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Multi-omics signatures of the human early life exposome
Maitre L, Bustamante M, Hernández-Ferrer C, Thiel D, Lau CE, Siskos AP, Vives-Usano M, Ruiz-Arenas C, Pelegrí-Sisó D, Robinson O, Mason D, Wright J, Cadiou S, Slama R, Heude B, Casas M, Sunyer J, Papadopoulou EZ, Gutzkow KB, Andrusaityte S, Grazuleviciene R, Vafeiadi M, Chatzi L, Sakhi AK, Thomsen C, Tamayo I, Nieuwenhuijsen M, Urquiza J, Borràs E, Sabidó E, Quintela I, Carracedo Á, Estivill X, Coen M, González JR, Keun HC, Vrijheid M. Multi-omics signatures of the human early life exposome. Nat Commun. 2022 Nov 21;13(1):7024. PMID: 36411288
Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data
D’Cruz SC, Hao C, Labussiere M, Mustieles V, Freire C, Legoff L, Magnaghi-Jaulin L, Olivas-Martinez A, Rodriguez-Carrillo A, Jaulin C, David A, Fernandez MF, Smagulova F. Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data. Clin Epigenetics. 2022 Dec 26;14(1):186. PMID: 36572933
Validation of a Parent-Reported Physical Activity Questionnaire by Accelerometry in European Children Aged from 6 to 12 Years Old
Prieto-Botella D, Valera-Gran D, Santa-Marina L, Babarro I, Subiza-Pérez M, Casas M, Guxens M, Cárdenas-Fuentes G, Heude B, Bernard JY, McEachan RRC, García-Aymerich J, Vrijheid M, Navarrete-Muñoz EM. Validation of a Parent-Reported Physical Activity Questionnaire by Accelerometry in European Children Aged from 6 to 12 Years Old. Int J Environ Res Public Health. 2022 Jul 27;19(15):9178. PMID: 35954544
Prenatal exposure to mixtures of phthalates and phenols and body mass index and blood pressure in Spanish preadolescents
Güil-Oumrait N, Cano-Sancho G, Montazeri P, Stratakis N, Warembourg C, Lopez-Espinosa MJ, Vioque J, Santa-Marina L, Jimeno-Romero A, Ventura R, Monfort N, Vrijheid M, Casas M. Prenatal exposure to mixtures of phthalates and phenols and body mass index and blood pressure in Spanish preadolescents. Environ Int. 2022 Nov;169:107527. PMID: 36126421
INMA: “Exposure to persistent organic pollutants during pregnancy may affect cardiometabolic health in preadolescents”
Prevalence of childhood obesity has been increasing in the past decade, and today 33% of the European children are considered overweight or obese. Childhood obesity is a major public health concern, since it has been linked to higher risk of adult obesity and poorer cardiometabolic health in later life. Some persistent organic pollutants (POPs) are suspected to alter hormonal metabolisms and may affect human cardiometabolic health. POPs include organochlorine pesticides (e.g., p,p’-DDT, HCB, β-HCH), as well as industrial chemical (PCB). The production and use of these chemicals have been banned under the Stockholm Convention decades ago. However, due to their high persistence in the environment, they are still detected in human bodies, including pregnant women and children. Populations are mostly exposed by contaminated food. During pregnancy, maternal levels of POPs are transmitted to the child through the placenta, and postnatally, via breast milk. In previous studies, prenatal exposure to POPs has been associated with a risk of elevated body mass index (BMI) and elevated blood pression in childhood. Nevertheless, few studies have investigated whether these associations persist into preadolescence. Also, previous literature has mostly assessed single POPs exposures and did not consider POPs exposure as a mixture. The main objective of the study was to determine whether prenatal exposure to POPs could affect cardiometabolic health in preadolescents, using adiposity markers and blood pressure data from two birth cohorts in Europe. A total of 1667 children from the INMA-Gipuzkoa, -Sabadell, -Valencia study (Spain) and the PELAGIE cohort (France) were included. POPs levels were assessed in maternal serum collected at 12 weeks of gestation and in umbilical cord serum, for the INMA study and the PELAGIE cohort, respectively. When children reached 11-13 years, clinical examinations were carried out to measure BMI, percentage of fat mass, abdominal obesity, overweight/obese status, and systolic and diastolic blood pressure. The results suggest that higher prenatal exposure to POPs mixture was associated with higher BMI and body fat, and higher risk of being overweight/obese at preadolescence, with no evidence of sex difference. HCB