The iceberg model of suicidal ideation and behaviour in Danish adolescents: integration of national registry and self-reported data within a national birth cohort.

Hospital records are used to identify suicide attempts in many countries but not all individuals present to hospital after a suicide attempt i.e., suggesting a 'hidden number'. Our aim was to present the prevalence of suicide ideation, plans, attempts, and suicides among Danish adolescents, including attempts not resulting in hospital contact. The study population consisted of participants in the Danish National Birth Cohort participating in an 18-year follow-up, with individual-level linkage to national register data. Prevalence was estimated with a variable with mutually exclusive categories ranging from no suicidality to self-reported suicide ideation, -plans, -attempt and hospital-recorded suicide attempt and stratified on sex and parental income. The 'hidden number' was estimated as the ratio between suicide attempts with and without hospital contact. Among 47 858 participants, all aged 18-years, 36% girls and 28% boys reported suicide ideation at least once in their life. In addition, 6% girls and 3% boys had either reported or been recorded with a suicide attempt. For every attempt recorded in the hospital setting, two girls (ratio, 1:2) and six boys (ratio, 1:6) reported having attempted suicide without hospital contact. The prevalence of any suicide attempt was 8% and 3% in the lowest and highest income group, respectively. Before age 18, 0·011% girls and 0·016% boys had died by suicide. In conclusion, suicidal ideation and behaviour are common in adolescents and there is a substantial 'hidden number' of adolescents with suicide attempt. These results emphasize the need for early age suicide preventive interventions in community-settings e.g., school environments.

Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. METHODS AND FINDINGS: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. CONCLUSIONS: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

Correction: Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

Maternal Tobacco Smoking During Pregnancy and Children's Emotional and Behavioral Trajectories: The EDEN Mother-Child Birth Cohort Study.

INTRODUCTION: The nature of the relationship between maternal tobacco smoking during pregnancy and the occurrence of children's behavioral problems is still a matter of controversy. We tested this association using data collected among a sample of pregnant women and their offspring followed up from birth to early adolescence (age 12 years), accounting for multiple parent, child, and family characteristics. AIMS AND METHODS: Data come from 1424 mother-child pairs participating in the Étude des Déterminants pré et post-natals précoces du développement psychomoteur et de la santé de l'ENfant mother-child cohort in France. Using repeated measures (3, 5.5, 8, and 11.5 years) of the mother-reported Strengths and Difficulties Questionnaire, we estimated trajectories of children's emotional and behavioral difficulties. Two aspects of maternal smoking were studied: The timing (nonsmoker, smoking during the periconceptional period, or throughout pregnancy) and the level of use (cigarettes/day) during the first trimester of pregnancy. Robust Poisson regression models controlled for confounding factors including maternal mental health and socioeconomic characteristics using propensity scores with the overlap weighting technique. RESULTS: Contrary to bivariate analyses, in propensity score-controlled regression models, maternal smoking throughout pregnancy was no longer significantly associated with offspring emotional or behavioral difficulties. Maternal heavy smoking (≥10 cigarettes/day) remained significantly associated with intermediate levels of conduct problems (RR 1.25, 95% CI 1.19 to 1.31). CONCLUSIONS: The association between maternal smoking in pregnancy and offspring's emotional and behavioral difficulties appears to be largely explained by women's other characteristics. However, maternal heavy smoking appears to be related to offspring behavioral difficulties beyond the role of confounding characteristics. IMPLICATIONS: The relationship between maternal smoking during pregnancy (in two modalities: Timing and level of smoking) and behavioral difficulties in children is still a matter of debate. While the relationship between any maternal tobacco use and offspring behavioral difficulties appears to be largely explained by confounding factors, heavy maternal smoking in the first trimester of pregnancy seems to be associated with offspring behavioral difficulties beyond the socioeconomic and mental health characteristics transmitted across generations.

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.

BACKGROUND: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. METHODS: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. RESULTS: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. CONCLUSION: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Childhood body mass index and the subsequent risk of anorexia nervosa and bulimia nervosa among women: A large Danish population-based study.

