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The adverse effects on the child of maternal smoking in pregnancy is well-recognized, but little research has been carried out on the possible non-genetic effects of ancestral smoking prior to the pregnancy including parental initiation of cigarette smoking in their own childhoods or a grandmother smoking during pregnancy. Here, we summarize the studies that have been published mainly using data from the Avon Longitudinal Study of Parents and Children. We demonstrate evidence that ancestral smoking prior to or during pregnancy can often be beneficial for offspring health and both ancestor- and sex-specific. More specifically, we report evidence of (i) adverse effects of the father starting to smoke pre-puberty on his son's development; (ii) beneficial effects on the grandson if his maternal grandmother had smoked in pregnancy; and (iii) mainly adverse effects on the granddaughter when the paternal grandmother had smoked in pregnancy. The ancestor- and sex-specificity of these results are consistent with earlier studies reporting associations of health and mortality with ancestral food supply in their parents' and grandparents' pre-pubertal childhoods.
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Coorte de Nascimento , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Inglaterra/epidemiologia , Feminino , Avós , Humanos , Estudos Longitudinais , Masculino , Pais , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores SexuaisRESUMO
BACKGROUND: The majority of epidemiological studies concerning possible adverse effects of paracetamol (acetaminophen) in pregnancy have been focussed on childhood asthma. Initial results of a robust association have been confirmed in several studies. Recently, a few cohort studies have looked at particular neurocognitive outcomes, and several have implicated hyperactivity. OBJECTIVES: In order to confirm these findings, further information and results are required. Here, we assess whether paracetamol intake between 18 and 32 weeks gestation is associated with childhood behavioural and cognitive outcomes using a large population. METHODS: Data collected by the Avon Longitudinal Study of Parents and Children (ALSPAC) at 32 weeks gestation and referring to the period from 18 to 32 weeks, identified 43.9% of women having taken paracetamol. We used an exposome analysis first to determine the background factors associated with pregnant women taking the drug, and then allowed for those factors to assess associations with child outcomes (measured using regression analyses). RESULTS: We identified 15 variables independently associated with taking paracetamol in this time period, which were used as potential confounders. Of the 135 neurocognitive variables considered, adjusting for the likelihood of false discovery, we identified 56 outcomes for adjusted analyses. Adjustment identified 12 showing independent associations with paracetamol use at P < .05, four of which were at P < .0001 (all related to child behaviours reported by the mother at 42 and 47 months; eg conduct problems: adjusted mean score + 0.22 (95% confidence interval 0.10, 0.33)). There were few associations with behavioural or neurocognitive outcomes after age 7-8 years, whether reported by the mother or the teacher. CONCLUSIONS: If paracetamol use in mid-to-late pregnancy has an adverse effect on child neurocognitive outcome, it appears to mainly relate to the pre-school period. It is important that these results be tested using other datasets or methodologies before assuming that they are causal.