was the main contributor to these effects, followed by β-HCH and p,p’-DDE. β-HCH and p,p’-DDE were also associated with higher systolic blood pressure, especially in girls. Charline Warembourg, last author of the study, say that “these findings confirm that prenatal exposure to organochlorine pesticides is associated with an increased risk of obesity, until adolescence.” She adds that “it is necessary to study whether or not these effects persist in later life”. Reference: Rouxel E, Costet N, Monfort C, Audouze K, Cirugeda L, Gaudreau E, Grimalt JO, Ibarluzea J, Lainé F, Llop S, Lopez-Espinosa MJ, Rouget F, Santa-Marina L, Vrijheid M, Chevrier C, Casas M, Warembourg C. Prenatal exposure to multiple persistent organic pollutants in association with adiposity markers and blood pressure in preadolescents. Environ Int. 2023 Jun 22;178:108056. doi: 10.1016/j.envint.2023.108056. Epub ahead of print. PMID: 37379720. Link to scientific article: https://doi.org/10.1016/j.envint.2023.108056
Urban environment and combinations of health-related behaviors in young children
New project in progress: Description Location: Barcelona/Paris Data protection The processing of your data responds to a mission of public interest vested in Inserm, which justifies the processing of your personal health data for scientific research purposes. Your personal data will be processed in a manner that ensures appropriate respect of the original INMA project research objectives. The aim of this project, based on data from different mother-child cohorts (INMA, Spain; EDEN, France, and BiB, United Kingdom), is to study the links between urban environment variables early in life and a combination of sub-optimal behaviors identified at pre-school age (3-4 years). The data used in this project (socio-economic, socio-demographic and financial information, lifestyle, biometric data, environment variables) will be kept in an active database for one year (until the end of February 2024). Your participation is optional and you have: You may exercise your rights by sending a request to the Data Protection Officer via email (lopd@isglobal.org) or the ISGlobal postal address: c/ Rosselló, 132, 08036 Barcelona, Spain. If you encounter any difficulty in exercising your rights, you may file a claim with the Spanish Data Protection Agency at any time (www.aepd.es – C/ Jorge Juan, 6, Madrid). Please refer to the following section in order to read more about how to exercise your rights : https://www.proyectoinma.org/en/privacy-policy/
“Urban environment and combinations of health-related behaviors in young children”
Efforts to modify diet, screen time, physical activity and sleep without considering the context of children’s lives have met with limited success in improving their health. This is because the environment influences the emergence of these behaviors and their maintenance as habits. By adopting a global perspective, the “Urban environment and combinations of health-related behaviors in young children” project proposes to study how the urban environment (i.e. green spaces, road traffic, the built environment and pollution) contributes to shaping sub-optimal combinations of health-related behaviors in INMA Project children, as well as those of children participating in two other European cohorts (EDEN – France; BiB – UK). The focus is on pre-school age, a key window of opportunity for prevention and adoption of health-promoting behaviors.
Funding: Réseau Doctoral en Santé Publique led by the Ecole des Hautes Etudes en Santé Publique
Project started on 01/02/2023
The data processing required to implement this project is placed under the responsibility of Inserm, the research promoter (Article 6, GDPR). The data processor is DESCARPENTRIE Alexandra.
– the right to access your personal data, in order to check its accuracy and, if necessary, to rectify, complete or update it.
– the right to object at any time to the transmission of your data. If you exercise this right, your participation in this study will immediately cease.
– the right to restrict data processing: no further operations may be carried out on your data for a period enabling the controller/processor to verify the accuracy of the personal data.
– the right to erasure: i.e. to withdraw consent on which the processing is based at any time, without having to justify your decision.
