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Abstract Background External causes of death, such as accidents, substance use, and suicide, contribute substantially to mortality during adolescence and early adulthood and show marked sex differences. Individuals born preterm are at increased risk of mental disorders, and impaired cognitive and executive functions, potentially increasing their vulnerability to death from external causes. We investigated sex-specific associations between gestational age at birth and mortality from external causes during late adolescence and early adulthood. Methods Individual level data from national health registries in Denmark (1978–2001), Finland (1987–2003), Norway (1967–2002), and Sweden (1974–2001) were linked to form nationwide cohorts. In total, 6,924,697 participants were followed from age 15 years to a maximum of 50 years in 2016–2018. Gestational age was categorized as “very/moderately preterm” (23–33 weeks), “late preterm” (34–36 weeks), “early term” (37–38 weeks), “full term” (39–41 weeks), and “post term” (42–44 weeks). Outcomes were mortality from external causes overall and from the largest subgroups transport accidents, suicide, and drugs or alcohol. We estimated sex-specific hazard ratios (HRs), with full term as the reference, and pooled each country’s estimates in meta-analyses. Results Across gestational ages mortality was higher for males than females. Individuals born very/moderately preterm had higher mortality from external causes, with HRs 1.11 (95% confidence interval [CI] 0.99–1.24) for males and 1.55 (95% CI 1.28–1.88) for females. Corresponding estimates for late preterm born were 1.11 (95% CI 1.04–1.18) and 1.15 (95% CI 1.02–1.29), respectively. Those born very/moderately preterm had higher mortality from transport accidents, but precision was low. For females, suicide mortality was higher following very/moderately preterm birth (HR 1.76, 95% CI 1.34–2.32), but not for males. Mortality from drugs or alcohol was higher in very/moderately and late preterm born males (HRs 1.23 [95% CI 0.99–1.53] and 1.29 [95% CI 1.16–1.45], respectively) and females (HRs 1.53 [95% CI 0.97–2.41] and 1.35 [95% CI 1.07–1.71], respectively, with some heterogeneity across countries). Conclusions Mortality from external causes overall was higher in preterm than full term born among both males and females. A clear sex difference was seen for suicide, where preterm birth was a risk factor in females, but not in males.

Objectives To understand how we can better initiate and run international collaborations to deliver tangible and impactful findings using population-wide linked health and education data. Approach Representatives from 14 countries (America, Australia, Canada, Chile, Denmark, England, Finland, Germany, New Zealand, Northern Ireland, Norway, Scotland, Sweden, Wales) summarised the potential for research using their linked administrative health and education data. The scope for collaboration and comparison of research findings across countries was explored. Results Several substantive research themes emerged, including the quantifying of differences in educational outcomes by health conditions and other early life factors, using health data to better identify and explore the special educational needs identified in educational records, using linked health and education data to identify and explore reasons for absenteeism from school. Conclusions The workshop showcased the primary themes for research and the data assets available within each country for comparative work. Further work is required to more robustly document the available detail within these datasets, collaboratively develop protocol templates for comparative studies, and develop pilot, proof of concept, studies.

Background Atopic diseases, obesity and neuropsychiatric disorders are lifestyle-related and environmental-related chronic inflammatory disorders, and the incidences have increased in the last years.Objective To outline the design of the 18-year follow-up of the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort, where risk factors of atopic diseases, obesity and neuropsychiatric disorders are identified through extensive characterisation of the environment, along with deep clinical phenotyping and biosampling for omics profiling.Methods COPSAC2000 is a Danish prospective clinical birth cohort study of 411 children born to mothers with asthma who were enrolled at 1 month of age and closely followed at the COPSAC clinical research unit through childhood for the development of atopic diseases. At the 18-year follow-up visit, biomaterial (hair, blood, urine, faeces, throat, and skin swabs, nasal lining fluid and scraping, and hypopharyngeal aspirates) and extensive information on environmental exposures and risk behaviours were collected along with deep metabolic characterisation and multiorgan investigations including anthropometrics, heart, lungs, kidneys, intestines, bones, muscles and skin. Neuropsychiatric diagnoses were captured from medical records and registers accompanied by electronic questionnaires on behavioural traits and psychopathology.Results A total of 370 (90%) of the 411 cohort participants completed the 18-year visit. Of these, 25.1% had asthma, 23.4% had a body mass index >25 kg/m2 and 16.8% had a psychiatric diagnosis in childhood. A total of 68.7% drank alcohol monthly, and when drinking, 22.2% drank >10 units. Of the participants, 31.4% were currently smoking, and of these, 24.1% smoked daily. A total of 23.8% had tried taking drugs, and 19.7% reported having done self-destructive behaviour. The mean screen time per day was 6.0 hours.Conclusion This huge dataset on health and habits, exposures, metabolism, multiorgan assessments and biosamples from COPSAC2000 by age 18 provides a unique opportunity to explore risk factors and underlying mechanisms of atopic disease and other lifestyle-related, non-communicable diseases such as obesity and neuropsychiatric disorders, which are highly prevalent in the community and our cohort.

Abstract 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.

Background: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). Objectives: We investigated associations between urban environment exposures during pregnancy and PPD. Methods: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686–30,716 depending on exposure; representing 26–46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3–18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. Results: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs.