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Acetaminofen , Transtornos do Comportamento Infantil , Comportamento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Temperamento/efeitos dos fármacos , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Fatores Etários , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/uso terapêutico , Criança , Transtornos do Comportamento Infantil/induzido quimicamente , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/epidemiologia , Pré-Escolar , Expossoma , Feminino , Idade Gestacional , Humanos , Lactente , Estudos Longitudinais , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores Sexuais , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To investigate whether parental external locus of control (ELOC) measured in pregnancy is related to obesity in their adolescent offspring and whether the child's own ELOC measured at age 8 contributes. To determine whether associations are due to types of behaviour used by externally oriented participants. SUBJECTS/METHODS: Longitudinal pre-birth cohort study (Avon Longitudinal Study of Parents & Children (ALSPAC)) set in south-west England. Families whose adolescent offspring had their fat mass measured using DXA scans at any of ages 9, 11, 13, 15 or 17 (range, n = 7329 at 9 to n = 4850 at 17). The primary outcome measures were mean fat mass, and obesity measured as ≥85th centile of fat mass at each age. RESULTS: We found that parent and child externality was associated with greater fat mass [e.g., mean difference at age 15 associated with maternal ELOC was 1.70 kg (+1.17, +2.24), paternal ELOC 1.49 kg (+0.89, +2.09) and child's ELOC 1.50 kg (+0.93, +2.06) (P < 0.0001)]. Further analyses showed that factors associated with parent behaviour such as smoking in pregnancy, failure to breast feed, and early introduction of solids accounted for a third of the excess fat mass associated with maternal externality, whereas aspects of diet and energetic activity in later childhood were not. Further analyses demonstrated that the child's own ELOC only became independently important for adolescent obesity from age 13, whereas the mothers' and to a lesser extent the fathers' ELOC were associated at each age. CONCLUSIONS: There is increased interest in determining factors that may be involved in the aetiology and maintenance of excessive weight in adolescents. We demonstrate that parental locus of control is a promising candidate. We suggest interventions to change parents' locus of control towards internality in pregnancy might have long-term preventative benefits on the likelihood of obesity in the offspring.
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Dieta/psicologia , Controle Interno-Externo , Poder Familiar/psicologia , Obesidade Infantil/psicologia , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Dieta/estatística & dados numéricos , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Fenômenos Fisiológicos da Nutrição , Obesidade Infantil/etiologia , Obesidade Infantil/fisiopatologia , Fatores de Tempo , Aumento de PesoRESUMO
Although locus of control (LOC) has been the focus of thousands of studies we know little about how or if it changes over time and what is associated with change. Our lack of knowledge stems in part from the past use of cross-sectional and not longitudinal methodologies to study small numbers of participants from non-representative populations. The purpose of the present study was to use a longitudinal design with a large representative population to provide relevant information concerning the stability and change of adult LOC. Before the birth of their child, and again six years later, mothers and their partners participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) completed LOC tests and structured stressful events surveys. Analyses revealed that stresses experienced in relationships with spouses, friends and family, financial stability and job security, and illness/smoking were associated with changes in LOC. Results suggest substantial variation of LOC within spousal/parent dyads and moderate stability of LOC over time for both men and women. Stressors associated with change in LOC may be possible candidates when considering interventions to modify LOC expectancies.
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The Avon Longitudinal Study of Parents and Children (ALSPAC) collected information from the enrolled pregnancy onwards to identify features of the environment in which the study child was brought up. Among data collected were features concerning the health of the mothers' partners - generally the study father. This was an important feature since the father's physical and mental health can have a long-term effect on the family. In this Data Note we describe the data available on the father's health from pregnancy until 12 years after the offspring was born. Not only is this a valuable addition to the environmental information available for studies of the child's development and the mental health of the mother over time, but it will provide a useful description of the father himself during adulthood.
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At the time of planning ALSPAC there was accumulating evidence that abuse and other childhood traumas were related to psychiatric problems later in life. In addition, the age at which such trauma occurred was likely to be important in influencing its long-term impact. Detailed data was therefore collected from enrolled women on traumatic events occurring during their own childhoods, along with their age at the time. The questionnaire entitled 'About Yourself' was sent out to expectant women who had enrolled in the study, which included a page in the form of a grid (an events diary) with one row per year of childhood and columns for recording where she was living at the time, who was looking after her, and any traumatic events that occurred. These free-text responses were then coded, and any events were assigned a score indicating the level of trauma the event was likely to have caused on a scale of 1 (highly traumatic) to 6 (least traumatic). This paper describes the variety of text data collected and how it was coded. The ALSPAC study has a great deal of follow-up data collected on the original respondents, as well as on their parents and grandparents, partners, offspring and their grandchildren, providing huge potential for analyses on the antecedents and outcomes of adverse childhood events across multiple generations.