INMA:”Bullying from a biopsychosocial perspective: A study of the INMA project integrates hormonal markers to the study of bullying”
A study conducted as part of the INMA cohort studied bullying from a biopsychosocial perspective, integrating biological variables such as hormone levels into bullying behavior. Bullying is defined as a type of aggressive behavior that occurs in the school context and typically occurs during childhood and adolescence. Despite sharing the intentionality that also appears in aggressiveness, bullying presents two other characteristics that make it a unique behavior. These include the repetitiveness of the actions and the imbalance of power between the victim and the bully. Bullying is currently considered a public health problem that affects about one third of students worldwide. Being involved in bullying situations during childhood and adolescence can have serious consequences in different spheres of a person’s life, both short and long term. It is thus imperative to study the factors associated with bullying behavior to try to understand this phenomenon in its totality. The most recent research indicates that the origin of aggressive behavior is multi-causal and that it is influenced by biological, social, and cultural factors. Although human behavior in general has been studied from a psychosocial point of view, more and a growing body of research is attempting to focus on the study of biological factors. However, few studies have tried to explore the possible biological markers of bullying. Regarding biological factors that influence behavior, previous research has focused on the role of hormones, specifically testosterone and cortisol, at two developmental periods. The prenatal and pubertal periods are two developmental stages sensitive to the effects that hormones have on the nervous system and therefore on behaviors dependent on brain structures altered by these hormones. Based on all this, a study of the INMA project decided to explore bullying behavior from a biopsychosocial perspective, taking into account the effects that could have both social psychological variables and hormonal levels of preadolescents. The study was carried out with 302 preadolescents from the INMA project cohort in Gipuzkoa. When the preadolescents were 11 years old, information about bullying behavior was collected using a questionnaire. In addition, information on several psychological and social variables (executive function, family context, school context and social context) was collected by asking these pre-adolescents and their relatives. Data on prenatal and prepubertal hormone levels were determined by saliva samples and the 2D:4D ratio. The results showed that 9.6% of the participants were involved as victims, 1.7% as bullies and another 1.7% as bullies/victims. The study found that only the bullying role in boys appeared to be influenced by both hormonal levels and psychosocial variables. Specifically, it was observed that lower prepubertal cortisol levels together with a poorer perception of the school environment and lower peer and social group support were associated with a higher risk of being involved in bullying situations as bullies. The findings of this study are in line with what previous researchers have found in other studies. However, there is still limited evidence on the role of biological factors in bullying. Therefore, the study of bullying should continue to be approached from a biopsychosocial perspective. Identifying the hormonal levels that may affect this behavior, as well as the variables of interest from a more psychosocial aspect, we will be able to better profile those people who are vulnerable to being involved in this type of situation and also to develop bullying prevention and intervention programs in order to reduce its prevalence or the percentage of participants involved. Reference: Babarro I, Andiarena A, Fano E, García-Baquero G, Lebeña A, Arranz-Freijo EB, Ibarluzea J. Do prepubertal hormones, 2D:4D index and psychosocial context jointly explain 11-year-old preadolescents’ involvement in bullying? Biol Psychol. 2022 Jul;172:108379. doi: 10.1016/j.biopsycho.2022.108379. Epub 2022 Jun 8. Link to scientific article: https://www.sciencedirect.com/science/article/pii/S0301051122001223?via%3Dihub
INMA: “INMA Study Investigates Link Between Pesticide Exposure and Puberty Development in Children”
A recent study conducted as part of the INMA cohort has delved into the potential link between pesticide exposure and the development of puberty in children. Pesticides are chemical substances or mixtures designed to control, prevent, repel, or destroy pests that can adversely impact agricultural productivity. These pests can range from insects and weeds to fungi, rodents, and disease-causing pathogens. Pesticides come in various forms such as sprays, powders, liquids, granules, or baits and are applied to crops, soil, water, or structures. Although the use of pesticides offers benefits, including protecting crops, improving agricultural yields, and preventing the spread of diseases carried by pests, their improper use or over-reliance can have adverse effects on human health. Pesticides are primarily consumed through conventionally grown fruits and vegetables, making diet the main exposure route for the general population. These chemicals have raised concerns due to their potential to disrupt the normal functioning of hormones in the human body, and are widely classified as endocrine-disrupting chemicals (EDCs). Experimental evidence suggests that these EDCs may have adverse effects on puberty timing in children. The timing of puberty, in turn, can have various health implications for individuals – it might affect personal and emotional well-being, growth and bone health, reproductive health, and associate with other health risks in the future, such as obesity, type 2 diabetes, cardiovascular risk, or even breast cancer. However, existing studies present conflicting findings on the relationship between pesticide exposure and puberty. Some studies indicate that certain pesticides are associated with early puberty in girls, while others report delayed sexual development in both boys and girls. These effects have been observed across various countries, including the UK, Belgium, China, and Denmark. Given Spain’s significant consumption of pesticides within the European Union, the researchers aimed to investigate the potential association between exposure to pesticides and puberty development