Ethnic disparities in stillbirth exist in Europe and suboptimal care due to miscommunication is one contributing cause. The MAMAACT intervention aimed to reduce ethnic disparity in stillbirth and newborns' health through improved management of pregnancy complications. The intervention encompassed training of antenatal care midwives in cultural competencies and intercultural communication combined with health education materials for the expecting parents about symptoms of pregnancy complications. The evaluation consisted of a qualitative in-depth implementation analysis and a process evaluation embedded in a cluster randomized trial including 19 of 20 maternity wards in Denmark. In this article, the findings from the different evaluation perspectives are integrated. The integration follows the principles of realist evaluation by analyzing to what extent the MAMAACT activities were generating mechanisms of change in interaction with the context. The integration analysis shows that the health education materials in the MAMAACT intervention contributed to heightened health literacy concerning pregnancy complications among pregnant women. Additionally, the training of midwives in cultural competency and intercultural communication raised awareness among midwives. Nonetheless, the exclusive emphasis on midwives and the inflexibility in care provision hindered them from changing their communication practices. To enhance the cultural competence in maternity care, it is essential to implement more comprehensive initiatives involving healthcare professionals in maternity care at all levels, from pregraduate to postgraduate. Adequate interpreter services and management support should also be ensured. Currently, the Danish antenatal care system faces challenges including inadequate information transfer between healthcare sectors, insufficient differentiation of care, and inflexibility in midwife scheduling. This results in a lack of responsiveness to the individual needs of women with immigrant backgrounds, potentially reproducing health inequities.

Objectives Our aim was to investigate the association between early environmental factors and the development of coeliac disease (CeD) in adolescents, recruited from a cohort nested in the Danish National Birth Cohort (DNBC).Design The study was designed as a prospective cohort study, nested in DNBCParticipants The Glutenfunen cohort comprises 1266 participants, nested in DNBC. All participants were screened for CeD, and in total, 28 cases of biopsy proven CeD were identified. Data about breastfeeding, timing of introduction to solid food in infancy, use of antibiotics, infections and symptoms were parentally reported prospectively at 6 months and 18 months, respectively. We estimated ORs and 95% CIs of CeD in adolescents using logistic regression analysis.Results Viral croup reported at 18 months of age was associated with CeD in adolescents with an OR of 3.2 (95% CI: 1.2 to 8.7). Furthermore, otitis media also reported at 18 months of age was linked with CeD with an OR of 3.2 (95% CI: 1.5 to 7.3). We were not able to find any statistical associations between CeD and breastfeeding, frequency of infections, parentally reported use of antibiotic and timing of solid foods.Conclusion In this study, we present an overview of the relationship between early environmental factors and occurrence of CeD in adolescents. Our findings, despite limitations due to a limited number of cases of CeD, suggest a role of viral infections in the pathogenesis of CeD

Abstract Preterm birth is associated with smaller body dimensions at birth. The impact on body size in later life, measured by body mass index (BMI) and height, remains unclear. A prospective register-based cohort study with 62,625 singletons from the Danish National Birth Cohort born 1996–2003 for whom information on gestational age (GA) at birth, length or weight at birth, and at least two growth measurements scheduled at the ages of 5 and 12 months, and 7, 11 and 18 years were available. Linear mixed effects with splines, stratified by sex, and adjusted for confounders were used to estimate standardised BMI and height. GA was positively associated with BMI in infancy, but differences between preterm and term children declined with age. By age 7, preterm children had slightly lower BMI than term children, whereas no difference was observed by adolescence (mean difference in BMI z-score − 0.28 to 0.15). GA was strongly associated with height in infancy, but mean differences between individuals born preterm and term declined during childhood. By adolescence, the most preterm individuals remained shorter than their term peers (mean difference in height z-score from − 1.00 to − 0.28). The lower BMI in preterm infants relative to term infants equalizes during childhood, such that by adolescence there is no clear difference. Height is strongly positively associated with GA in early childhood, whilst by end of adolescence individuals born preterm remain slightly shorter than term peers.

Abstract It remains unclear whether the rate of fetal death has changed during the COVID-19 pandemic. We assessed the impact of COVID-19 mitigation measures on fetal death in Sweden (449,347 births), Denmark (290,857 pregnancies) and Norway (261,057 pregnancies) using robust population-based registry data. We used Cox regression to assess the impact of the implementation of pandemic mitigation measures on March 12th, 2020, on miscarriage (fetal loss before gestational week 22) and stillbirth (fetal loss after gestational week 22). A total of 11% of 551,914 pregnancies in Denmark and Norway ended in miscarriage, while the proportion of stillbirths among 937,174 births across the three countries was 0.3%. There was no difference in the risk of fetal death during the year following pandemic mitigation measures. For miscarriage, the combined hazard ratio (HR) for Norway and Denmark was 1.01 (95% CI 0.98, 1.03), and for stillbirth, the combined HR for all three countries was 0.99 (95% CI 0.89, 1.09). We observed a slightly decreased risk of miscarriage during the first 4 months, with an HR of 0.94 (95% CI 0.90, 0.99) after lockdown. In conclusion, the risk of fetal death did not change after the implementation of COVID-19 pandemic mitigation measures in the three Scandinavian countries.

Objectives To compare the risk of adverse perinatal outcomes according to infants who are born small for gestational age (SGA; 90th centile), as defined by birthweight centiles that are non-customised (ie, standardised by sex and gestational age only) and customised (by sex, gestational age, maternal weight, height, parity, and ethnic group).Design Comparative, population based, record linkage study with meta-analysis of results.Setting Denmark, Finland, Norway, Wales, and England (city of Bradford), 1986-2019.Participants 2 129 782 infants born at term in birth registries.Main outcome measures Stillbirth, neonatal death, infant death, admission to neonatal intensive care unit, and low Apgar score (

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

Abstract The objectives of the current study were to identify risk factors for SARS-CoV-2 positivity, and to address how different testing strategies, choice of comparison group, and population background characteristics may influence observed associations. National registries data for 107,627 pregnant women in Sweden and 81,195 in Norway, were used to identify risk factors for SARS-CoV-2, separately for women under non-universal testing (testing by indication) and universal testing (testing of all pregnant women in contact with a delivery ward). We also investigated underlying characteristics associated with testing for SARS-CoV-2. Overall, 2.1% of pregnant women in Sweden and 1.1% in Norway were test-positive during the pandemic’s first 18 months. We show that the choice of test strategy for SARS-CoV-2 provided different associations with risk factors for the disease; for instance, women who were overweight, obese or had gestational diabetes had increased odds of being test-positive under non-universal testing, but not under universal testing. Nevertheless, a consistent pattern of association between being born in the Middle East and Africa and test-positivity was found independent of test strategy and in both countries. These women were also less likely to get tested. Our results are useful to consider for surveillance and clinical recommendations for pregnant women during the current and future pandemics.