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Mainstream religious beliefs and behaviours have been shown to have positive effects on health and well-being, but there has been increasing secularisation in the West over time. With concurrent increases in those stating they have no religion (the 'nones') there are increasing numbers now describing themselves as humanist, 'spiritual but not religious' or who have sought alternative forms of belief. Others have formed their own beliefs using elements of different belief systems. This trend is reflected in ALSPAC data with larger proportions considering themselves as 'nones', agnostic or atheist, and about 3% of parent participants consistently stating they had 'other' beliefs. The main aim of this paper is to describe the coding of the Christian denominations, world religions, non-mainstream beliefs (NMB) and non-religious groups derived from the text-based data collected from the original mother and partner cohorts (G0). This spans a period of ~28 years from pregnancy onwards. We also describe the coding of text-based responses from their offspring (G1) collected at ages 27+ and 29+. The creation of this coded data will enable researchers to compare between the Christian denominations and/or other belief groups taken from two generations alongside the rich resource of physical and mental health, behavioural and social data that exists within ALSPAC.
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BACKGROUND: The COVID-19 pandemic resulted in increased rates of mental health problems. We examined the possible role of the personality characteristic, Locus of Control (LOC), in moderating pandemic-induced stress. METHODS: The UK-based Avon Longitudinal Study of Parents & Children (ALSPAC), 7021 adults (mean ages: women 57.6 (SD = 4.48); partners 60.5 (SD = 5.36)) responded to a 2020 questionnaire which included a generalised measure of LOC. Between March 2020-January 2021, questionnaires focussed on the pandemic were administered, which included measures of mental health. Over 60 % of respondents completed questionnaires at three timepoints of interest. RESULTS: In those with an internal LOC higher rates of positive well-being and reduced likelihood of anxiety and depression were shown compared to those who were external, e.g. after adjustment for socioeconomic/demographic factors mean differences in well-being score for internal compared with external women was +2.01 (95%CI +1.02,+2.10) p = 0.0001; for their partners +2.52 (95%CI +1.22,+3.82) p = 0.0002. External women were more likely than internals to have depression (adjusted OR 3.41 [95%CI 1.77,6.57] p < 0.0005. LIMITATIONS: Attrition is a problem in this 30-year-old longitudinal cohort. Those still participating are more likely to have higher education and SES levels, be female and have an internal LOC. This population suffers from a lack of ethnic diversity. CONCLUSIONS: Having an internal LOC positively moderated the effects of pandemic-induced stress on the frequency of anxiety and depression in middle-age. Programmes geared to raise internality and coping strategies may have long-term benefits on well-being in stressful situations, especially for women and frontline health professionals.
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COVID-19 , Pandemias , Adulto , Pessoa de Meia-Idade , Criança , Humanos , Feminino , Estudos Longitudinais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Saúde Mental , Ansiedade/epidemiologia , Ansiedade/psicologia , Personalidade , Depressão/epidemiologia , Depressão/psicologiaRESUMO
Background: When studying the development of children through the preteen years into adolescence, it is often important to link features of their physical and mental health to the stage of puberty at the time. This is complex since individuals vary substantially in the ages at which they reach different pubertal milestones. Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is an ongoing longitudinal cohort study based in southwest England that recruited over 14000 women in pregnancy, with expected dates of delivery between April 1991 and December 1992. From 1999, information on puberty was collected using a number of different methods : (a) A series of annual questionnaires were administered when the index children were aged between eight and 17 years; these were mainly concerned with the physical changes associated with puberty; (b) identification of the age at peak height growth using the SITAR methodology; and (c) retrospective information from the girls on their age at onset of menstruation (menarche). Results: The advantages and disadvantages of each method are discussed. Conclusions: The data are available for analysis by interested researchers.