in children from the INMA cohort. The study examined the levels of pesticide metabolites in urine samples collected from children aged 7 to 11 years and assessed their pubertal development using Tanner stages and the Pubertal Development Scale. Pesticide metabolites measured were: a metabolite of chlorpyrifos; a metabolite of diazinon; a non-specific metabolite of organophosphates; a metabolite of pyrethroids; and a metabolite of fungicides. These pesticides are of great interest because they are commonly used in food production and non-agricultural settings. The findings revealed that higher concentrations of specific pesticide metabolites, such as the metabolites of organophosphates and of fungicides, were associated with an increased likelihood of overall puberty development in girls. The metabolite of fungicides was also linked to a higher probability of breast development, particularly in girls with underweight or normal weight. In boys, the urinary presence of the metabolites of chlorpyrifos and of pyrethroids was associated with a greater likelihood of genital development. Interestingly, the association for the pyrethroids metabolite was observed primarily in boys with overweight or obesity. Furthermore, the study found that higher urinary concentrations of the metabolite of fungicides were associated with an increased likelihood of genital development in boys who had underweight or normal weight. On the other hand, higher levels of organophosphates were linked to reduced odds of puberty in boys with overweight or obesity Overall, this INMA study suggests that exposure to certain pesticides during childhood may be associated to pubertal outcomes, including earlier breast development in girls and earlier genital development in boys. Interestingly, these associations might be affected by childhood obesity status. The study highlights the potential interference of these contemporary pesticides with the hypothalamic-pituitary-gonadal (HPG) axis, which regulates pubertal timing. These findings shed light on the potential health impacts of pesticide exposure during critical stages of development and emphasize the need for further investigation into the effects of these chemicals on pubertal development. Reference: Castiello F, Suárez B, Beneito A, Lopez-Espinosa MJ, Santa-Marina L, Lertxundi A, Tardón A, Riaño-Galán I, Casas M, Vrijheid M, Olea N, Fernández MF, Freire C. Childhood exposure to non-persistent pesticides and pubertal development in Spanish girls and boys: Evidence from the INMA (Environment and Childhood) cohort. Environ Pollut. 2023 Jan 1;316(Pt 2):120571. Link to scientific article: https://doi.org/10.1016/j.envpol.2022.120571
INMA: “Do sedentary behaviours affect the length of telomeres in childhood?”
Our colleague Daniel Prieto has recently published the following scientific article with information from the INMA Study: (https://www.mdpi.com/1660-4601/20/6/5134) in which the relationship between sedentary behaviours and the length of the telomeres is explored. But what are telomeres? Telomeres are structures found at the ends of chromosomes, which are made up of DNA and protein sequences. These telomeres act as “plugs” which protect the genetic material of the chromosomes and prevent them from deteriorating. As our cells divide, telomeres naturally shorten, contributing to the aging process. The innovation of this work is to verify the effect of sedentary behaviours on the length of telomeres. Sedentary behaviours, downtime in front of the television, video games, etc., during childhood can have negative effects on the health and well-being of children. In particular, there are studies that have shown that more time dedicated to sedentary behaviours in childhood influences having less muscular development, less concentration and poorer academic performance, as well as affecting their interaction and socialization skills. In addition, scientific evidence has observed that more time dedicated to sedentary behaviours in childhood can influence having more obesity, cardiovascular problems, type 2 diabetes, and anxiety and depression in adult life. Regarding telomeres, sedentary behaviours could contribute to accelerate their shortening due to their oxidative and inflammatory action on the cells of our body. However, to date no studies have been carried out to see if sedentary behaviours influence telomere length in childhood. Thanks to the participation of 669 children from the INMA Study who gave a blood sample and answered several questionnaires at 4 years of age and 530 children at 8 years of age, this manuscript has been possible. These blood samples allowed us to determine telomere length at 4 and 8 years and with these measurements we were able to calculate changes between 4-8 years. In addition, at the follow-up visit at child’s age 4, information was collected on the sedentary behaviours reported by the parents. Specifically, screen viewing time (television, videos, etc.), other sedentary activities (puzzles, reading, homework, etc.) and total time (the sum of these two) were calculated. These variables were transformed into three levels of sedentary behaviours (low, medium or high level). The results obtained showed that children who spent more time viewing screens at age 4 (highest level, between 1.6 and 5.0 hours a day) had a telomere length 3.9% shorter compared to children at the lowest level (between 0 and 1.0 hours per day). In addition, these children exposed to more screen time at age 4 showed a greater acceleration of telomere shortening. This study corroborates the potential negative effect of sedentary behaviours during childhood with respect to cellular longevity and focuses on the importance of promoting an active lifestyle from an early age to promote the health of children. If you want to know more about telomeres, you can consult the following informative video: https://www.youtube.com/watch?v=IvnMDa-p-nE&t=46s&ab_channel=UniversidadMiguelHern%C3%A1ndezdeElche Reference: Prieto-Botella D, Martens DS, Valera-Gran D, Subiza-Pérez M, Tardón A, Lozano M, Casas M, Bustamante M, Jimeno-Romero A, Fernández-Somoano A, Llop S, Vrijheid M, Nawrot TS, Navarrete-Muñoz EM. Sedentary Behaviour and Telomere Length Shortening during Early Childhood: Evidence from the Multicentre Prospective INMA Cohort Study. Int J Environ Res Public Health. 2023 Mar 14;20(6):5134. Link to the scientific article: https://www.mdpi.com/1660-4601/20/6/5134
INMA: “Does environmental noise affect sleep in preadolescence?”