Abstract Many studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87–5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05–0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics.

Abstract We aimed to investigate if declines in youth’s mental health during lockdown were dependent on housing condition among 7445 youth (median age ~ 20 years) from the Danish National Birth Cohort (DNBC), with data collected at 18 years of age and again three weeks into the first national lockdown (April 2020). We examined associations between housing conditions (access to outdoor spaces, urbanicity, household density, and household composition) and changes in mental health (mental well-being, Quality of Life (QoL) and loneliness). We report results from multivariate linear and logistic regression models. Youth without access to outdoor spaces experienced greater declines in mental well-being (vs. garden; mean difference: − 0·75 (95% CI − 1·14, − 0·36)), and correspondingly greater odds of onset of low mental well-being (vs. garden; OR: 1·72 (95% CI 1·20, 2·48)). Youth in higher density households vs. below median or living alone vs. with parents only also had greater odds of onset of low mental well-being (OR: 1·26 (95% CI 1·08, 1·46) and OR: 1·62 (95% CI 1·17, 2·23), respectively). Living in denser households (vs. below median; OR: 1·18 (95% CI 1·06, 1·33), as well as living alone (vs. with parents; OR: 1·38 (95% CI 1·04, 1·82) was associated with onset of low QoL. Living alone more than doubled odds of onset of loneliness compared to living with parents, OR: 2·12 (95% CI 1·59, 2·82). Youth living alone, in denser households, and without direct access to outdoor spaces may be especially vulnerable to mental health declines.

BackgroundPreterm 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 findingsWe 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.ConclusionsThis 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.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Abstract The aim of this study was to examine associations between selected sociodemographic, socioeconomic, and health characteristics and the rates of fatherhood in different age groups. We investigated rates between 2011 and 2015 in a population-based register study including all men born from 1945 to 1995 residing in Denmark in 2011. The study population consisted of 1,867,108 men who fathered 268,612 children during the follow-up. The associations were quantified as incidence rate ratios using Poisson regression. Young men had higher rates of fathering a child if they lived outside the Capital Region, had a relatively high income, were previously diagnosed with cardiovascular disease, psychoactive substance abuse, personality disorders, schizophrenia or behavioural and emotional disorders. Men of advanced age had higher rates of fathering a child when born outside Denmark, living in the Capital Region, were in the lower or upper 10th percentile income group, were self-employed or unemployed or previously diagnosed with depression. Men of advanced age had lower rates of fathering a child if previously diagnosed with somatic diseases, psychoactive substance abuse or mental retardation. The findings highlight the importance of consideration of various sociodemographic, socioeconomic, and health characteristics when studying associations between paternal age and offspring health.

Abstract Background To investigate how screen time and physical activity behavior were associated with spinal pain in pre-adolescence. Methods This study included 45,555 pre-adolescents who participated in the 11-year follow-up of the Danish National Birth Cohort. The 11-year follow-up included self-reported information on computer and TV behavior, aspects of physical activity, as well as frequency and intensity of spinal pain (neck-, mid back- and low back pain). Data were linked with parental socioeconomic data from Statistics Denmark registers. Associations were estimated using multinomial logistic regression models. To account for sample selection, we applied inverse probability weighting. Results Duration of screen time was stepwise associated with the degree of spinal pain. Compared with those spending

Abstract Ethnic disparity in stillbirth and infant death has been demonstrated in Europe. As the relation between migration and health change over time, this population based register study investigated the recent figures and explored if potential differences could be explained by the well-known educational and income inequalities in stillbirth and infant death using a novel approach. Stillbirth and infant mortality varied considerably according to country of origin, with only immigrants from China, Norway, and Poland having an overall lower risk than Danish women. Women of Pakistani, Turkish, and Somali origin had a particularly high risk of both outcomes. Women from recent high conflict areas displayed a pattern with increased stillbirth risk. An observed excess risks across generations was found, which is disturbing and rule out factors related to language barriers or newness. Differences in educational level and household income explained only part of the observed inequalities. Strengthening of the maternity care system to better understand and meet the needs of immigrant women seems needed to mitigate the disparities.

Abstract The objective of the present study was to explore past and future primary health care use in preadolescents reporting frequent non-specific health complaints or a low self-rated health compared to that of preadolescents with no frequent health complaints or with good self-rated health. The study was conducted as a cohort study based within the Danish National Birth Cohort (1996–2002). Information on non-specific health complaints and self-rated health was obtained by an 11-year follow-up questionnaire. Information about number of general practitioner (GP) contacts was obtained from the Health Insurance Service Register. A total of 44,877 pre-adolescents gave complete exposure information. Pre-adolescents who reported frequent non-specific health complaints had a higher use of GP compared to pre-adolescents without complaints across the five years following the index date (somatic complaints: IRR = (1.46 [1.38; 1.55], mental complaints: IRR = 1.16 [1.12; 1.19], both complaints: IRR = 1.58 [1.47; 1.69]). The same pattern was found for the association between low self-rated health and number of GP contacts (IRR = 1.41 (1.36; 1.46)). Non-specific health complaints and a poor self-rated health in pre-adolescents was associated with a higher past and future use of GP, indicating a need for development of early interventions with help for symptom management.