OBJECTIVE: Evidence linking childhood body mass index (BMI) with subsequent eating disorders is equivocal. Potential explanations include different study populations and size, and that anorexia nervosa (AN) and bulimia nervosa (BN) should be studied separately. We examined whether birthweight and childhood BMI were associated with subsequent risk of AN and BN in girls. METHOD: We included 68,793 girls from the Copenhagen School Health Records Register born between 1960 and 1996 with information on birthweight and measured weights and heights obtained from school health examinations at ages 6-15 years. Diagnoses of AN and BN were retrieved from Danish nationwide patient registers. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 355 cases of AN (median age: 19.0) and 273 cases of BN (median age: 21.8). Higher childhood BMI was linearly associated with decreasing risk of AN and increasing risk of BN at all childhood ages. At age 6, the HR for AN was 0.85 (95% CI: 0.74-0.97) per BMI z-score and the HR for BN was 1.78 (95% CI: 1.50-2.11) per BMI z-score. Birthweight >3.75 kg was associated with increased risk of BN compared to a birthweight of 3.26-3.75 kg. CONCLUSION: Higher BMI in girls at ages 6-15 years was associated with decreasing risk of AN and increasing risk of BN. Premorbid BMI could be relevant for the etiology of AN and BN, and in identifying high risk individuals. PUBLIC SIGNIFICANCE: Eating disorders are associated with elevated mortality, especially AN. Using a cohort of Copenhagen school children, we linked information on BMI at ages 6-15 years for 68,793 girls with nationwide patient registers. Low childhood BMI was associated with increased risk of AN, whereas high childhood BMI was associated with increased risk of BN. These findings may assist clinicians in identifying individuals at high-risk of these diseases.

Comparison of prevalence and mental health problems across symptom frequency of self-reported symptoms of binge-eating disorder in a community sample of adolescents.

OBJECTIVE: Binge-eating disorder (BED) and subthreshold BED (SBED) are prevalent in adults and associated with mental health problems including depression, non-suicidal self-injury, lower quality of life, and suicidality. There is solid evidence that binge-eating behaviors are also prevalent in adolescence, but knowledge about mental health in community adolescents with BED of different frequency thresholds is more limited. We aimed to investigate the prevalence and mental health problems associated with SBED of low frequency and/or limited duration compared with BED in a Danish community sample of adolescents. METHODS: We included 2509 adolescents who completed the online survey of the 16-17-year follow-up of the Copenhagen Child Cohort (CCC2000), including items on BED symptoms approximating the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and items on mental health and quality of life. RESULTS: The 1-year prevalence of SBED was 2.7% (95% confidence interval [CI]: 2.0%-3.3%) with a male:female ratio of 1:3.7; comparable to previous findings on BED in the same sample. SBED was also comparable to BED concerning cross-sectional associations with overall mental health problems, lower health-related quality of life, depressive symptoms, and suicidal ideation, whereas no associations were seen with non-suicidal self-injury after Holm-Bonferroni correction. In both groups, thoughts and behaviors concerning food and weight interfered significantly with daily life. DISCUSSION: SBED and BED were equally prevalent in this adolescent community sample, and similarly associated with indicators of poor mental health. The findings indicate that community adolescents reporting symptoms approximating clinical criteria of BED need intervention irrespectively of symptom frequency or duration. PUBLIC SIGNIFICANCE: This study adds knowledge to the field by comparing BED of low frequency and/or limited duration ("subthreshold BED," SBED) with full-syndrome BED in adolescents and showing that SBED in adolescence is both prevalent and associated with poor mental health to a similar extent as that of BED. Findings indicate that self-reported symptoms according to clinical criteria of SBED and BED alike constitute a public health problem and point to youngsters in need of intervention.

Maternal alcohol consumption and the risk of miscarriage in the first and second trimesters: A systematic review and dose-response meta-analysis.

INTRODUCTION: According to a precautionary principle, it is recommended that pregnant women and women trying to conceive abstain from alcohol consumption. In this dose-response meta-analysis, we aimed to examine the association between alcohol consumption and binge drinking and the risk of miscarriage in the first and second trimesters. MATERIAL AND METHODS: The literature search was conducted in MEDLINE, Embase and the Cochrane Library in May 2022, without any language, geographic or time limitations. Cohort or case-control studies reporting dose-specific effects adjusting for maternal age and using separate risk assessments for first- and second-trimester miscarriages were included. Study quality was assessed using the Newcastle-Ottawa Scale. This study is registered with PROSPERO, registration number CRD42020221070. RESULTS: A total of 2124 articles were identified. Five articles met the inclusion criteria. Adjusted data from 153 619 women were included in the first-trimester analysis and data from 458 154 women in the second-trimester analysis. In the first and second trimesters, the risk of miscarriage increased by 7% (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96-1.20) and 3% (OR 1.03, 95% CI 0.99-1.08) for each additional drink per week, respectively, but not to a statistically significant degree. One article regarding binge drinking and the risk of miscarriage was found, which revealed no association between the variables in either the first or second trimester (OR 0.84 [95% CI 0.62-1.14] and OR 1.04 [95% CI 0.78-1.38]). CONCLUSIONS: This meta-analysis revealed no dose-dependent association between miscarriage risk and alcohol consumption, but further focused research is recommended. The research gap regarding miscarriage and binge drinking needs further investigation.