Exposure to environmental noise, especially road traffic noise, is an important and growing public health concern. More than 100 million European citizens are exposed to an average daily noise level from road traffic of at least 55 dB, whereas the World Health Organization (WHO) recommends reducing road-traffic noise levels to 53 dB. Sleep is an essential biological process that serves vital functions, including promotion of neuroplasticity and neural development. Sleep disruption has been related with numerous short- and long-term health consequences. Short-term consequences include increased stress responsivity, cognitive deficits as well as emotional and behavioral problems. Long-term consequences of sleep disruption include hypertension, cardiovascular diseases, and diabetes mellitus type 2. Several studies have linked environmental noise exposure to higher sleep disturbances in adults, but are less conclusive in children. To date, most studies have used parental- or self-reports to characterize sleep, and few studies have included objective measurements to assess sleep quality. Also, previous literature has mostly ignored other noise sources such as railway, aircraft, or industry, which could play a different role in sleep patterns. The main objective of the study was to determine whether road traffic and multiple noise exposure (i.e. road, railway, aircraft, and industry) could affect sleep in preadolescents, using maternal-reported and wrist-actigraphy data from two birth cohorts in Europe. A total of 1477 children aged 12 years from the INMA Sabadell (Spain) and the Generation R Study (the Netherlands) were included. Noise levels were modelled at the participants addresses using noise maps created in 2012. Children’s sleep disturbances were reported by mothers through questionnaires for assessing: i) problems with initiating and maintaining sleep, ii) excessive somnolence, and iii) arousal problems (i.e. partial awakening from deep to light sleep, or from sleep to a state of being awake in which the subjects are partially or totally unconscious). Sleep was objectively measured with a wrist accelerometer placed on the non-dominant wrist during 7 days for obtaining the following physiological parameters: total sleep time (i.e., total amount of time asleep during the night, extracting time scored as awake in between), sleep efficiency (i.e., ratio of total sleep time to total time in bed), sleep onset latency (i.e., time a child needs to fall asleep), and wake after sleep onset (i.e., amount of time a child spends awake, starting from the time they fall asleep until the time they become fully awake). Lifestyle and socioeconomic variables were recorded using questionnaires and instruments completed by the parents. Exposure to road traffic noise was on average 53.2 dB in the Generation R Study and 61.3 dB in the INMA-Sabadell cohort. Results suggest that exposure to noise was related with reduced total sleep time and longer wake after sleep onset in both cohorts. Authors reported no association between noise exposure and maternal-reported sleep disturbances. Results were similar for multiple noise exposure, but most of the association was attributable to road traffic noise as it is the most predominant noise source. Authors say that “although the observed estimates were relatively small, these results might be more meaningful at the population-level due to the high prevalence of exposure to environmental noise”. Referencia: Pérez-Crespo L, Essers E, Foraster M, Ambrós A, Tiemeier H, Guxens M. Outdoor residential noise exposure and sleep in preadolescents from two European birth cohorts. Environ Res. 2023 Feb 16;225:115502. doi: 10.1016/j.envres.2023.115502. Epub ahead of print Link al artículo científico: https://doi.org/10.1016/j.envres.2023.115502
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