Longitudinal associations of DNA methylation and sleep in children : a meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.Peer reviewe

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Radiofequency electromagnetic fields exposure, sleep, and neurodevelopment in preadolescents and adolescents

The use of mobile communication devices (e.g. mobile phones, tablets, and laptops) increased during the last few years, especially in preadolescents and adolescents. In order to function, mobile communication devices require a constant exchange of information achieved using radiofrequency electromagnetic fields (RF-EMF). Evidence is limited for potential effects of RF-EMF exposure to the brain and epidemiological studies that assessed RF-EMF exposure and its relationship with sleep and neurodevelopment are scarce. This thesis aimed to better understand the potential association between RF-EMF exposure and sleep, and RF-EMF exposure and neurodevelopment by: i) using a comprehensive RF-EMF exposure assessment (i.e. distinguish between sources with different patterns of RF-EMF exposure to the brain such as phone calls, screen activities, and environmental sources, ii) estimating the amount of RF-EMF the brain absorbs from each source and overall, ii) assessing sleep using objective measures collected with actigraphy, and iii) assessing neurodevelopment as cognitive function and brain volumes. The use of some mobile communication devices such as the tablet and problematic mobile phone use were associated with poorer sleep quality and less favourable objective sleep measures. Moreover, evening whole-brain RF-EMF dose from phone calls was associated with less favourable objective sleep measures. Regarding neurodevelopment, overall whole-brain RF-EMF dose and whole-brain RF-EMF dose from phone calls were not associated with brain volumes but whole-brain RF-EMF dose from screen activities was associated with smaller caudate volume. Finally, overall whole-brain RF-EMF dose and whole-brain RF-EMF dose from phone calls was associated with non-verbal intelligence. Given that the biological mechanism behind the observed associations between RF-EMF exposure and sleep, and RF-EMF exposure and neurodevelopment is unknown, that we found small effects sizes, and that we could not entirely disentangle between minutes of use and RF-EMF dose, our results should be interpreted with caution. We cannot discard chance finding, reverse causality, or that other non-RF-EMF factors related to the use of mobile communication devices are behind the observed associations (e.g. blue light, addiction, mental arousal or sleep displacement).El uso de dispositivos móviles de comunicación como los teléfonos móviles, tabletas y ordenadores portátiles ha aumentado en los últimos años, especialmente en preadolescentes y adolescentes. Los dispositivos móviles de comunicación utilizan los campos electromagnéticos de radiofrecuencia (CEM-RF) para el intercambio constante de información necesario para su funcionamiento. La evidencia científica de los efectos que tiene la exposición a CEM-RF al cerebro es limitada y los estudios epidemiológicos que evalúan la exposición de CEM-RF y su relación con el sueño y el neurodesarrollo son escasos. Esta tesis tiene como objetivo entender mejor las asociaciones entre la exposición a CEM-RF y el sueño y la exposición a CEM-RF y el neurodesarrollo: i) haciendo una evaluación completa de la exposición de CEM-RF al cerebro, es decir, distinguiendo entre fuentes de CEM-RF con diferentes patrones de exposición al cerebro como las llamadas telefónicas, el uso de aparatos móviles de comunicación para actividades con pantalla y las fuentes ambientales, ii) estimando la cantidad de CEM- RF que el cerebro absorbe de cada fuente y en total, iii) evaluando el sueño utilizando medidas objetivas recogidas con actigrafia y iv) evaluando el neurodesarrollo como función cognitiva y volúmenes cerebrales. El uso de algunos dispositivos móviles de comunicación como por ejemplo la tableta y el uso problemático del teléfono móvil están associados con peor calidad y medidas objetivas del sueño. Además, hemos observado una asociación entre la dosis de CEM-RF al cerebro proveniente