BACKGROUND:Based on experimental and human studies, endocrine disrupting chemicals (EDCs) can disrupt the thyroid hormone system. However, their association with thyroid function tests when considered as part of a chemical mixture is unknown. METHODS:We used data of 1970 pregnant women from the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study to investigate the cross-sectional association between exposure to 26 chemical compounds with maternal thyroid function tests in early pregnancy, using Weighted Quantile Sum (WQS) regression. RESULTS:Higher exposure to EDCs mixtures was associated with a lower FT3 [WQS Estimate per an IQR increase (95 % CI): -0.09 (-0.16 to -0.01), mostly driven by PCBs] and a lower TT3 [WQS Estimate per an IQR increase (95 % CI): -0.05 (-0.09 to -0.01), mostly driven by PFOS]. In addition, higher exposure to a mixture of short lived urinary based compounds was associated with a lower TT4/TT3 ratio while higher exposure to a mixture of persistent serum based compounds was associated with a higher TT4/TT3 ratio. CONCLUSIONS:In this proof-of-principle analysis, we show that there could be an added benefit of analyzing thyroid hormone system disrupting EDCs using a mixture-based analysis approach. Our findings pave the way and provide hypotheses for future experimental and human studies to investigate the effects of EDCs as a mixture on the thyroid hormone system, revealing information on potential biological mechanisms explaining the associations from observational data.

Background Childhood gender nonconformity is related to psychological distress and behavioral difficulties. Similarly, there is evidence for a link between gender nonconformity, or gender dysphoria in some studies, and autism spectrum disorder and related traits. Our knowledge on those associations mostly originates from clinical populations, which might lead to overestimation. Thus, this study aimed to assess associations between gender nonconformity and behavioral difficulties in a population-based study. Methods In the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study, cross-sectional associations between gender-specific play behavior and behavioral outcomes and autistic traits were investigated among 718 children at 7-years of age. Play behavior was measured using the Preschool Activities Inventory; behavioral outcomes and autistic traits were measured with the Strengths and Difficulties Questionnaire and the Social Responsiveness Scale, respectively. Linear and logistic regression analyses were performed. Results Higher composite play behavior scores (indicating either increased masculine or decreased feminine play behavior) were associated with increased autistic trait scores in girls (β = 0.13; 95% confidence interval [CI] = 0.00, 0.26). Furthermore, higher composite scores were shown to be associated with behavioral difficulties in both girls (β = 0.11; 95% CI = 0.04, 0.18) and boys (β = 0.10; 95% CI = 0.02, 0.19). Additionally, higher feminine scores were related with increased problems in peer relationships in boys (β = 0.04; 95% CI = 0.00, 0.07). Conclusions This study suggests a link between gender nonconforming play behavior and autistic traits as well as behavioral difficulties among children in a non-clinical population, which calls attention to the necessity of supporting children with gender nonconformity from early ages.

BackgroundEndocrine disrupting chemicals (EDCs) can cross the placenta and thereby expose the fetus, which may lead to developmental consequences. It is still unclear which chemicals are of concern regarding neurodevelopment and specifically behaviour, when being exposed to a mixture.ObjectiveThe objective is to determine associations between prenatal exposure to EDCs and behavioural difficulties. Furthermore, we investigated sex-specific associations and determined chemicals of concern in significant regressions.MethodsAssociations between prenatal exposure to EDCs (both as single compounds and their mixtures) and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ) were estimated in 607 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study. Levels for chemical compounds were measured in either urine or serum (median of 10 weeks of gestation). Associations were estimated for the total SDQ score (quasipoisson regression) and a 90th percentile cut-off (logistic regression). Exposure for EDC mixtures (phenols, phthalates, PFAS and persistent chlorinated) was studied using weighted quantile sum (WQS) regression with deciles and with and without repeated holdout validation techniques. The models were adjusted for selected covariates.ResultsThe odds for behavioural difficulties increased in girls with higher chemical exposures (OR 1.77, 95% CI 1.67, 1.87) using the full sample and borderline for the validation set (OR 1.31, 95% CI 0.93, 1.85) with 94/100 positive betas in the 100 repeated holdout validations. Chemicals of concern for girls are mostly short-lived chemicals and more specifically plasticizers. No pattern of significant associations was detected for boys.SignificanceThere is an indication of increased behavioural difficulties for girls in the SELMA population with higher exposure to mixtures of EDCs. Using the repeated holdout validation techniques, the inference is more stable, reproducible and generalisable. Prenatal exposure to mixtures of environmental chemicals should be considered when assessing the safety of chemicals.ImpactGrowing evidence points towards a "mixture effect" where different environmental chemicals might act jointly where individual compounds may be below a level of concern, but the combination may have an effect on human health. We are constantly exposed to a complicated mixture pattern that is individual for every person as this mixture depends on personal choices of lifestyle, diet and housing to name a few. Our study suggests that prenatal exposure to EDCs might adversely affect the behaviour of children and especially girls. Hence, risk assessment needs to improve and sex-specific mechanisms should be included in assessments.

