In general, restrictions at school or at home made little difference for adolescents' measured exposure to RF-EMF, except for uplink exposure from mobile phones while at school, which was found to be significantly lower for adolescents attending schools not permitting phone use at all, compared to adolescents attending schools allowing mobile phone use during breaks. This difference was not statistically significant for total personal exposure. Total exposure to RF-EMF in adolescents living in Greater London tended to be higher compared to exposure levels reported in other European countries. This study suggests that school policies and parental restrictions are not associated with a lower RF-EMF exposure in adolescents.

Impact of mobile phones and wireless devices use on children and adolescents' mental health: a systematic review.

Growing use of mobiles phones (MP) and other wireless devices (WD) has raised concerns about their possible effects on children and adolescents' wellbeing. Understanding whether these technologies affect children and adolescents' mental health in positive or detrimental ways has become more urgent following further increase in use since the COVID-19 outbreak. To review the empirical evidence on associations between use of MP/WD and mental health in children and adolescents. A systematic review of literature was carried out on Medline, Embase and PsycINFO for studies published prior to July 15th 2019, PROSPERO ID: CRD42019146750. 25 observational studies published between January 1st 2011 and 2019 were reviewed (ten were cohort studies, 15 were cross-sectional). Overall estimated participant mean age and proportion female were 14.6 years and 47%, respectively. Substantial between-study heterogeneity in design and measurement of MP/WD usage and mental health outcomes limited our ability to infer general conclusions. Observed effects differed depending on time and type of MP/WD usage. We found suggestive but limited evidence that greater use of MP/WD may be associated with poorer mental health in children and adolescents. Risk of bias was rated as 'high' for 16 studies, 'moderate' for five studies and 'low' for four studies. More high-quality longitudinal studies and mechanistic research are needed to clarify the role of sleep and of type of MP/WD use (e.g. social media) on mental health trajectories in children and adolescents.

Adolescents' thoughts and feelings about the local and global environment: a qualitative interview study.

BACKGROUND: Despite a recent increase in engagement with environmental issues among young people, their impact upon adolescent mental health and wellbeing is not yet fully understood. Therefore, this study aimed to explore adolescents' thoughts and feelings about current environmental issues. METHODS: Semi-structured interviews were conducted with a convenience sample of 15 UK-based adolescents aged 14-18 years (66.7% female). Transcripts were inductively thematically analysed by the interviewing researcher and two adolescent co-researchers, with priority given to the co-researchers' impressions to strengthen interpretations of the personal experiences of the interviewees. RESULTS: Six themes were identified: the local environment, efficacy, challenging emotions, information, hindrances and perceptions of the future. The local environment was found to affect adolescents positively and negatively. Factors including greenspace and fresh air had a positive impact, and factors including noise and litter had a negative impact. Most participants reported feeling disempowered to personally influence environmental problems but were engaged with them and felt that trying to make a difference was beneficial for their wellbeing. Adolescents largely reported negative expectations about the environment's future. CONCLUSION: The UK adolescents interviewed appeared to be very engaged and emotionally affected by a perceived lack of care towards the environment, locally and globally. It is therefore imperative to amplify young people's voices and involve them in influencing environmental policy, for the benefit of young people and the planet. Further research should quantify the extent to which environmental issues affect young people's mental health and identify factors that could prevent or alleviate distress.

Modulatory effects of SES and multilinguistic experience on cognitive development: a longitudinal data analysis of multilingual and monolingual adolescents from the SCAMP cohort.

Previous research has shown that cognitive development is sensitive to socio-economic status (SES) and multilinguistic experiences. However, these effects are difficult to disentangle and SES may modulate the effects of multilingualism. The present study used data from a large cohort of pupils who took part in the Study of Cognition, Adolescents and Mobile Phones (SCAMP) at ages 11-12 (T1) and 13-15 years old (T2). Cognitive measures were derived from tasks of cognitive flexibility, verbal, spatial and visuo-spatial working memory, speech processing and non-verbal reasoning. Using SES information collected through questionnaires (school type, level of deprivation, parental education and occupation), the sample was clustered into high/medium/low SES groups. Comparisons focused on 517 monolingual and 329 multilingual pupils in the high/low SES groups. Having controlled for multiple comparisons, the results indicated a significant beneficial effect of bilingualism in measures of working memory, visuo-spatial processing and non-verbal reasoning. These effects were present in both high and low SES individuals and sustained at both times of development, with a particularly significant improvement of working memory abilities in low SES bilinguals at T2 as compared to monolingual peers. Theoretical and practical implications of these findings are considered and guidance for educators is discussed.

The Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA): an accelerated longitudinal cohort of children and adolescents in India.

The global burden of disease attributable to externalizing disorders such as alcohol misuse calls urgently for effective prevention and intervention. As our current knowledge is mainly derived from high-income countries such in Europe and North-America, it is difficult to address the wider socio-cultural, psychosocial context, and genetic factors in which risk and resilience are embedded in low- and medium-income countries. c-VEDA was established as the first and largest India-based multi-site cohort investigating the vulnerabilities for the development of externalizing disorders, addictions, and other mental health problems. Using a harmonised data collection plan coordinated with multiple cohorts in China, USA, and Europe, baseline data were collected from seven study sites between November 2016 and May 2019. Nine thousand and ten participants between the ages of 6 and 23 were assessed during this time, amongst which 1278 participants underwent more intensive assessments including MRI scans. Both waves of follow-ups have started according to the accelerated cohort structure with planned missingness design. Here, we present descriptive statistics on several key domains of assessments, and the full baseline dataset will be made accessible for researchers outside the consortium in September 2019. More details can be found on our website [cveda.org].

Digital Technology Use and BMI: Evidence From a Cross-sectional Analysis of an Adolescent Cohort Study.

BACKGROUND: The use of digital technology such as mobile phones is ubiquitous in adolescents. However, excessive use may have adverse health effects, possibly partially mediated by disruptions to sleep. OBJECTIVE: This study aims to assess the social predictors of digital technology use and their cross-sectional association with BMI z scores and being overweight in a large sample of adolescents. METHODS: We used baseline data from a subset of a large adolescent cohort from 39 schools across Greater London who participated in the Study of Cognition, Adolescents and Mobile Phones (n=1473). Digital technology use included phone calls, internet use on mobile phones, and video gaming on any device. Multilevel regression was used to assess the associations between digital technology use and age-specific and sex-specific BMI z scores and being overweight (including obesity). Measurements were derived from height and weight, obtained by the Tanita BC-418 Body Composition Analyzer. We examined whether these associations were mediated by insufficient sleep. RESULTS: Generally, participants with lower socioeconomic status reported more use of digital technology. Controlling for socioeconomic status, internet use on mobile phones for more than 3 hours per day was associated with higher BMI z scores (adjusted ß=.30, 95% CI 0.11-0.48) and greater odds of being overweight (adjusted odds ratio 1.60, 95% CI 1.09-2.34), compared with low use (≤30 minutes). Similar associations were found between video gaming and BMI z scores and being overweight. The BMI z score was more strongly related to weekday digital technology use (internet use on mobile phones and video gaming) than weekend use. Insufficient sleep partly mediated the associations between digital technology use and BMI z scores (proportion of mediation from 8.6% to 17.8%) by an indirect effect. CONCLUSIONS: We found an association between digital technology use and BMI in adolescents, partly mediated by insufficient sleep, suggesting that the underlying mechanisms may be multifactorial. Further research with longitudinal data is essential to explore the direction of the relationships.

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA): A developmental cohort study protocol.

BACKGROUND: Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders. METHODS: cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively. DISCUSSION: The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

Urine Metabolic Signatures of Multiple Environmental Pollutants in Pregnant Women: An Exposome Approach.

Exposure to environmental pollutants, particularly during pregnancy, can have adverse consequences on child development but little is known about the effects of pollutant mixtures on endogenous metabolism in pregnant women. We aimed to identify urinary metabolic signatures associated with low level exposure to multiple environmental pollutants in pregnant women from the INMA (INfancia y Medio Ambiente) birth cohort (Spain, N = 750). 35 chemical exposures were quantified in first trimester blood samples (organochlorine pesticides, PCBs, PFAS), in cord blood (mercury), and twice in urine at 12 and 32 weeks of pregnancy (metals, phthalates, bisphenol A). 1H nuclear magnetic resonance (NMR) metabolic profiles of urine were acquired in the same samples as pollutants. We explored associations between exposures and metabolism through an exposome-metabolome wide association scan and multivariate O2PLS modeling. Novel and reproducible associations were found across two periods of pregnancy for three nonpersistent pollutants and across two subcohorts for four of the persistent pollutants. We found novel metabolic signatures associated with arsenic exposure: TMAO and dimethylamine possibly related to gut microbial methylamine metabolism and homarine related to fish intake. Tobacco smoke exposure was related to coffee metabolism and PCBs with 3-hydroxyvaleric acid, usually released under ketoacidosis. These findings will have implications for further understanding of maternal-fetal health, and health across the life-course.

