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OBJECTIVE: To assess the association between maternal asthma and adverse perinatal outcomes in an Australian Indigenous population. METHODS: This prospective cohort study included all Indigenous mother and baby dyads for births from 2001 to 2013 in Western Australia (n = 25 484). Data were linked from Western Australia Births, Deaths, Midwives, Hospital, and Emergency Department collections. Maternal asthma was defined as a self-reported diagnosis at an antenatal visit or hospitalization or emergency visit for asthma during pregnancy or less than 3 years before pregnancy. Associations with birth, labor, and pregnancy outcomes were assessed using generalized estimating equations. Asthma exacerbation during pregnancy and stratification by remoteness was also assessed. RESULTS: Maternal asthma was associated with placental abruption (adjusted odds ratio [aOR], 1.59 [95% confidence interval (CI), 1.07-2.35]), threatened preterm labor (aOR, 1.58 [95% CI, 1.39-1.79]), and emergency cesarean sections (aOR, 1.27 [95% CI, 1.13-1.44]). These risks increased further with an asthma exacerbation during pregnancy or if the mother was from a remote area. No associations were found for low birth weight, preterm birth, small for gestational age, or perinatal mortality. CONCLUSION: Maternal asthma in Indigenous women is associated with an increased risk of emergency cesarean sections, placental abruption, and threatened preterm labor. These risks may be mitigated by improved management of asthma exacerbations during pregnancy.

Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma.

OBJECTIVE: To assess the association between maternal asthma and adverse perinatal outcomes in an Australian Indigenous population. METHODS: This prospective cohort study included all Indigenous mother and baby dyads for births from 2001 to 2013 in Western Australia (n = 25 484). Data were linked from Western Australia Births, Deaths, Midwives, Hospital, and Emergency Department collections. Maternal asthma was defined as a self-reported diagnosis at an antenatal visit or hospitalization or emergency visit for asthma during pregnancy or less than 3 years before pregnancy. Associations with birth, labor, and pregnancy outcomes were assessed using generalized estimating equations. Asthma exacerbation during pregnancy and stratification by remoteness was also assessed. RESULTS: Maternal asthma was associated with placental abruption (adjusted odds ratio [aOR], 1.59 [95% confidence interval (CI), 1.07-2.35]), threatened preterm labor (aOR, 1.58 [95% CI, 1.39-1.79]), and emergency cesarean sections (aOR, 1.27 [95% CI, 1.13-1.44]). These risks increased further with an asthma exacerbation during pregnancy or if the mother was from a remote area. No associations were found for low birth weight, preterm birth, small for gestational age, or perinatal mortality. CONCLUSION: Maternal asthma in Indigenous women is associated with an increased risk of emergency cesarean sections, placental abruption, and threatened preterm labor. These risks may be mitigated by improved management of asthma exacerbations during pregnancy.

Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.

BACKGROUND: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design. METHODS: We conducted a cohort study in twins (7-12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden. RESULTS: Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively). CONCLUSIONS: Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics.

Background Suicide rates are higher in rural Australia than in major cities, although the factors contributing to this are not well understood. This study highlights trends in suicide and examines the prevalence of mental health problems and service utilisation of non-Indigenous Australians by geographic remoteness in rural Australia. Methods A retrospective study of National Coronial Information System data of intentional self-harm deaths in rural New South Wales, Queensland, South Australia and Tasmania for 2010- 2015 from the National Coronial Information System. Results There were 3163 closed cases of intentional self-harm deaths by non-Indigenous Australians for the period 2010-2015. The suicide rate of 12.7 deaths per 100,000 persons was 11% higher than the national Australian rate and increased with remoteness. Among people who died by suicide, up to 56% had a diagnosed mental illness, and a further 24% had undiagnosed symptoms. Reported diagnoses of mental illness decreased with remoteness, as did treatment for mental illness, particularly in men. The most reported diagnoses were mood disorders (70%), psychotic disorders (9%) and anxiety disorders (8%). In the six weeks before suicide, 22% of cases had visited any type of health service at least once, and 6% had visited two or more services. Medication alone accounted for 76% of all cases treated. Conclusions Higher suicide rates in rural areas, which increase with remoteness, may be attributable to decreasing diagnosis and treatment of mental disorders, particularly in men. Less availability of mental health specialists coupled with socio-demographic factors within more remote areas may contribute to lower mental health diagnoses and treatment. Despite an emphasis on improving health-seeking and service accessibility in rural Australia, research is needed to determine factors related to the under-utilisation of services and treatment by specific groups vulnerable to death by suicide.