Background: Housing and indoor home environments are associated with the risk of infections and asthma in children. To better understand the determinants and characteristics of these environments, we aimed to describe the associations between parental health and socioeconomic position and housing and indoor home environments of children in Denmark, and the clustering of the factors within these environments. Methods: Offspring in the Danish National Birth Cohort (DNBC) whose parents responded to the 11-year follow-up were eligible for inclusion. We included complete cases only. Data on the indoor and housing environments (i.e. variables on housing, sources of gaseous and particle pollution, mould and moisture, and pets) were collected through an online questionnaire responded to by a parent. Data on socioeconomic position were obtained through linkage with registry data on maternal education at offspring birth and household equivalized income at offspring birth. Data on parental health were obtained by linking self-reported data from the 11-year follow-up for mother and father with administrative registry data for the mother. We present descriptive statistics and exploratory factor analyses. Results: A total of 42 723 offspring were included for analyses. The distributions of nearly all indoor and housing environments differed according to educational and income strata, with patterns similar for both education and income. Generally, higher parental educational and income strata had more favorable indoor and housing environments (less secondhand smoking, gas stove use, mould and condensation and higher house ownership, detached house dwellings and newer building age). However, candle use was approximately similar between strata, fireplace use among lower educational and income strata tended towards the extremes (none or daily), and water damage was more common among higher educational and income strata. Parental health was strongly associated with housing and indoor home environment factors - especially parental affective disorders was strongly associated with mould. Four factors were extracted from the exploratory factor analyses, relating primarily in order of extraction to: housing ownership, mould and moisture, candle use and household density. Conclusion: Parental health and socioeconomic position are strongly related to housing and indoor home environments. Additionally, several factors in these environments correlate strongly and cluster together. Observational studies on associations and causal effects of factors in the indoor and housing environments of children on their morbidity, must consider both of these conclusions to arrive at valid estimates and effects.

Summary: Background: Children born into disadvantaged socioeconomic circumstances are more likely to experience both adversity during childhood and premature mortality. The aim of this study was to investigate how much of the parental education gradient in early adult mortality is explained by exposure to childhood adversity. Methods: We used data from the nationwide register-based Danish Life Course cohort study. Our sample consisted of all individuals born between Jan 1, 1980, and Dec 31, 2001, who did not emigrate or die before age 16 years, and for whom information on parental education level was available. These individuals were followed up for mortality from age 16 years until Dec 31, 2018. Highest attained parental education level at birth was divided into low (≤9 years), medium (10–12 years), and high (>12 years) according to years in education. Individuals were assigned to one of five childhood adversity trajectory groups based on their annual exposure between age 0 and 16 years to a broad selection of adversities in three dimensions: material deprivation, loss or threat of loss in the family, and family dynamics. Childhood abuse was not included. The association between parental education level and mortality was assessed with a Cox proportional hazards model. To assess the magnitude of mediation of this association by childhood adversity, we used counterfactual mediation analysis and an Aalen additive hazards model. Analyses were unadjusted and adjusted for parental origin and parental ages at birth. Findings: Our sample consisted of 1 278 156 individuals followed up from birth until age 16–38 years. The sample comprised 655 633 (51·3%) men and 622 523 (48·7%) women, and 1 243 981 (97·3%) participants were of European descent. During follow-up, 5387 deaths were registered. Compared with the high parental education group, we calculated a total effect equal to 8·7 additional deaths (95% CI 6·6–10·9) per 100 000 person-years in the medium parental education group and 31·9 (28·5 to 35·2) per 100 000 person-years in the low parental education group. Mediation through childhood adversity trajectories accounted for 41·5% (95% CI 8·0–67·5) of the additional deaths in the medium parental education group and 46·4% (32·9–58·8) of the additional deaths in the low parental education group. The results were similar when adjusting the analyses for sociodemographic factors. Interpretation: The experience of childhood adversity seems to be an important mediator of the association between parental education and mortality in early adulthood. Interventions reducing the exposure to childhood adversity might thus reduce the parental education gradient in early adult mortality. Funding: Netherlands Organisation for Health Research and Development.

Background Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking, and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and Results Seven European birth cohorts, including 232 390 offspring (2469 CHD cases [1.1%]), were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking, and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression, adjusting for confounders and the other parent's exposure and combined estimates using a fixed‐effects meta‐analysis. In adjusted analyses, maternal overweight (odds ratio [OR], 1.15 [95% CI, 1.01–1.31]) and obesity (OR, 1.12 [95% CI, 0.93–1.36]), compared with normal weight, were associated with higher odds of CHD, but there was no clear evidence of a linear increase in odds across the whole BMI distribution. Associations of paternal overweight, obesity, and mean BMI were similar to the maternal associations. Maternal pregnancy smoking was associated with higher odds of CHD (OR, 1.11 [95% CI, 0.97–1.25]) but paternal smoking was not (OR, 0.96 [95% CI, 0.85–1.07]). The positive association with maternal smoking appeared to be driven by nonsevere CHD cases (OR, 1.22 [95% CI, 1.04–1.44]). Associations with maternal moderate/heavy pregnancy alcohol consumption were imprecisely estimated (OR, 1.16 [95% CI, 0.52–2.58]) and similar to those for paternal consumption. Conclusions We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for the importance of smoking cessation during pregnancy.