Total recall in the SCAMP cohort: Validation of self-reported mobile phone use in the smartphone era.

Mobile phone use, predominantly smartphones, is almost ubiquitous amongst both adults and children. However adults and children have different usage patterns. A major challenge with research on mobile phone use is the reliability of self-reported phone activity for accurate exposure assessment. We investigated the agreement between self-reported mobile phone use data and objective mobile operator traffic data in a subset of adolescents aged 11-12 years participating in the Study of Cognition, Adolescents and Mobile Phones (SCAMP) cohort. We examined self-reported mobile phone use, including call frequency, cumulative call time duration and text messages sent among adolescents from SCAMP and matched these data with records provided by mobile network operators (n = 350). The extent of agreement between self-reported mobile phone use and mobile operator traffic data use was evaluated using Cohen's weighted Kappa (ĸ) statistics. Sensitivity and specificity of self-reported low (< 1 call/day, ≤ 5min of call/day or ≤ 5 text messages sent/day) and high (≥ 11 calls/day, > 30min of call/day or ≥ 11 text messages sent /day) use were estimated. Agreement between self-reported mobile phone use and mobile operator traffic data was highest for the duration spent talking on mobile phones per day on weekdays (38.9%) and weekends (29.4%) compared to frequency of calls and number of text messages sent. Adolescents overestimated their mobile phone use during weekends compared to weekdays. Analysis of agreement showed little difference overall between the sexes and socio-economic groups. Weighted kappa between self-reported and mobile operator traffic data for call frequency during weekdays was κ = 0.12, 95% CI 0.06-0.18. Of the three modes of mobile phone use measured in the questionnaire, call frequency was the most sensitive for low mobile phone users on weekdays and weekends (77.1, 95% CI: 69.3-83.7 and 72.0, 95% CI: 65.0-78.4, respectively). Specificity was moderate to high for high users with the highest for call frequency during weekdays (98.4, 95% CI: 96.4-99.5). Despite differential agreement between adolescents' self-reported mobile phone use and mobile operator traffic data, our findings demonstrate that self-reported usage adequately distinguishes between high and low use. The greater use of mobile smartphones over Wi-Fi networks by adolescents, as opposed to mobile phone networks, means operator data are not the gold standard for exposure assessment in this age group. This has important implications for epidemiologic research on the health effects of mobile phone use in adolescents.

Estimating Particulate Exposure from Modern Municipal Waste Incinerators in Great Britain.

Municipal Waste Incineration (MWI) is regulated through the European Union Directive on Industrial Emissions (IED), but there is ongoing public concern regarding potential hazards to health. Using dispersion modeling, we estimated spatial variability in PM10 concentrations arising from MWIs at postcodes (average 12 households) within 10 km of MWIs in Great Britain (GB) in 2003-2010. We also investigated change points in PM10 emissions in relation to introduction of EU Waste Incineration Directive (EU-WID) (subsequently transposed into IED) and correlations of PM10 with SO2, NOx, heavy metals, polychlorinated dibenzo-p-dioxins/furan (PCDD/F), polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) emissions. Yearly average modeled PM10 concentrations were 1.00 × 10-5 to 5.53 × 10-2 µg m-3, a small contribution to ambient background levels which were typically 6.59-2.68 × 101 µg m-3, 3-5 orders of magnitude higher. While low, concentration surfaces are likely to represent a spatial proxy of other relevant pollutants. There were statistically significant correlations between PM10 and heavy metal compounds (other heavy metals (r = 0.43, p = <0.001)), PAHs (r = 0.20, p = 0.050), and PCBs (r = 0.19, p = 0.022). No clear change points were detected following EU-WID implementation, possibly as incinerators were operating to EU-WID standards before the implementation date. Results will be used in an epidemiological analysis examining potential associations between MWIs and health outcomes.

Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study.

BACKGROUND: Maternal metabolism during pregnancy is a major determinant of the intra-uterine environment and fetal outcomes. Herein, we characterize the maternal urinary metabolome throughout pregnancy to identify maternal metabolic signatures of fetal growth in two subcohorts and explain potential sources of variation in metabolic profiles based on lifestyle and clinical data. METHODS: We used 1H nuclear magnetic resonance (NMR) spectroscopy to characterize maternal urine samples collected in the INMA birth cohort at the first (n = 412 and n = 394, respectively, in Gipuzkoa and Sabadell cohorts) and third trimesters of gestation (n = 417 and 469). Metabolic phenotypes that reflected longitudinal intra- and inter-individual variation were used to predict measures of fetal growth and birth weight. RESULTS: A metabolic shift between the first and third trimesters of gestation was characterized by 1H NMR signals arising predominantly from steroid by-products. We identified 10 significant and reproducible metabolic associations in the third trimester with estimated fetal, birth, and placental weight in two independent subcohorts. These included branched-chain amino acids; isoleucine, valine, leucine, alanine and 3 hydroxyisobutyrate (metabolite of valine), which were associated with a significant fetal weight increase at week 34 of up to 2.4 % in Gipuzkoa (P < 0.005) and 1 % in Sabadell (P < 0.05). Other metabolites included pregnancy-related hormone by-products of estrogens and progesterone, and the methyl donor choline. We could explain a total of 48-53 % of the total variance in birth weight of which urine metabolites had an independent predictive power of 12 % adjusting for all other lifestyle/clinical factors. First trimester metabolic phenotypes could not predict reproducibly weight at later stages of development. Physical activity, as well as other modifiable lifestyle/clinical factors, such as coffee consumption, vitamin D intake, and smoking, were identified as potential sources of metabolic variation during pregnancy. CONCLUSIONS: Significant reproducible maternal urinary metabolic signatures of fetal growth and birth weight are identified for the first time and linked to modifiable lifestyle factors. This novel approach to prenatal screening, combining multiple risk factors, present a great opportunity to personalize pregnancy management and reduce newborn disease risk in later life.

Drinking Water Disinfection By-products, Genetic Polymorphisms, and Birth Outcomes in a European Mother-Child Cohort Study.

BACKGROUND: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. METHODS: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies. RESULTS: Average levels of trihalomethanes ranged from around 10 µg/L to above the regulatory limits in the EU of 100 µg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (ß = 2.2 g in birth weight per 10 µg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 µg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. CONCLUSIONS: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. (See video abstract at http://links.lww.com/EDE/B104.).

Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London.

AIMS: Road traffic noise has been associated with hypertension but evidence for the long-term effects on hospital admissions and mortality is limited. We examined the effects of long-term exposure to road traffic noise on hospital admissions and mortality in the general population. METHODS AND RESULTS: The study population consisted of 8.6 million inhabitants of London, one of Europe's largest cities. We assessed small-area-level associations of day- (7:00-22:59) and nighttime (23:00-06:59) road traffic noise with cardiovascular hospital admissions and all-cause and cardiovascular mortality in all adults (≥25 years) and elderly (≥75 years) through Poisson regression models. We adjusted models for age, sex, area-level socioeconomic deprivation, ethnicity, smoking, air pollution, and neighbourhood spatial structure. Median daytime exposure to road traffic noise was 55.6 dB. Daytime road traffic noise increased the risk of hospital admission for stroke with relative risk (RR) 1.05 [95% confidence interval (CI): 1.02-1.09] in adults, and 1.09 (95% CI: 1.04-1.14) in the elderly in areas >60 vs. <55 dB. Nighttime noise was associated with stroke admissions only among the elderly. Daytime noise was significantly associated with all-cause mortality in adults [RR 1.04 (95% CI: 1.00-1.07) in areas >60 vs. <55 dB]. Positive but non-significant associations were seen with mortality for cardiovascular and ischaemic heart disease, and stroke. Results were similar for the elderly. CONCLUSIONS: Long-term exposure to road traffic noise was associated with small increased risks of all-cause mortality and cardiovascular mortality and morbidity in the general population, particularly for stroke in the elderly.