Effectiveness of a community-based support programme to reduce social inequality in exclusive breastfeeding: study protocol for a cluster-randomised trial.

BACKGROUND: Breastmilk is the ideal nutrition for infants, and breastfeeding protects infants and mothers from a range of adverse health outcomes. In Denmark, most mothers initiate breastfeeding but many cease within the first months resulting in just 14% reaching the World Health Organization recommendation of six months of exclusive breastfeeding. Furthermore, the low breastfeeding proportion at six months is characterised by a marked social inequality. A previous intervention tested in a hospital setting succeeded in increasing the proportion of mothers breastfeeding exclusively at six months. However, most breastfeeding support is provided within the Danish municipality-based health visiting programme. Therefore, the intervention was adapted to fit the health visiting programme and implemented in 21 Danish municipalities. This article reports the study protocol, which will be used to evaluate the adapted intervention. METHODS: The intervention is tested in a cluster-randomised trial at the municipal level. A comprehensive evaluation approach is taken. The effectiveness of the intervention will be evaluated using survey and register data. Primary outcomes are the proportion of women who breastfeed exclusively at four months postpartum and duration of exclusive breastfeeding measured as a continuous outcome. A process evaluation will be completed to evaluate the implementation of the intervention; a realist evaluation will provide an understanding of the mechanisms of change characterising the intervention. Finally, a health economic evaluation will assess the cost-effectiveness and cost-utility of this complex intervention. DISCUSSION: This study protocol reports on the design and evaluation of the Breastfeeding Trial - a cluster-randomised trial implemented within the Danish Municipal Health Visiting Programme from April 2022 to October 2023. The purpose of the programme is to streamline breastfeeding support provided across healthcare sectors. The evaluation approach is comprehensive using a multitude of data to analyse the effect of the intervention and inform future efforts to improve breastfeeding for all. TRIAL REGISTRATION: Prospectively registered with Clinical Trials NCT05311631 https://clinicaltrials.gov/ct2/show/NCT05311631.

Body height and spinal pain in adolescence: a cohort study from the Danish National Birth Cohort.

OBJECTIVES: To investigate how body height and trajectories of height from infancy through childhood and adolescence were associated with spinal pain in pre- and late adolescence. METHODS: This prospective study included 43,765 individuals born into The Danish National Birth Cohort (DNBC) from 1996 to 2003. DNBC-data were linked with health and social data identified from Statistics Denmark registers. Spinal pain was self-reported in both the 11-year- and 18-year follow-up of DNBC and classified according to severity. Body height was measured from birth and onwards and further modelled as distinct developmental height trajectories by using latent growth curve modelling. Associations were estimated by using multinomial logistic regression models. RESULTS: Taller body height in childhood and adolescence was associated with approximately 20% increased likelihood of spinal pain in pre- and late adolescence among girls compared to their peers in the normal height group. For boys, taller body height was associated with spinal pain by late adolescence only. Spinal pain in pre-adolescence almost doubled the likelihood of spinal pain in late adolescence regardless of body height at age 18. Height trajectories confirmed the relationship for girls with the tall individuals being most likely to have spinal pain in both pre- and late adolescence. CONCLUSION: Tall body height during childhood and adolescence predisposes to spinal pain among girls in both pre-and late adolescence, and among boys in late adolescence. Body height is a contributing factor to the pathogenesis of spinal pain in adolescence; however, the mechanisms may be related to growth velocity, but for now uncertain.

Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network.

BACKGROUND: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. OBJECTIVE: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. METHODS: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. RESULTS: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. CONCLUSION: Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.

A critical examination of Danish norms for the Strengths and Difficulties Questionnaire (SDQ).

OBJECTIVE: The objective was to describe observed differences between the official Danish Strengths and Difficulties Questionnaire (SDQ)-norms and data from a sample based on the Danish National Birth Cohort (DNBC) including children born between 1996 and 2003. We compared the risk classification, cut-off bandings and the group sizes between the Danish norms and the values found in our sample at ages 7, 11 and 18 years. RESULTS: Two sets of norms are used in Denmark: Arnfred's norms, based on a sample from one single Danish municipality and Niclasen's norms, based on multiple Danish cohorts, including the DNBC. Inconsistencies were found between banding scores in the two existing norms and the banding scores identified in our sample from DNBC: discrepancies included banding scores for several of the problem scales for children and preadolescents. For adolescents, we found less apparent inconsistencies between Arnfred's sample and the DNBC. Results demonstrate that the existing SDQ norms do not apply well to a large-scale cohort sample in Denmark. The usefulness of the SDQ as a screening instrument for mental health problems depends on appropriate norms. We therefore urge that the current Danish SDQ norms are used with caution, and preferably they should be revised.