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OBJECTIVE: To determine whether early ear and upper respiratory signs are associated with the development of high levels of autistic traits or diagnosed autism. DESIGN: Longitudinal birth cohort: Avon Longitudinal Study of Parents and Children (ALSPAC). SETTING: Area centred on the city of Bristol in Southwest England. Eligible pregnant women resident in the area with expected date of delivery between April 1991 and December 1992 inclusive. PARTICIPANTS: 10 000+ young children followed throughout their first 4 years. Their mothers completed three questionnaires between 18-42 months recording the frequency of nine different signs and symptoms relating to the upper respiratory system, as well as ear and hearing problems. OUTCOME MEASURES: Primary-high levels of autism traits (social communication, coherent speech, sociability, and repetitive behaviour); secondary-diagnosed autism. RESULTS: Early evidence of mouth breathing, snoring, pulling/poking ears, ears going red, hearing worse during a cold, and rarely listening were associated with high scores on each autism trait and with a diagnosis of autism. There was also evidence of associations of pus or sticky mucus discharge from ears, especially with autism and with poor coherent speech. Adjustment for 10 environmental characteristics made little difference to the results, and substantially more adjusted associations were at p<0.001 than expected by chance (41 observed; 0.01 expected). For example, for discharge of pus or sticky mucus from ears the adjusted odds ratio (aOR) for autism at 30 months was 3.29 (95% CI 1.85 to 5.86, p<0.001), and for impaired hearing during a cold the aOR was 2.18 (95% CI 1.43 to 3.31, p<0.001). CONCLUSIONS: Very young children exhibiting common ear and upper respiratory signs appear to have an increased risk of a subsequent diagnosis of autism or demonstrated high levels of autism traits. Results suggest the need for identification and management of ear, nose and throat conditions in autistic children and may provide possible indicators of causal mechanisms.
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Transtorno Autístico , Humanos , Criança , Feminino , Gravidez , Pré-Escolar , Estudos Longitudinais , Estudos Prospectivos , Pais , SupuraçãoRESUMO
Introduction: Within human epidemiological studies, associations have been demonstrated between grandparental exposures during childhood and grandchildren's outcomes. A few studies have assessed whether asthma has ancestral associations with exposure to cigarette smoking, but results have been mixed so far. Material and methods: In this study we used four generations: (F0 great-grandparents, F1 grandparents, F2 parents, F3 study children) of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether there is evidence of associations between asthma in generations F2 or F3 and exposures to severe trauma in childhood and/or active cigarette smoking during the adolescence of grandmothers and grandfathers in generations F0 and F1 respectively, or of a history of a F0 or F1 grandmother smoking during pregnancy. Results: We have shown that: a) stress exemplified by the death of a F1 grandparent's parent during the grandparents' childhood was associated with increased risk of asthma in generation F3, especially if the grandparent involved was the paternal grandmother; b) if the grandparents of generations F0 or F1 smoked during adolescence (i.e. < 17 years), their grandchildren in generations F2 and F3 were more likely to have a history of asthma; c) paternal F1 grandmother's smoking in pregnancy was associated with her F3 grandchild's asthma at age 7; d) There were differences between the results for the grandsons and granddaughters of the paternal grandmother with exposure to smoking in adolescence and with smoking in pregnancy. e) The addition of all of the individual exposure variables to the different analyses often provided a considerable increase in goodness of fit compared with only adding demographic factors associated with asthma at P < 0.10 such as social class; this was particularly true when all four exposure variables were combined in one model, suggesting possible synergistic effects between them. Discussion: We have shown associations between all four types of exposure to the grandparents to be associated with asthma in the grandchildren, such that the results both depended on whether the male or female line was involved, and the sex of the grandchildren. It was notable that the paternal grandmother was particularly involved in many of the associations. We emphasize that these are exploratory analyses, that asthma diagnostic criteria likely changed over time and may not be consistent between generations, and that the results should be tested in other cohorts.