This paper examines the interrelationship between suicide, health, socioeconomic, and psychosocial factors in contributing to suicide in older adults in rural Australia. Drawing on a coronial dataset of suicide cases and a mixed methods sociological autopsy approach, our study integrated a quantitative analysis of 792 suicide cases with a qualitative analysis of medico-legal reports from 30 cases. The sociological autopsy provided novel insights into the entanglement of policy and service provision at the state-level with individual end-of-life decisions. Particular attention is drawn to age and gendered dimensions of suicide, especially in relation to health and social issues. The study showed a continuity between suicide and the patterning of an individual's life course, including experiences and consequences of inequality and marginality; a desire to meet culturally–normative ideals of autonomy; and a fragmented, under-funded, and intimidating social care system that offered limited options.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread 'natural experiment' of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide cr

Objective: To evaluate three birth-weight (BW) standards (Australian population-based, Fenton and INTERGROWTH-21st) and three estimated-fetal-weight (EFW) standards (Hadlock, INTERGROWTH-21st and WHO) for classifying small-for-gestational age (SGA) and large-for-gestational age (LGA) and predicting adverse perinatal outcomes in preterm and term babies. Methods: This was a nationwide population-based study conducted on a total of 2.4 million singleton births that occurred from 24 + 0 to 40 + 6 weeks' gestation between 2004 and 2013 in Australia. The performance of the growth charts was evaluated according to SGA and LGA classification, and relative risk (RR) and diagnostic accuracy based on the areas under the receiver-operating-characteristics curves (AUCs) for stillbirth, neonatal death, perinatal death, composite morbidity and a composite of perinatal death and morbidity outcomes. The analysis was stratified according to gestational age at delivery (< 37 + 0 vs ≥ 37 + 0 weeks). Results: Following exclusions, 2 392 782 singleton births were analyzed. There were significant differences in the SGA and LGA classification and risk of adverse outcomes between the six BW and EFW standards evaluated. For the term group, compared with the other standards, the INTERGROWTH-21st BW and EFW standards classified half the number of SGA (< 10th centile) babies (3–4% vs 7–11%) and twice the number of LGA (> 90th centile) babies (24–25% vs 8–15%), resulting in a smaller cohort of term SGA at higher risk of adverse outcome and a larger LGA cohort at lower risk of adverse outcome. For term SGA (< 3rd centile) babies, the RR of perinatal death using the two INTERGROWTH-21st standards was up to 1.5-fold higher than those of the other standards (including the WHO-EFW and Hadlock-EFW), while the INTERGROWTH-21st-EFW standard indicated a 12–26% reduced risk of perinatal death for LGA cases across centile thresholds. Conversely, for the preterm group, the WHO-EFW and Hadlock-EFW standards

Background Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES). Methods Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model. Results The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83). Conclusion This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.

Background: Although there is a growing body of literature about the impact of asthma exacerbations during pregnancy on adverse perinatal outcomes, it is still unclear whether asthma exacerbations themselves or asthma severity are the driving factor for negative outcomes. This study aimed to estimate the associations between maternal asthma exacerbations and perinatal outcomes, and whether this differed by asthma treatment regime as a proxy for severity. Methods: We included births of women with asthma in Sweden from July 2006 to November 2013 (n=33829). Asthma exacerbations were defined as unplanned emergency visits/hospitalisations or a short course of oral corticosteroids. Adjusted odds ratios (aOR) were estimated for the associations between exacerbations during pregnancy and perinatal outcomes (small for gestational age (SGA), preterm birth, birthweight and mode of delivery), stratified by preconception treatment regime. Results: Exacerbations occurred in 1430 (4.2%) pregnancies. Exacerbations were associated with reduced birthweight (aOR 1.45, 95% CI 1.24–1.70), and elective (aOR 1.50, 95% CI 1.25–1.79) and emergency caesarean section (aOR 1.35, 95% CI 1.13–1.61). Multiple exacerbations were associated with a 2.6-fold increased odds of SGA (95% CI 1.38–4.82). Amongst women treated prepregnancy with combination therapy ( proxy for moderate–severe asthma), exacerbators were at increased odds of elective (aOR 1.69, 95% CI 1.30–2.2) and emergency (aOR 1.62, 95% CI 1.26–2.08) caesarean section, and SGA (aOR 1.74, 95% CI 1.18–2.57) versus non-exacerbators. Conclusion: Maternal asthma exacerbations increase the risk of SGA and caesarean sections, particularly in women with multiple exacerbations or moderate–severe asthma. Adequate antenatal asthma care is needed to reduce exacerbations and reduce risks of poor outcomes.