Abstract Background Studies have shown differences in the risk of caesarean section (CS) between ethnic minority groups. This could be a marker of unequal health care. The aim of this study was to investigate differences in the risk of CS between immigrants of various origins in Denmark, where all health care is free and easy to access, and Danish-born women. A further aim was to determine the possible influence of known risk factors for CS. Methods The design was a population-based register study using national Danish registers and included all live- and stillborn singleton deliveries by primiparous women in Denmark from 2004 to 2015. The total study population consisted of 298,086 births, including 25,198 births to women from the 19 largest immigrant groups in Denmark. Multinomial logistic regression analysis was used to estimate relative risk ratios (RRR) of emergency and planned CS, using vaginal delivery (VD) as reference, in immigrant women compared to Danish-born women. A number of known risk factors were included separately. Results Women from Turkey, the Philippines, Thailand, Somalia, Vietnam, Iran and Afghanistan had a statistically significant elevated risk ratio of emergency CS vs. VD compared to Danish-born women; adjusted RRR’s ranging 1.15–2.19. The risk ratio of planned CS vs. VD was lower among the majority of immigrant groups, however higher among women from Poland, Thailand and Iran, when compared to Danish-born women. None of the studied explanatory variables affected the risk ratio of planned CS vs. VD, whereas maternal height contributed with varying strength to the risk ratio of emergency CS vs. VD for all immigrant groups. Conclusion Substantial variations in CS risks by maternal country of birth were documented. Some of the disparities in emergency CS seem to be explained by maternal height.

Psoriasis is associated with cardiometabolic comorbidity; however, whether this is due to common lifestyle-related risk factors is unclear. This study investigated the association between psoriasis and cardiometabolic comorbidity, taking body mass index and smoking into account. The population comprised expectant mothers in the Danish National Birth Cohort (established 1996–2002). During pregnancy, the women were asked about physician-diagnosed psoriasis. Any association with self-reported cardiometabolic comorbidity 11 years later was assessed using logistic regression. The cohort was also followed up for hospital-diagnosed comorbidity, including cardiac death, until 31 December 2014, and the risk was assessed using Cox regression. A total of 2,435 women with psoriasis (2.90%) and 81,388 women without were identified. Psoriasis was significantly associated with self-reported hypercholesterolaemia (adjusted odds ratio 1.31; 1.01–1.70) and hospital-diagnosed hypertension (adjusted hazard ratio 1.33; 1.08–1.65). Women with psoriasis have an increased risk of developing cardiometabolic comorbidity in early adult life.

Objectives We assessed social inequalities in child mental health problems (MHPs) and how they are mediated by perinatal factors, childhood illness and maternal mental health in two national birth cohorts.Design Longitudinal cohort studySetting We used data from the UK Millennium Cohort Study and the Danish National Birth Cohort.Primary and secondary outcome measures We applied causal mediation analysis to longitudinal cohort data. Socioeconomic conditions (SECs) at birth were measured by maternal education. Our outcome was child MHPs measured by the Strength and Difficulty Questionnaire at age 11. We estimated natural direct, indirect and total effects (TEs) of SECs on MHPs. We calculated the proportion mediated (PM) via three blocks of mediators—perinatal factors (smoking/alcohol use during pregnancy, birth weight and gestational age), childhood illness and maternal mental health.Results At age 11 years, 9% of children in the UK and 3.8% in Denmark had MHPs. Compared with high SECs, children in low SECs had a higher risk of MHPs (relative risk (RR)=4.3, 95% CI 3.3 to 5.5 in the UK, n=13 112; and RR=6.2, 95% CI 4.9 to 7.8 in Denmark, n=35 764). In the UK, perinatal factors mediated 10.2% (95% CI 4.5 to 15.9) of the TE, and adding maternal mental health tripled the PM to 32.2% (95% CI 25.4 to 39.1). In Denmark, perinatal factors mediated 16.5% (95% CI 11.9 to 21.1) of the TE, and including maternal mental health increased the PM to 16.9% (95% CI 11.2 to 22.6). Adding childhood illness made little difference in either country.Conclusion Social inequalities in child mental health are partially explained by perinatal factors in the UK and Denmark. Maternal mental health partially explained inequalities in the UK but not in Denmark.

BackgroundFetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight.Methods and findingsWe performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations.ConclusionsWe observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Abstract Background Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. Methods We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. Results We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4–17.4) for underweight women, 14.5 kg (11.5–17.7) for normal weight women, 13.9 kg (10.1–17.9) for overweight women, and 11.2 kg (7.0–15.7), 8.7 kg (4.3–13.4) and 6.3 kg (1.9–11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. Conclusions Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

OBJECTIVES: Exposure to traffic noise and air pollution is suspected to increase susceptibility to viral infections – the main triggering factor for febrile seizures. No studies have examined these two exposures in relation to febrile seizures. We aimed to investigate whether exposure to road traffic noise and air pollution are associated with risk of febrile seizures in childhood. METHODS: From our study base of 51 465 singletons from a national birth cohort, we identified 2175 cases with febrile seizures using a nationwide registry. Residential address history from conception to six years of age were found in national registers, and road traffic noise (L_den) and air pollution (NO_2) were modeled for all addresses. Analyses were done using Cox proportional hazard model with adjustment for potential confounders, including mutual exposure adjustment. RESULTS: An interquartile range (IQR) increase in childhood exposure to road traffic noise and air pollution was associated with an 11% [incidence rate ratio (IRR) 1.11, 95% confidence interval (CI) 1.04–1.19) and 5% (IRR 1.05, 95% CI 1.02–1.07) higher risk for febrile seizures, respectively, after adjustment for potential confounders. Weaker tendencies were seen for pregnancy exposure. In models with mutual exposure adjustment, the estimates were slightly lower, with IRR of 1.08 (95% CI 1.00–1.16) and 1.03 (95% CI 0.99–1.06) per IQR increase in childhood exposure to road traffic noise and air pollution, respectively. CONCLUSIONS: This study suggests that residential exposure to road traffic noise and air pollution is associated with higher risk for febrile seizures.