Background: A growing body of evidence shows that prenatal exposure to phthalates affects child development. Since many phthalates have been shown to alter endocrine signaling, they may influence reproductive devel-opment, neurodevelopment, and child behavior. Indeed, a few studies reported associations between prenatal phthalate exposure and gender-specific play behavior. However, evidence for this relationship is limited, and previous findings are based on single phthalates, while human exposure entails mixtures of chemicals.Objective: We aimed to investigate the associations between prenatal exposure to single phthalates, as well as a phthalate mixture, and gender-specific play behavior.Methods: A total of 715 mother-child pairs from the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study were included. In the median week 10 of pregnancy, phthalate metabolites were measured in urine. Gender-specific play behavior was measured with Preschool Activities Inventory at the age of seven years. Linear and weighted quantile sum regressions were used; data was stratified by sex. Models were adjusted for child and maternal age, maternal education, parental attitudes toward play behavior, and urinary creatinine concentration. Results: For boys, single compound analyses revealed negative associations of prenatal exposure to di-isononyl phthalate (DINP) concentrations with masculine (13 =-1.44; 95% CI =-2.72,-0.16) and composite (13 =-1.43; 95% CI =-2.72,-0.13) scores. Suggestive associations were also observed with a mixture approach identifying DINP as the main contributor of the association of decreased masculine play. Among girls, higher urinary concentrations of 2,4-methyl-7-oxyooctyl-oxycarbonyl-cyclohexane carboxylic acid (MOiNCH) was associated with decreased feminine (13 =-1.59; 95% CI =-2.62,-0.57) and masculine scores (13 =-1.22; 95% CI =-2.14,-0.29), whereas the mixture analyses did not yield conclusive results for girls. Conclusion: Our findings suggest associations of prenatal exposure to DINP with decreased masculine play behavior in boys while the results for girls were not fully conclusive.

BACKGROUND:International migration has increased during the past years and little is known about the mortality of young adult immigrants and refugees that came to Sweden as children. This study aimed to investigate 1) the risk of all-cause and cause-specific mortality in young accompanied and unaccompanied refugees and non-refugee immigrants compared to Swedish born individuals; and 2) to determine the role of educational level and migrations-related factors in these associations.METHODS:This register linkage study is based on 682,358 individuals (633,167 Swedish-born, 2,163 unaccompanied and 25,658 accompanied refugees and 21,370 non-refugee immigrants) 19-25 years old, who resided in Sweden 31.12.2004. Outcomes were all-cause mortality and mortality due to suicide and external causes. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models with a maximum follow-up to 2016.RESULTS:After adjusting for covariates, all-cause mortality was significantly lower in non-refugee immigrants (aHR 0.70, 95% CI 0.59-0.84) and refugees (aHR 0.76, 95% CI 0.65-0.88) compared to Swedish-born individuals. The same direction of association was observed for mortality due to suicide and external causes. No differences between accompanied and unaccompanied refugees were found. Risk estimates for all migrant groups varied with educational level, duration of residency, age at arrival and country of birth. Further, the mortality risk of migrants arriving in Sweden before the age of 6 years did not significantly differ from the risk of their Swedish-born peers. Low education was a considerable risk factor.CONCLUSION:In general, young adult refugees and non-refugee immigrants have a lower risk of all-cause and cause-specific mortality than Swedish-born individuals. The identified migrant groups with higher mortality risk need specific attention.