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Quality of relationship between partners is associated with a wide range of physical and psychological outcomes like anxiety and depression. There are relatively few longitudinal studies with detailed and repeated measures for quality of relationship, particularly in both partners. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a large birth cohort study in the UK with five post-partum repeated measures of quality of relationship between mothers and their partners assessed using the Intimate Bond Measure (IBM). The Measure includes two subscales named "Care" and "Control". These were measured at 2.75, 6, 9, 12, and 18 years post-partum (baseline N for mothers: 8675; baseline N for partners: 5499). The aims of this data note are to provide a comprehensive overview on the existing IBM data in ALSPAC and to describe both its strengths and limitations for future users. The internal consistency of the subscales were high (Cronbach's alpha 0.95 and 0.88 for the Care and Control subscales) in both mothers and their partners at the baseline. In the Care subscale, all 12 items were highly correlated with the overall score (r>0.62) at the baseline, but in the Control subscale there were three items that had relatively low correlations with the total subscale (r<0.46). This should be taken into account in future research. The longitudinal nature of this data on both mothers and partners will enable detailed explorations of the causes and consequences of differences in quality of relationship.
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Longitudinal data on religious/spiritual beliefs and behaviors (RSBB) are essential for understanding both how religion shapes our lives and the factors determining religiosity. Despite this importance, there are few longitudinal studies with detailed and repeated RSBB data. Using data spanning nearly 30 years from the parental generation of the Avon Longitudinal Study of Parents and Children (ALSPAC) based in the Southwest of England, we describe individual-level changes in various aspects of self-reported RSBB (religious belief, affiliation, and attendance, among others) measured on four occasions (pregnancy, plus 5, 9, and 28 years post-partum; approx. 3600 mothers and 1200 partners have data at all four time-points). Although RSBBs were generally consistent over time, a shift towards non-religiosity was observed; exceptions included Roman Catholic affiliation, which was remarkably stable over three decades, and religious attendance, which increased from pregnancy to 5 years, before declining at 28 years. Most changes in RSBB were minor, e.g., between "yes" and "not sure" regarding religious belief, rather than between "yes" and "no." We also provide a simple illustrative example of how these longitudinal data can be analyzed. In addition to describing these longitudinal patterns, this paper will help inform future research using ALSPAC's longitudinal RSBB data.
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Background: Early life environmental health exposures related to housing can have a significant impact on an individual's physical and mental health and physical development. Housing exposures can fall into two main areas - a representation of social circumstances and physical conditions. Methods: During pregnancy and post-delivery, self-completion questionnaires concerning the housing environment were administered to the ALSPAC (Avon Longitudinal Study of Parents & Children) study mothers and their partners until the study offspring were aged 18. Data collected included types of housing, housing tenure, numbers of rooms in the home, whether shared or sole use of kitchen and indoor flushing toilet, household moves, Council Tax band, difficulties in affording rent/mortgage and becoming homeless. Here we also describe the historic development of housing in the Bristol and surrounding Avon areas. Results: Data collected included the tenure (e.g., owned/rented) of the home, its size (indexed by the number of rooms), the presence of over-crowding (measured by the number of residents per room), presence of amenities, and frequency of household moves. This information was collected on over 13,000 women during pregnancy >8000 at age 10 and >4000 at 18 years. Council Tax bands were asked at 10 and 18 years. Conclusions: This is the first of two Data Notes on the housing type and housing circumstances of the families enrolled in ALSPAC. The second Data Note will detail their internal housing conditions. The data provides an excellent resource for researchers when considering the influences of housing on physical and mental health and development.