We aimed to identify sociodemographic predictors of compliance after receiving a personalised reminder on lacking vaccinations against MMR (Measles, Mumps, Rubella) and/or HPV (Human Papilloma Virus) among parents of Danish adolescent girls.A nationwide register-based study, including all 14-year-old girls (15 May 2014–14 May 2015) lacking either MMR, HPV-vaccination or both. Vaccination-compliance following a postal reminder was modelled using multivariable logistic regression and included the following socio-demographic predictors: maternal age, education, employment and ethnicity. Birth order, number of siblings, family-structure, location of residence, and household income.The parents of 9692 girls received a reminder. Out of 4940 exclusively lacking an HPV-vaccine, 15.3% were subsequently vaccinated. Among 2026 only lacking an MMR vaccination, 8.5% were vaccinated. Among 2726 girls lacking both, 5% received an HPV, 4.4% an MMR and 5.4% received both vaccinations. We identified sociodemographic differences between reminderletter-compliers and non-compliers, also according to vaccination types. Non-western descendants were more likely to receive HPV-vaccination, although the association was only significant for those who only lacked HPV (OR 2.02, 95% 1.57–2.59). For girls only lacking an MMR, regional differences were identified. Among girls lacking both vaccines, girls of mothers with intermediate (OR 0.63, 0.42–0.95) or basic education (OR 0.43, 0.24–0.75) were less likely to be vaccinated compared to girls of higher educated mothers.Reminders were in particular effective in increasing HPV uptake among immigrants of non-Western ethnicity. We found reminders to be less effective among less educated mothers whose daughters lacked both vaccines. To increase the coverage in this group, additional interventions are needed. Keywords: Vaccination, Immunization, Socioeconomic factors

Abstract Background Cerebral palsy is the most frequent motor disability in childhood, but little is known about its etiology. It has been suggested that cerebral palsy risk may be increased by prenatal thyroid hormone disturbances. The objective of this study was to investigate whether maternal thyroid disorder is associated with increased risk of cerebral palsy. Methods A population-based cohort study using two study populations. 1) 1,270,079 children born in Denmark 1979–2007 identified in nationwide registers, and 2) 192,918 children born 1996–2009 recruited into the Danish National Birth Cohort and The Norwegian Mother and Child Cohort study, combined in the MOthers and BAbies in Norway and Denmark (MOBAND) collaboration cohort. Register-based and self-reported information on maternal thyroid disorder was studied in relation to risk of cerebral palsy and its unilateral and bilateral spastic subtypes using multiple logistic regression. Children were followed from the age of 1 year to the age of 6 years, and cerebral palsy was identified in nationwide registers with verified diagnoses. Results In register data, hypothyroidism was recognized in 12,929 (1.0%), hyperthyroidism in 9943 (0.8%), and unclassifiable thyroid disorder in 753 (

Psoriasis is an immune-mediated inflammatory disease, which, in studies among adults, have been shown to cluster with autoimmune disease. The aim of this cross-sectional register study was to examine possible associations between 9 pre-selected autoimmune diseases and psoriasis in children and adolescents. The study population consisted of all individuals living in Denmark, age under 18 years on 31 December 2012. A total of 1,925 children and adolescents with psoriasis and 1,194,712 without psoriasis were identified. Psoriatic arthritis (adjusted odds ratio (OR) 10.08; 7.97–12.74), rheumatoid arthritis (adjusted OR 6.61; 2.75–15.87) and vitiligo (adjusted OR 4.76; 1.71–13.20) showed strong associations with psoriasis. In addition to increased risk of selected autoimmune diseases, the presence of psoriasis was associated with increased risk of multiple concurrent autoimmune diseases compared with children and adolescents with­out psoriasis. Clinicians should be aware of extracutaneous symptoms when treating children and adole­scents with psoriasis.

BackgroundMaternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.Methods and findingsWe conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.ConclusionsIn this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

BACKGROUND:Previous studies have investigated physical and psychosocial job exposures separately in relation to foetal growth. We therefore investigated if occupational lifting and psychosocial job strain interact to affect foetal growth and gestational length. We hypothesised that heavy lifting and high job strain would increase the risk of impacted foetal growth (small or large for gestational age) and preterm birth. METHODS:The cohort included 47,582 pregnancies from the Danish National Birth Cohort (1996-2002), where the woman was pregnant at 22 gestational weeks (GW), expected one child and worked ≥30 hours/week. Information on occupational lifting and psychosocial job strain was derived from an interview (16±3.0 GW). Data to calculate small and large for gestational age (SGA/LGA) and gestational length was retrieved from the Medical Birth Register. Interaction between lifting and job strain (Karasek's model) was analysed by multinomial logistic regression. RESULTS:Overall, the adjusted regression analysis showed statistically significant interaction between lifting and job strain for SGA and LGA. For each additional 250 kg lifted/day, high strain women (high Demand/low Control) had increased odds of giving birth to a LGA-child (OR = 1.15; 95% CI 1.06-1.26), whereas women in the active group (high Demand/high Control) had increased odds of giving birth to a SGA child (OR = 1.12; 95% CI 1.03-1.23). When women lifting ≤1000 kg/day were excluded in the sensitivity analyses the interaction between lifting and job strain became insignificant. No interaction of lifting and job strain was found for gestational length. CONCLUSIONS:The main findings may give some support to our hypothesis, as lifting in combination high with job strain increased the risk of giving birth to a LGA child. This finding was, however, not supported in the sensitivity analysis and no association of the interaction was found relative to gestational length.