Epigenome-Wide Associations of Placental DNA Methylation and Behavioral and Emotional Difficulties in Children at 3 Years of Age.

The placenta is a key organ for fetal and brain development. Its epigenome can be regarded as a biochemical record of the prenatal environment and a potential mechanism of its association with the future health of the fetus. We investigated associations between placental DNA methylation levels and child behavioral and emotional difficulties, assessed at 3 years of age using the Strengths and Difficulties Questionnaire (SDQ) in 441 mother-child dyads from the EDEN cohort. Hypothesis-driven and exploratory analyses (on differentially methylated probes (EWAS) and regions (DMR)) were adjusted for confounders, technical factors, and cell composition estimates, corrected for multiple comparisons, and stratified by child sex. Hypothesis-driven analyses showed an association of cg26703534 (AHRR) with emotional symptoms, and exploratory analyses identified two probes, cg09126090 (intergenic region) and cg10305789 (PPP1R16B), as negatively associated with peer relationship problems, as well as 33 DMRs, mostly positively associated with at least one of the SDQ subscales. Among girls, most associations were seen with emotional difficulties, whereas in boys, DMRs were as much associated with emotional than behavioral difficulties. This study provides the first evidence of associations between placental DNA methylation and child behavioral and emotional difficulties. Our results suggest sex-specific associations and might provide new insights into the mechanisms of neurodevelopment.

Time trends in mental health indicators during the initial 16 months of the COVID-19 pandemic in Denmark.

BACKGROUND: The COVID-19 pandemic and its associated national lockdowns have been linked to deteriorations in mental health worldwide. A number of studies analysed changes in mental health indicators during the pandemic; however, these studies generally had a small number of timepoints, and focused on the initial months of the pandemic. Furthermore, most studies followed-up the same individuals, resulting in significant loss to follow-up and biased estimates of mental health and its change. Here we report on time trends in key mental health indicators amongst Danish adults over the course of the pandemic (March 2020 - July 2021) focusing on subgroups defined by gender, age, and self-reported previously diagnosed chronic and/or mental illness. METHODS: We used time-series data collected by Epinion (N=8,261) with 43 timepoints between 20 March 2020 and 22 July 2021. Using a repeated cross-sectional study design, independent sets of individuals were asked to respond to the Copenhagen Corona-Related Mental Health questionnaire at each timepoint, and data was weighted to population proportions. The six mental health indicators examined were loneliness, anxiety, social isolation, quality of life, COVID-19-related worries, and the mental health scale. Gender, age, and the presence of previously diagnosed mental and/or chronic illness were used to stratify the population into subgroups for comparisons. RESULTS: Poorer mental health were observed during the strictest phases of the lockdowns, whereas better outcomes occurred during reopening phases. Women, young individuals (<34 yrs), and those with a mental- and/or chronic illness demonstrated poorer mean time-series than others. Those with a pre-existing mental illness further had a less reactive mental health time-series. The greatest differences between women/men and younger/older age groups were observed during the second lockdown. CONCLUSIONS: People with mental illness have reported disadvantageous but stable levels of mental health indicators during the pandemic thus far, and they seem to be less affected by the factors that result in fluctuating time-series in other subgroups.

Risk of breast cancer in Danish women occupationally exposed to organic solvents, including ethanol.

BACKGROUND: Organic solvents have been suggested to increase the risk of breast cancer although the epidemiologic evidence is limited. This study explored the association between organic solvents and breast cancer. METHODS: This nested population-based case-control study comprised 845 women with primary breast cancer initially identified in the Danish Cancer Registry between 2000 and 2003, and 1500 controls matched on year of birth who were randomly selected from the Danish Civil Registration System. Information on occupational exposure to organic solvents, and specifically ethanol, as well as risk factors for breast cancer was collected through structured interviews. RESULTS: For organic solvents, an increased risk was indicated for ever-exposure (odds ratio = 3.20, 95% confidence interval: 2.27-4.52), however, no noteworthy risk patterns were detected when exploring duration of exposure and cumulative exposure. Ever-exposure to organic solvents was associated with an increased risk of estrogen receptor negative and positive tumors as well as pre- and postmenopausal breast cancer. No associations were detected between occupational exposure to ethanol and breast cancer. CONCLUSIONS: This study indicates a positive association between organic solvents and breast cancer.