de las llamadas telefónicas por la tarde y peores medidas objetivas del sueño. En cuanto al neurodesarrollo, la dosis total de CEM-RF al cerebro y la dosis de CEM-RF al cerebro proveniente de las llamadas telefónicas no están asociadas con los volúmenes cerebrales, en cambio, la dosis de CEM-RF al cerebro proveniente de usos de aparatos móviles de comunicación para actividades con pantalla está asociada con un volumen más pequeño del núcleo caudado. Finalmente, la dosis total de CEM-RF al cerebro y la dosis de CEM-RF al cerebro proveniente de las llamadas telefónicas están asociadas con peor inteligencia no verbal. Teniendo en cuenta que se desconoce el mecanismo biológico que hay detrás de las asociaciones observadas entre la exposición a CEM-RF y el sueño y la exposición a CEM-RF y el neurodesarrollo, que los efectos que hemos encontrado son pequeños y que no hemos podido separar completamente entre los minutos de uso y la dosis de CEM-RF, nuestros resultados deben interpretarse con precaución. No podemos descartar hallazgo casual, causalidad inversa o que otros factores relacionados con el uso de dispositivos móviles de comunicación estén detrás de las asociaciones observadas. Por ejemplo, exposición a la luz azul, adicción a los dispositivos móviles de comunicación, excitación mental o desplazamiento del sueño.L’ús de dispositius mòbils de comunicació com els telèfons mòbils, tauletes i ordinadors portàtils ha augmentat els darrers anys, especialment en preadolescents i adolescents. Els dispositius mòbils de comunicació utilitzen els camps electromagnètics de radiofreqüència (CEM-RF) per l’intercanvi constant d’informació necessari pel seu funcionament. L’evidència científica dels efectes que té l’exposició de CEM-RF al cervell és limitada i els estudis epidemiològics que avaluaven l’exposició de CEM-RF i la seva relació amb el son i el neurodesenvolupament són escassos. Aquesta tesi té com a objectiu entendre millor les associacions entre l’exposició a CEM-RF i el son i l’exposició a CEM-RF i el neurodesenvolupament. Per fer-ho: i) hem fet una avaluació completa de l’exposició de CEM-RF al cervell, és a dir, distingint entre fonts de CEM-RF amb diferents patrons d’exposició al cervell com les trucades telefòniques, l’ús d’aparells mòbils de comunicació per activitats amb pantalla i les fonts ambientals, ii) hem estimat la quantitat de CEM-RF que el cervell absorbeix de cada font i en total, iii) hem avaluat el son utilitzant mesures objectives recollides amb actigrafia i iv) hem avaluat el neurodesenvolupament com a funció cognitiva i volums cerebrals. L’ús d’alguns dispositius mòbils de comunicació com per exemple la tauleta i l’ús problemàtic del telèfon mòbil estan associats amb pitjor qualitat i mesures objectives del son. A més a més, hem trobat una associació entre la dosi de CEM-RF al cervell provinent de les trucades telefòniques al vespre i pitjors mesures objectives del son. En relació amb el neurodesenvolupament, la dosi total de CEM-RF al cervell i la dosi de CEM-RF al cervell provinent de les trucades telefòniques no estan associades amb els volums cerebrals, en canvi, la dosi de CEM-RF al cervell provinent d’usos d’aparells mòbils de comunicaió per activitats amb pantalla està associada amb un volum més petit del nucli caudat. Finalment, la dosi total de CEM-RF al cervell i la dosi de CEM-RF al cervell provinent de les trucades telefòniques estan associades amb pitjor la intel·ligència no verbal. Tenint en compte que es desconeix el mecanisme biològic que hi ha darrere de les associacions observades entre l'exposició a CEM-RF i el son i l'exposició a CEM-RF i el neurodesenvolupament, que els efectes que hem trobat són petits i que no hem pogut separar completament entre els minuts d'ús dels dispositius mòbils de comunicació i la dosi de CEM-RF al cervell, els nostres resultats s’han d’interpretar amb precaució. No podem descartar que les troballes siguin casuals, causalitat inversa o que altres factors relacionats amb l’ús de dispositius mòbils de comunicació estiguin darrere de les associacions observades. Per exemple, exposició a la llum blava, addicció als aparells mòbils de comunicació, excitació mental o desplaçament del son