OBJECTIVES: We assessed whether maternal employment during pregnancy – overall and in selected occupational sectors – is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. METHODS: We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. RESULTS: Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (OR_adj) 0.86, 95% confidence interval (95% CI) 0.81–0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (OR_adj 0.91, 95% CI 0.84–0.99) whereas food industry workers had an increased risk of preterm delivery (OR_adj 1.50, 95% CI 1.12–2.02). There was little evidence for heterogeneity between cohorts. CONCLUSIONS: This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development.

Background: The aim of this study was to determine antibody titres against Campylobacter, Salmonella, and Yersinia in a population-based cohort of pregnant women in Denmark in order to evaluate adverse pregnancy outcomes (miscarriage, preterm birth, and small for gestational age) in relation to occupational exposure to animals in women exposed to food producing animals. Methods: We used data and blood samples from the Danish National Birth Cohort. Serum samples collected during the first trimester from 192 pregnant women who were occupationally exposed to domestic animals and 188 randomly selected unexposed pregnant women were analysed for IgG, IgM, and IgA antibodies against Campylobacter, Salmonella, and Yersinia. Pregnancy outcomes of interest were identified through the Danish National Patient Register. Results: Women with occupational exposure to animals had significantly higher IgG antibody concentrations against Campylobacter, Salmonella, and Yersinia, whereas they had lower concentrations of IgM and IgA antibodies. Conclusions: Serological markers were not identified as risk factors for adverse pregnancy outcomes, with the exception of elevated concentrations of Salmonella antibodies, which were found to be associated with an increased risk of preterm birth.

OBJECTIVES: It has been suggested that the handling of heavy loads during pregnancy is associated with impaired fetal growth. We examined the association between quantity and frequency of maternal occupational lifting and the child’s size at birth, measured by weight, length, ponderal index, small-for-gestational-age (SGA), abdominal circumference, head circumference, and placental weight. METHODS: We analyzed birth size from the Danish Medical Birth Registry of 66 693 live-born children in the Danish National Birth Cohort according to the mother’s self-reported information on occupational lifting from telephone interviews around gestational week 16. Data were collected in the period 1996–2002. We used linear and logistic regression models and adjusted for confounders. RESULTS: In the fully adjusted models, most of the mean differences in birth size measures had values indicating a smaller size of offspring among women with occupational lifting versus women with no lifting, but the differences were very small, and there was a statistically significant trend only for placental weight showing lighter weight with increasing number of kilos lifted per day. In jobs likely to include person-lifting, we found increased odds of SGA among children of women who lifted 501–1000 kilos per day [odds ratio (OR) 1.34, 95% confidence interval (95% CI) 0.98–1.83] and >1000 kilos per day (OR 1.51, 95% CI 0.83–2.76) compared to no lifting. In jobs with no person-lifting, occupational lifting was not associated with SGA. CONCLUSIONS: Overall, we observed no strong support for an association between maternal occupational lifting and impaired size at birth. Our data indicated a potential association between lifting and SGA among offspring of women in occupations that are likely to include person-lifting. These results should, however, be interpreted with caution due to limited statistical power, and we suggest that future studies include detailed, individual information on job functions and ergonomic routines of lifting procedures.

OBJECTIVE: The aim of the present study was to examine the association between occupational lifting and the risk of fetal death according to gestational age. METHODS: We used data from the Danish National Birth Cohort (1996–2002). Among 71 500 occupationally active women, 2886 experienced a fetal death. Information on lifting and relevant covariates was collected in interviews around week 16 of pregnancy. The majority of fetal losses (N=2032) happened before the scheduled interview, and exposure data were collected retrospectively from these women. We analyzed early miscarriage (≤12 weeks), late miscarriage (13–21 weeks), and stillbirth (≥22 weeks), using Cox-regression models with gestational age as the underlying time variable. RESULTS: The adjusted early miscarriage risk increased with frequency of daily lifts and total burden lifted per day. For example, the hazard ratio was 1.38 [95% confidence interval (95% CI) 1.10–1.74] for a total weight load per day of 101–200 kg and 2.02 (95% CI 1.23–3.33) for a daily load >1000 kg as compared to non-lifters (P for trend

OBJECTIVES: Pelvic pain during pregnancy is a common ailment, and the disease is a major cause of sickness absence during pregnancy. It is plausible that occupational lifting may be a risk factor of pelvic pain during pregnancy, but no previous studies have examined this specific exposure. The aim of this study was to examine the association between occupational lifting and pelvic pain during pregnancy. METHODS: The study comprised 50 143 pregnant women, enrolled in the Danish National Birth Cohort in the period from 1996–2002. During pregnancy, the women provided information on occupational lifting (weight load and daily frequency), and six months post partum on pelvic pain. Adjusted odds ratios for pelvic pain during pregnancy according to occupational lifting were calculated by logistic regression. RESULTS: Any self-reported occupational lifting (>1 time/day and loads weighing >10 kg) was associated with an increased risk of pelvic pain during pregnancy as compared to no such lifting. A confounder-adjusted exposure-response relation was observed between self-reported total loads lifted and pelvic pain during pregnancy. Daily lifting of both medium (11–20 kg) and heavy loads (>20 kg) were associated with increased risk, and the highest risk was observed among women who lifted heavy loads independent of exposure to medium loads. CONCLUSION: Occupational lifting may increase the risk of pelvic pain during pregnancy.