Behavioral Problems at Age 11 Years After Prenatal and Postnatal Exposure to Acetaminophen: Parent-Reported and Self-Reported Outcomes.

Several studies have reported associations between prenatal acetaminophen exposure and behavioral outcomes in young children. We aimed to evaluate the associations of prenatal and postnatal exposures to acetaminophen with behavioral problems in children at age 11 years, using behavioral measures reported by parents and children. We studied 40,934 mother-child pairs from the Danish National Birth Cohort enrolled during 1996-2002. Parent-reported and child-reported Strengths and Difficulties Questionnaire (SDQ) responses were collected during the 11-year follow-up. We estimated risk ratios for behavioral problems including total difficulties as well as internalizing or externalizing behaviors following prenatal (during pregnancy) or postnatal (within the first 18 months after birth) acetaminophen exposure. Parent-reported and child-reported SDQ scores were moderately correlated; higher for externalizing (r = 0.59) than internalizing (r = 0.49) behaviors. Prenatal acetaminophen exposure was associated with 10%-40% higher risks for total difficulties and internalizing and externalizing problems based on parent- or child-reported SDQ, with the association being stronger for greater cumulative weeks of acetaminophen use. Postnatal exposure was associated with 16%-19% higher risks for parent-reported internalizing behaviors, but the associations were weak or null for child-reported scores except for prosocial behavior. Our study corroborates published associations between prenatal exposures to acetaminophen and behavioral problems and extends the literature to early adolescence.

Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

The EU Child Cohort Network's core data: establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables.

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.

Occupational exposure to solar ultraviolet B radiation and risk of subtypes of breast cancer in Danish women.

OBJECTIVES: Previous epidemiological studies have indicated that solar ultraviolet B radiation (UVR) may have a protective effect on breast cancer. However, the evidence remains inconclusive. Despite the fact that outdoor work history may be considered a reliable measure of long-term UVR exposure, objective information on lifetime employment has not been included in previous investigations focusing on breast cancer. To address this issue, we explored the association between occupational UVR exposure and female breast cancer, including subtypes. METHODS: A total of 38 375 women under the age of 70 years were identified with primary breast cancer using the Danish Cancer Registry. Five female controls born on the same year, alive and free of breast cancer at the time of diagnosis of the index case, were randomly selected from the Danish Civil Registration System. The Danish Supplementary Pension Fund Register was used to retrieve full employment history, and a job exposure matrix was used to assess occupational UVR exposure. Conditional logistic regression with adjustment for important confounders was used to estimate the OR. RESULTS: We observed no overall association between occupational UVR exposure and breast cancer. After the age of 50 years, longer duration of UVR exposure (≥20 years: OR=0.83, 95% CI 0.75 to 0.92) and highest cumulative exposure (OR=0.89, 95% CI 0.83 to 0.95) were inversely associated with risk. Our results did not reflect any notable risk difference by oestrogen receptor status. CONCLUSIONS: This study indicates an inverse association between long-term occupational UVR exposure and late-onset breast cancer. This finding needs further attention in future occupational studies.

Self-reported symptoms of binge-eating disorder among adolescents in a community-based Danish cohort-A study of prevalence, correlates, and impact.

OBJECTIVE: Binge-eating disorder (BED) was established as a diagnosis in 2013 with the DSM-5 and has been included in the ICD-11 in 2018. In adulthood, BED is prevalent and correlated with somatic and mental health problems. Less is known about BED in adolescence, although this age period could represent a window of opportunity for early intervention. This study aimed to investigate the 1-year prevalence, correlates, and impact of BED symptoms in a community sample of adolescents. METHOD: We included 1,404 girls and 1,105 boys from the 16-years-follow-up of the Copenhagen Child Cohort study, CCC2000. The adolescents self-reported on BED symptoms, weight-status, body perception, mental health problems, and self-rated impact of food and weight-related thoughts and behaviors. Information about socio-economic factors and hospital diagnosed psychiatric disorders were obtained from national registries. RESULTS: A total of 8.5% reported weekly overeating with loss of control (10.9% of girls, 4.8% of boys), and 2.6% (3.6% of girls, 1.2% of boys) reported symptoms consistent with BED according to the DSM-5. Regardless of sex, BED was correlated with concurrent overweight, body-dissatisfaction, low self-esteem, and mental health problems, especially emotional, but also with problems of behavior, inattention, and peer-relations, and with high self-rated impact on everyday life. Immigrant background and lower socio-economy were potential risk factors for BED in boys in this sample. DISCUSSION: BED was prevalent and correlated with mental health problems and overall impact among adolescents in this community sample, indicating the need for clinical attention and intervention towards binge-eating disorder in the adolescent period.