Telecommunication devices use, screen time and sleep in adolescents

Purpose: To investigate the association between telecommunication and other screen devices use and subjective and objective sleep measures in adolescents at 17–18 years. Methods: Cross-sectional study on adolescents aged 17–18 years from a Spanish population-based birth cohort established in Menorca in 1997–1998. Information on devices use was collected using self-reported questionnaires. Mobile Phone Problematic Use Scale was used to assess mobile phone use dependency. Pittsburgh Sleep Quality Index was used to assess subjective sleep (n = 226). ActiGraph wGT3X-BT for 7 nights was used to assess objective sleep (n = 110). Results: One or more cordless phone calls/week was associated with a lower sleep quality [Prevalence Ratio (PR) 1.30 (95%Confidence Interval (CI) 1.04; 1.62)]. Habitual and frequent problematic mobile phone use was associated with a lower sleep quality [PR 1.55 (95%CI 1.03; 2.33) and PR 1.67 (95%CI 1.09; 2.56), respectively]. Higher tablet use was associated with decreased sleep efficiency and increased minutes of wake time after sleep onset [β-1.15 (95%CI −1.99; −0.31) and β 7.00 (95%CI 2.40; 11.60) per increase of 10 min/day of use, respectively]. No associations were found between other devices and sleep measures. Conclusions: Frequency of cordless phone calls, mobile phone dependency, and tablet use were related to an increase of subjective and objective sleep problems in adolescents. These results seem to indicate that sleep displacement, mental arousal, and exposure to blue light screen emission might play a more important role on sleep than a high RF-EMF exposure to the brain. However, more studies are needed assessing personal RF-EMF levels to draw conclusions

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Background: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4-13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10-8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10-8, n = 577) and sleep onset latency (p = 8.8 × 10-9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716-2539). Conclusion: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available

Estimated all-day and evening whole-brain radiofrequency electromagnetic fields doses, and sleep in preadolescents

OBJECTIVE: To investigate the association of estimated all-day and evening whole-brain radiofrequency electromagnetic field (RF-EMF) doses with sleep disturbances and objective sleep measures in preadolescents. METHODS: We included preadolescents aged 9-12 years from two population-based birth cohorts, the Dutch Generation R Study (n = 974) and the Spanish INfancia y Medio Ambiente Project (n = 868). All-day and evening overall whole-brain RF-EMF doses (mJ/kg/day) were estimated for several RF-EMF sources including mobile and Digital Enhanced Cordless Telecommunications (DECT) phone calls (named phone calls), other mobile phone uses, tablet use, laptop use (named screen activities), and far-field sources. We also estimated all-day and evening whole-brain RF-EMF doses in these three groups separately (i.e. phone calls, screen activities, and far-field). The Sleep Disturbance Scale for Children was completed by mothers to assess sleep disturbances. Wrist accelerometers together with sleep diaries were used to measure sleep characteristics objectively for 7 consecutive days. RESULTS: All-day whole-brain RF-EMF doses were not associated with self-reported sleep disturbances and objective sleep measures. Regarding evening doses, preadolescents with high evening whole-brain RF-EMF dose from phone calls had a shorter total sleep time compared to preadolescents with zero evening whole-brain RF-EMF dose from phone calls [-11.9 min (95%CI -21.2; -2.5)]. CONCLUSIONS: Our findings suggest the evening as a potentially relevant window of RF-EMF exposure for sleep. However, we cannot exclude that observed associations are due to the activities or reasons motivating the phone calls rather than the RF-EMF exposure itself or due to chance finding

Estimated all-day and evening whole-brain radiofrequency electromagnetic fields doses, and sleep in preadolescents