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Health advice to pregnant women concerning consumption of mercury-containing foods has resulted in anxiety, with subsequent avoidance of fish consumption during pregnancy. However, seafood contains many nutrients crucial for children's growth and development. Longitudinal studies in the Seychelles, where fish is a major component of the diet, have not demonstrated harmful cognitive effects in children with increasing maternal mercury levels. Is the same true in a more developed country (the UK) where fish is eaten less frequently? We review publications using data collected by the Avon Longitudinal Study of Parents and Children (ALSPAC) to address this topic. Total mercury levels were measured in maternal whole blood and umbilical cord tissue. Offspring were followed throughout childhood, especially their cognitive development. No adverse associations were noted. Significantly beneficial associations with prenatal mercury levels were shown for total and performance IQ, mathematical/scientific reasoning, and birthweight in fish-consuming vs non-fish consuming mothers. These beneficial findings are similar to those observed in the Seychelles where fish consumption is high and prenatal Hg levels are x10 higher than US levels. Government recommendations should be reviewed to emphasise the beneficial value of fish consumption during pregnancy. DATA AVAILABILITY: ALSPAC data access is through a system of managed open access. The steps below highlight how to apply for access to the data included in this paper and all other ALSPAC data. If you have any questions about accessing data, please email: alspac-data@bristol.ac.uk.
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Mercúrio , Efeitos Tardios da Exposição Pré-Natal , Animais , Desenvolvimento Infantil , Estudos de Coortes , Feminino , Peixes , Contaminação de Alimentos , Humanos , Estudos Longitudinais , Exposição Materna/efeitos adversos , Mercúrio/análise , Gravidez , Alimentos Marinhos/efeitos adversosRESUMO
Within the ALSPAC (Avon Longitudinal Study of Parents and Children) resource, information concerning the health of the mother during pregnancy is available from three sources: (i) computerised data collected by midwives after the delivery of the baby, known as the STORK database; (ii) data abstracted by ALSPAC staff from detailed medical obstetric records, and (iii) reports by mothers during pregnancy, and shortly after delivery using structured questionnaires completed at home. In this Data Note we focus on source (iii), and detail the information obtained from these mothers concerning their health, signs and symptoms together with medications and supplements taken during pregnancy. We also describe how the data can be accessed.
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Background: Previous studies using the Avon Longitudinal Study of Parents and Children (ALSPAC) have shown that if men commenced smoking prior to the onset of puberty their sons, their granddaughters and great-granddaughters were more likely to have excess fat (but not lean) mass during childhood, adolescence and early adulthood. In this study we assess associations between ancestral smoking during adolescence (ages 11-16 years) with fat and lean mass of subsequent generations at two ages. Methods: We analysed data on exposures of grandparents and great-grandparents collected by ALSPAC. The outcomes were the fat masses of their grandchildren and great-grandchildren measured at ages 17 and 24. Measures of lean mass were used as controls. Adjustment was made for 8-10 demographic factors using multiple regression. Results: We found associations between adolescent smoking of the paternal grandfathers and the adjusted fat mass of their grandchildren, but no associations with the grandchildren's lean mass. Grandchildren at age 17 had an average excess fat mass of +1.65 [95% CI +0.04, +3.26] Kg, and at age 24 an average excess of +1.55 [95% CI -0.27, +3.38] Kg. Adolescent smoking by the maternal grandfather showed similar, but weaker, associations: at 17 an average excess fat mass of +1.02 Kg [95% CI -0.20, +2.25] Kg, and at 24 an average excess of +1.28 [95% CI -0.11, +2.66] Kg. There were no pronounced differences between the sexes of the children. For the great-grandparents there were few convincing results, although numbers were small. Conclusions: We have shown associations between grandfathers' smoking in adolescence and increased fat (but not lean) mass in their children. Confirmation of these associations is required, either in a further data set or by demonstrating the presence of supportive biomarkers.