AIM:To explore antidiabetic medicine prescribing to women before, during and after pregnancy in different regions of Europe. METHODS:A common protocol was implemented across seven databases in Denmark, Norway, The Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. Women with a pregnancy starting and ending between 2004 and 2010, (Denmark, 2004-2009; Norway, 2005-2010; Emilia Romagna, 2008-2010), which ended in a live or stillbirth, were identified. Prescriptions for antidiabetic medicines issued (UK) or dispensed (non-UK) during pregnancy and/or the year before or year after pregnancy were identified. Prescribing patterns were compared across databases and over calendar time. RESULTS:1,082,673 live/stillbirths were identified. Pregestational insulin prescribing during the year before pregnancy ranged from 0.27% (CI95 0.25-0.30) in Tuscany to 0.45% (CI95 0.43-0.47) in Norway, and increased between 2004 and 2009 in all countries. During pregnancy, insulin prescribing peaked during the third trimester and increased over time; third trimester prescribing was highest in Tuscany (2.2%) and lowest in Denmark (0.5%). Of those prescribed an insulin during pregnancy, between 50.5% in Denmark and 88.8% in the Netherlands received an insulin analogue alone or in combination with human insulin, this proportion increasing over time. Oral products were mainly metformin and prescribing was highest in the 3 months before pregnancy. Metformin use during pregnancy increased in some countries. CONCLUSION:Pregestational diabetes is increasing in many areas of Europe. There is considerable variation between and within countries in the choice of medication for treating pregestational diabetes in pregnancy, including choice of insulin analogues and oral antidiabetics, and very large variation in the treatment of gestational diabetes despite international guidelines.

BackgroundAfter the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world.AimTo examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again.MethodsTHE TRENDS IN THE PREVALENCE RATES WERE BASED ON THREE DATA SETS PROVIDING COMPARABLE REPEATED ESTIMATES: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI).ResultsThe prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI's from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed.ConclusionThis study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.

Background and aimsQ fever is a bacterial zoonosis caused by infection with Coxiella burnetii. It is well established that Q fever causes fetal loss in small ruminants. The suspicion has been raised that pregnant women may also experience adverse pregnancy outcome when the infection is acquired or reactivated during pregnancy. The purpose of this study was to assess the potential association between serologic markers of infection with C. burnetii and spontaneous abortion.MethodsA nested case-control study within the Danish National Birth Cohort, a cohort of 100,418 pregnancies recruited from 1996-2002. Women were recruited in first trimester of pregnancy and followed prospectively. Median gestational age at enrolment was 8 weeks (25 and 75 percentiles: 7 weeks; 10 weeks). During pregnancy, a blood sample was collected at gestational week 6-12 and stored in a bio bank. For this study, a case sample of 218 pregnancies was drawn randomly among the pregnancies in the cohort which ended with a miscarriage before 22 gestational weeks, and a reference group of 482 pregnancies was selected in a random fashion among all pregnancies in the cohort. From these pregnancies, serum samples were screened for antibodies against C. burnetii in a commercial enzyme-linked immunosorbent assay (ELISA). Samples that proved IgG or IgM antibody positive were subsequently confirmatory tested by an immunofluorescence (IFA) test.ResultsAmong cases, 11 (5%) were C. burnetii positive in ELISA of which one was confirmed in the IFA assay compared to 29 (6%) ELISA positive and 3 IFA confirmed in the random sample.ConclusionsWe found no evidence of a higher prevalence of C. burnetii antibodies in serum samples from women who later miscarried and the present study does not indicate a major association between Q fever infection and spontaneous abortion in humans. Very early first trimester abortions were, however, not included in the study.

BackgroundMedications may be consumed periconceptionally before a woman knows she is pregnant. In this study, the authors evaluate the association of a prescription diet drug (Letigen) containing ephedrine (20 mg) and caffeine (200 mg) with spontaneous abortion (SAB) in the Danish National Birth Cohort.MethodsWomen were recruited during their first prenatal visit from 1996-2002. Pre-conception and early pregnancy medication use was reported on the enrollment form, and pregnancy outcome was determined by linking the mother's Civil Registration Number to the Medical Birth Registry and the National Hospital Discharge Register. Of 97,903 eligible pregnancies, 4,443 ended in SAB between 5 and 20 completed gestational weeks, inclusive. Letigen use was reported for 565 pregnancies. Cox regression models accounting for left truncation were fit to estimate the effect of pre-conception and early pregnancy Letigen use on SAB.Principal findingsThe estimated maternal age-adjusted hazard ratio for SAB was 1.1 (95% confidence interval 0.8-1.6) for any periconceptional Letigen use compared to no periconceptional use.ConclusionsAlthough Letigen has high levels of caffeine (the recommended 3 pills/day are approximately equivalent to caffeine from 6 cups of coffee), periconceptional use does not appear to be associated with an appreciably increased hazard of clinically recognized SAB.

BACKGROUND: The Strength and Difficulties Questionnaire (SDQ) is a brief behavioural five factor instrument developed to assess emotional and behavioural problems in children and adolescents. The aim of the current study was to evaluate the psychometric properties for parent and teacher ratings in the Danish version of SDQ for different age groups of boys and girls. METHODS: The Danish versions of the SDQ were distributed to a total of 71,840 parent and teacher raters of 5-, 7- and 10- to 12-year-old children included in four large scale Danish cohorts. The internal reliability was assessed and exploratory factor analyses were carried out to replicate the originally proposed five factor structure. Mean scores and percentiles were examined in order to differentiate between low, medium and high levels of emotional and behavioural difficulties. RESULTS: The original five factor structure could be substantially confirmed. The Conduct items however did not solely load on the proposed Conduct scale and the Conduct scale was further contaminated by non-conduct items. Positively worded items tended to load on the Prosocial scale. This was more so the case for teachers than for parents. Parent and teacher means and percentiles were found to be lower compared to British figures but similar to or only slightly lower than those found in the other Nordic countries. The percentiles for girls were generally lower than for boys, markedly so for the teacher hyperactivity ratings. CONCLUSIONS: The study supports the usefulness of the SDQ as a screening tool for boys and girls across age groups and raters in the general Danish population.