OBJECTIVE: To investigate the association of estimated all-day and evening whole-brain radiofrequency electromagnetic field (RF-EMF) doses with sleep disturbances and objective sleep measures in preadolescents. METHODS: We included preadolescents aged 9-12 years from two population-based birth cohorts, the Dutch Generation R Study (n = 974) and the Spanish INfancia y Medio Ambiente Project (n = 868). All-day and evening overall whole-brain RF-EMF doses (mJ/kg/day) were estimated for several RF-EMF sources including mobile and Digital Enhanced Cordless Telecommunications (DECT) phone calls (named phone calls), other mobile phone uses, tablet use, laptop use (named screen activities), and far-field sources. We also estimated all-day and evening whole-brain RF-EMF doses in these three groups separately (i.e. phone calls, screen activities, and far-field). The Sleep Disturbance Scale for Children was completed by mothers to assess sleep disturbances. Wrist accelerometers together with sleep diaries were used to measure sleep characteristics objectively for 7 consecutive days. RESULTS: All-day whole-brain RF-EMF doses were not associated with self-reported sleep disturbances and objective sleep measures. Regarding evening doses, preadolescents with high evening whole-brain RF-EMF dose from phone calls had a shorter total sleep time compared to preadolescents with zero evening whole-brain RF-EMF dose from phone calls [-11.9 min (95%CI -21.2; -2.5)]. CONCLUSIONS: Our findings suggest the evening as a potentially relevant window of RF-EMF exposure for sleep. However, we cannot exclude that observed associations are due to the activities or reasons motivating the phone calls rather than the RF-EMF exposure itself or due to chance finding

Estimated whole-brain and lobe-specific radiofrequency electromagnetic fields doses and brain volumes in preadolescents

OBJECTIVE: To assess the association between estimated whole-brain and lobe-specific radiofrequency electromagnetic fields (RF-EMF) doses, using an improved integrated RF-EMF exposure model, and brain volumes in preadolescents at 9-12 years old. METHODS: Cross-sectional analysis in preadolescents aged 9-12 years from the Generation R Study, a population-based birth cohort set up in Rotterdam, The Netherlands (n = 2592). An integrated exposure model was used to estimate whole-brain and lobe-specific RF-EMF doses (mJ/kg/day) from different RF-EMF sources including mobile and Digital Enhanced Cordless Telecommunications (DECT) phone calls, other mobile phone uses than calling, tablet use, laptop use, and far-field sources. Whole-brain and lobe-specific RF-EMF doses were estimated for all RF-EMF sources together (i.e. overall) and for three groups of RF-EMF sources that lead to a different pattern of RF-EMF exposure. Information on brain volumes was extracted from magnetic resonance imaging scans. RESULTS: Estimated overall whole-brain RF-EMF dose was 84.3 mJ/kg/day. The highest overall lobe-specific dose was estimated in the temporal lobe (307.1 mJ/kg/day). Whole-brain and lobe-specific RF-EMF doses from all RF-EMF sources together, from mobile and DECT phone calls, and from far-field sources were not associated with global, cortical, or subcortical brain volumes. However, a higher whole-brain RF-EMF dose from mobile phone use for internet browsing, e-mailing, and text messaging, tablet use, and laptop use while wirelessly connected to the internet was associated with a smaller caudate volume. CONCLUSIONS: Our results suggest that estimated whole-brain and lobe-specific RF-EMF doses were not related to brain volumes in preadolescents at 9-12 years old. Screen activities with mobile communication devices while wirelessly connected to the internet lead to low RF-EMF dose to the brain and our observed association may thus rather reflect effects of social or individual factors related to these specific uses of mobile communication devices. However, we cannot discard residual confounding, chance finding, or reverse causality. Further studies on mobile communication devices and their potential negative associations with brain development are warranted, regardless whether associations are due to RF-EMF exposure or to other factors related to their use

Association between estimated whole-brain radiofrequency electromagnetic fields dose and cognitive function in preadolescents and adolescents