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Previously, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we showed that sons of fathers who had started smoking regularly before puberty (< 13 years) had increased fat mass during childhood, adolescence, and early adulthood. We now show that if the paternal grandfather had started smoking pre-puberty, compared with later in childhood (13-16 years), his granddaughters, but not grandsons, had evidence of excess fat mass at two ages: mean difference + 3.54 kg; (P with 1-tailed test) = 0.043 at 17 years, and + 5.49 kg; (P1 = 0.016) at age 24. When fathers of maternal grandfathers had started smoking pre-puberty, their great-granddaughters, but not great-grandsons, had excess body fat: + 5.35 kg (P1 = 0.050) at 17, and + 6.10 kg (P1 = 0.053) at 24 years. Similar associations were not found with lean mass, in a sensitivity analysis. To determine whether these results were due to the later generations starting to smoke pre-puberty, further analyses omitted those in subsequent generations who had smoked regularly from < 13 years. The results were similar. If these associations are confirmed in another dataset or using biomarkers, this will be one of the first human demonstrations of transgenerational effects of an environmental exposure across four generations.
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Adiposidade/fisiologia , Avós , Pais , Fumar/epidemiologia , Adolescente , Criança , Humanos , Estudos Longitudinais , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/fisiopatologia , Fatores de Tempo , Adulto JovemRESUMO
The idea that information can be transmitted to subsequent generation(s) by epigenetic means has been studied for decades but remains controversial in humans. Epidemiological studies have established that grandparental exposures are associated with health outcomes in their grandchildren, often with sex-specific effects; however, the mechanism of transmission is still unclear. We conducted Epigenome Wide Association Studies (EWAS) to test whether grandmaternal smoking during pregnancy is associated with altered DNA methylation (DNAm) in peripheral blood from their adolescent grandchildren. We used data from a birth cohort, with discovery and replication datasets of up to 1225 and 708 individuals (respectively, for the maternal line), aged 15-17 years, and tested replication in the same individuals at birth and 7 years. We show for the first time that DNAm at a small number of loci in cord blood is associated with grandmaternal smoking in humans. In adolescents we see suggestive associations in regions of the genome which we hypothesised a priori could be involved in transgenerational transmission - we observe sex-specific associations at two sites on the X chromosome and one in an imprinting control region. All are within transcription factor binding sites (TFBSs), and we observe enrichment for TFBS among the CpG sites with the strongest associations; however, there is limited evidence that the associations we see replicate between timepoints. The implication of this work is that effects of smoking during pregnancy may induce DNAm changes in later generations and that these changes are often sex-specific, in line with epidemiological associations.
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Metilação de DNA , Fumar , Recém-Nascido , Gravidez , Masculino , Adolescente , Feminino , Humanos , Fumar/genética , Epigênese Genética , Estudo de Associação Genômica Ampla , FamíliaRESUMO
Although there are many examples in the experimental literature of an environmental exposure in one generation impacting the phenotypes of subsequent generations, there are few studies that can assess whether such associations occur in humans. The Avon Longitudinal Study of Parents and Children (ALSPAC) has, however, been able to determine whether there are associations between grandparental exposures and their grandchildren's development. Several of our studies, including sensitivity to loud noise, have shown associations between a grandmother smoking in pregnancy and the phenotype of the grandchild. These results were mostly specific to the sex of the grandchild and to whether the prenatal (i.e. during pregnancy) smoking occurred in the maternal or paternal grandmother. Here, we have used ancestral data on prenatal smoking among the grandmothers of the ALSPAC index children to examine possible effects on the grandchild's ability to detect the bitter taste of PROP (6 n-propylthiouracil), distinguishing between the 10% deemed 'extreme tasters', and the rest of the population (total N = 4656 children). We showed that grandchildren whose paternal (but not maternal) grandmothers had smoked in pregnancy were more likely than those of non-smoking grandmothers to be extreme tasters [odds ratio (OR) 1.28; 95% confidence interval (CI) 1.03, 1.59] and that this was more likely in granddaughters (OR 1.42; 95% CI 1.03, 1.95) than grandsons (OR 1.18; 95% CI 0.88, 1.60). This pattern of association between paternal foetal exposure and the granddaughter's development has been found with several other outcomes, suggesting that investigations should be undertaken to investigate possible mechanisms.