Background and aim: Endocrine disrupting chemicals (EDCs) can interfere with the hormone action and are able to cross the placenta and thereby expose the foetus. If the foetus is exposed, it can have an effect on the development of the nervous system with neurobehavioral consequences. Thus, the aim of this study is to estimate the association between prenatal exposure to EDCs and neurobehaviour in children. Methods: Based on the pregnancy cohort Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study, 700 mother-child pairs were selected to estimate associations between prenatal exposure to EDCs and neurobehavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ). Associations were estimated for the total SDQ score and a 90th percentile cut-off to identify cases that might be of clinical importance. Linear, logistic and weighted quantile sum (WQS) regressions were used to estimate betas (β), odds ratios (ORs) and 95% confidence intervals (95% CI). The models were adjusted for urinary creatinine concentration, mother's education, smoking status, age and parity and child's sex and age at outcome assessment. Results: Prenatal levels of MBzP (methylbenzylphthalate) measured in the pregnant mothers' urine were found to be associated with significantly higher SDQ scores (more problems) in adjusted analyses: linear regressions (β 1.49, 95% CI 0.64-2.33) and logistic regression (OR 1.95, 95% CI 1.03-3.70). Further, MBzP was the chemical with the highest weight in the adjusted mixture analyses (WQS), in both the linear (β 0.49, 95% CI 0.22-0.75) and logistic regression (ORs 1.35, 95% CI 1.10-1.64). There were no sex differences in any of the analyses. Conclusions: MBzP, a phthalate used in vinyl flooring and adhesives, seems to be a chemical of concern when assessing indicators for neurobehavioural outcomes in children. Further studies are needed to explain a possible biological mechanism behind these findings. Keywords: Endocrine disrupting chemicals, neurobehaviour

Background As the population is ageing, the need for informal caregivers increases, and thus we need to know more about the effects on caregivers. This study aims to determine both cross-sectional and longitudinal associations between perceived limitation of informal caregiving and mental health of caregivers. Methods This population-based cohort study was based on the Swedish Psykisk hälsa, Arbete och RelaTioner (PART) study, and 9346 individuals aged 18–65 were included. Data were collected through questionnaires, interviews and Swedish registers. Informal care was defined as care given to a family member. Self-reported and diagnosed depression and anxiety were included as outcomes. Covariates included sex, age, social support and socio-economic position. Ordinal logistic regression and Cox regression were performed to determine the associations between caregiving and anxiety or depression. Results Self-reported depression and anxiety was only increased among those experiencing limitations (adjusted odds ratios [aOR] 2.00, 95% confidence intervals [CI] 1.63–2.47 for depression; aOR 2.07, 95% CI 1.57–2.74 for anxiety) compared to those not giving care, respectively. The adjusted hazard ratio (aHR) were increased for diagnosed depression (aHR 1.97, 95% CI 1.27–3.05) and for diagnosed anxiety (aHR 1.86, 95% CI 1.06–3.25) among those giving care and experiencing limitations, compared to those not giving care. No significant associations were found in caregivers without limitations. Conclusion Caregivers experiencing limitations showed a significant association with short- and long-term anxiety and depression. This study implies the importance of exploring the degree to which informal caregiving can be provided without adding burden to caregivers.

Importance Atopic dermatitis is associated with substantial morbidity in childhood. Further understanding of the underlying factors contributing to its onset is needed. Objective To assess the association of exposure to antibiotics in the prenatal period and early childhood with risk of atopic dermatitis in a nationwide population in Sweden. Design, Setting, and Participants This Swedish nationwide, register-based, prospective cohort study used data on mother-child pairs from the Swedish Medical Birth Register linked to other national registers for information on health, socioeconomic, and demographic data. Participants were followed up until an atopic dermatitis outcome, emigration, death, or the end of the study on December 31, 2015. Data for all singleton children and discordant siblings born between March 1, 2006, and December 31, 2010, were included. Data were analyzed from June 1, 2020, to October 31, 2020. Exposures Maternal exposure to systemic antibiotics during pregnancy as well as the child's exposure to systemic antibiotics during the first year of life, as defined by a dispensed prescription in the Swedish Prescribed Drug Register. Main Outcomes and Measures Time-to-event analyses were used to estimate the risk of outcome using attained age as a time scale. Atopic dermatitis was defined based on diagnoses in the National Patient Register and medication listed in the Swedish Prescribed Drug Register. Sibling-control analysis was performed to account for shared familial factors. Results Among the 722 767 singleton children, the mean (SD) age was 5.8 (2.4) years and 351 589 (48.6%) were female. During the follow-up period, 153 407 children (21.2%) were exposed to antibiotics in utero and 172 405 children (23.8%) were exposed during the first year of life. The risk of atopic dermatitis among children exposed to prenatal antibiotics was greater than that among children who were not exposed (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.09-1.12). In the sibling-control analysis, no association was observed (aHR, 0.96; 95% CI; 0.92-1.00). Exposure to antibiotics during the first year of life was associated with a greater risk of atopic dermatitis (aHR, 1.52; 95% CI, 1.50-1.55), with attenuated associations in the sibling-control analysis (aHR, 1.24; 95% CI, 1.20-1.29). Conclusions and Relevance In this cohort study, exposure to antibiotics in early life was associated with an increased risk of atopic dermatitis in the general Swedish population, but this risk was partially confounded by familial factors. Research on the ways in which antibiotic use and other shared familial factors affect other atopic diseases may be warranted.