Objective: To investigate the association between estimated whole-brain radiofrequency electromagnetic fields (RF-EMF) dose, using an improved integrated RF-EMF exposure model, and cognitive function in preadolescents and adolescents. Methods: Cross-sectional analysis in preadolescents aged 9–11 years and adolescents aged 17–18 years from the Dutch Amsterdam Born Children and their Development Study (n = 1664 preadolescents) and the Spanish INfancia y Medio Ambiente Project (n = 1288 preadolescents and n = 261 adolescents), two population-based birth cohort studies. Overall whole-brain RF-EMF doses (mJ/kg/day) were estimated for several RF-EMF sources together including mobile and Digital Enhanced Cordless Telecommunications phone calls (named phone calls), other mobile phone uses than calling, tablet use, laptop use (named screen activities), and far-field sources. We also estimated whole-brain RF-EMF doses in these three groups separately (i.e. phone calls, screen activities, and far-field) that lead to different patterns of RF-EMF exposure. We assessed non-verbal intelligence in the Dutch and Spanish preadolescents, information processing speed, attentional function, and cognitive flexibility in the Spanish preadolescents, and working memory and semantic fluency in the Spanish preadolescents and adolescents using validated neurocognitive tests. Results: Estimated overall whole-brain RF-EMF dose was 90.1 mJ/kg/day (interquartile range (IQR) 42.7; 164.0) in the Dutch and Spanish preadolescents and 105.1 mJ/kg/day (IQR 51.0; 295.7) in the Spanish adolescents. Higher overall estimated whole-brain RF-EMF doses from all RF-EMF sources together and from phone calls were associated with lower non-verbal intelligence score in the Dutch and Spanish preadolescents (−0.10 points, 95% CI -0.19; −0.02 per 100 mJ/kg/day increase in each exposure). However, none of the whole-brain RF-EMF doses was related to any other cognitive function outcome in the Spanish preadolescents or adolescents. Conclusions: Our results suggest that higher brain exposure to RF-EMF is related to lower non-verbal intelligence but not to other cognitive function outcomes. Given the cross-sectional nature of the study, the small effect sizes, and the unknown biological mechanisms, we cannot discard that our resultsare due to chance finding or reverse causality. Longitudinal studies on RF-EMF brain exposure and cognitive function are needed

Estimated whole-brain and lobe-specific radiofrequency electromagnetic fields doses and brain volumes in preadolescents

Objective: To assess the association between estimated whole-brain and lobe-specific radiofrequency electromagnetic fields (RF-EMF) doses, using an improved integrated RF-EMF exposure model, and brain volumes in preadolescents at 9-12 years old. Methods: Cross-sectional analysis in preadolescents aged 9-12 years from the Generation R Study, a population-based birth cohort set up in Rotterdam, The Netherlands (n = 2592). An integrated exposure model was used to estimate whole-brain and lobe-specific RF-EMF doses (mJ/kg/day) from different RF-EMF sources including mobile and Digital Enhanced Cordless Telecommunications (DECT) phone calls, other mobile phone uses than calling, tablet use, laptop use, and far-field sources. Whole-brain and lobe-specific RF-EMF doses were estimated for all RF-EMF sources together (i.e. overall) and for three groups of RF-EMF sources that lead to a different pattern of RF-EMF exposure. Information on brain volumes was extracted from magnetic resonance imaging scans. Results: Estimated overall whole-brain RF-EMF dose was 84.3 mJ/kg/day. The highest overall lobe-specific dose was estimated in the temporal lobe (307.1 mJ/kg/day). Whole-brain and lobe-specific RF-EMF doses from all RF-EMF sources together, from mobile and DECT phone calls, and from far-field sources were not associated with global, cortical, or subcortical brain volumes. However, a higher whole-brain RF-EMF dose from mobile phone use for internet browsing, e-mailing, and text messaging, tablet use, and laptop use while wirelessly connected to the internet was associated with a smaller caudate volume. Conclusions: Our results suggest that estimated whole-brain and lobe-specific RF-EMF doses were not related to brain volumes in preadolescents at 9-12 years old. Screen activities with mobile communication devices while wirelessly connected to the internet lead to low RF-EMF dose to the brain and our observed association may thus rather reflect effects of social or individual factors related to these specific uses of mobile communication devices. However, we cannot discard residual confounding, chance finding, or reverse causality. Further studies on mobile communication devices and their potential negative associations with brain development are warranted, regardless whether associations are due to RF-EMF exposure or to other factors related to their use