Asthma may negatively affect children’s school performance, such as grades and exam results. Results from previous studies have shown varying results and may have suffered from confounding and other biases. We used a Swedish population-based cohort of 570,595 children with data on asthma (including severity and control) in Grades 7–8 and 9, school performance from Grade 9 (grade point sum, non-eligibility for upper secondary school and national test results) and measured confounders from national registers. We used sibling comparisons to account for unmeasured familial factors. Children with asthma and severe asthma performed slightly better in school than children without asthma when adjusting for measured confounders, but the associations were attenuated in sibling comparisons. In contrast, children with uncontrolled asthma performed slightly worse (e.g. Grade 9: βadj = −9.9; 95% CI −12.8 to −7.0; Cohen’s d = 0.16). This association remained for uncontrolled asthma in Grade 9 in sibling comparisons (Grade 9: β = −7.7 points; 95% CI −12.6 to −2.6; Cohen’s d = 0.12), but not for Grades 7–8. The attenuation of estimates when controlling for familial factors using sibling comparisons suggests that the differences were due to familial factors, rather than being causal. The remaining associations in sibling comparisons between uncontrolled asthma in Grade 9 and school performance are consistent with a causal association.

Rationale: Early-life antibiotic use has been associated with the development of atopic diseases, but the aetiology remains unclear. To elucidate the aetiology, we used a discordant twin design to control for genetic and environmental confounding. Methods: We conducted a retrospective cohort study in twins aged 3-10 years from the Netherlands Twin Register (NTR, n=35365) and a replication study in twins aged 9 years from the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7916). Antibiotic use was recorded at age 0-2 years. Doctor-diagnosed asthma and eczema were reported by parents when children were aged 3-12 years in both cohorts. Individuals were included in unmatched analyses and in co-twin control analyses with disease discordant twin pairs. Results: Early-life antibiotic use was associated with increased risk of asthma (NTR OR 1.34, 95% CI 1.28-1.41; CATSS OR 1.45, 95% CI 1.34-1.56) and eczema (NTR OR 1.08, 95% CI 1.03-1.13; CATSS OR 1.07, 95% CI 1.01-1.14) in unmatched analyses. Co-twin analyses in monozygotic and dizygotic twin pairs showed similar results for asthma (NTR OR 1.54, 95% CI 1.20-1.98; CATSS OR 2.00, 95% CI 1.28-3.13), but opposing results for eczema in the NTR (OR 0.99, 95% CI 0.80-1.25) and the CATSS (OR 1.67, 95% CI 1.12-2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS OR 1.45, 95% CI 1.34-1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS OR 1.02, 95% CI 0.88-1.17). Conclusion: Children exposed to early-life antibiotic use, particularly prescribed for respiratory infections, may be at higher risk of asthma. This risk can still be observed when correcting for genetic and environmental factors. Our results could not elucidate whether the relationship between early-life antibiotic use and eczema is confounded by familial and genetic factors.

The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h 2g = 25.6%) than for AOA (onset at ages between 20 and 60 years; h 2g = 10.6%). The genetic correlation (r g ) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h 2g = 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

Depression, anxiety and high neuroticism (affective traits) are often comorbid with asthma. A causal direction between the affective traits and asthma is difficult to determine; however, there may be a common underlying pathway attributable to shared genetic factors. Our aim was to determine whether a common genetic susceptibility exists for asthma and each of the affective traits. An adult cohort from the Swedish Twin Registry underwent questionnaire-based health assessments (n=23693) and genotyping (n=15908). Firstly, questionnaire-based associations between asthma and affective traits were explored. This was followed by genetic analyses: 1) polygenic risk scores (PRS) for affective traits were used as predictors of asthma in the cohort, and 2) genome-wide association results from UK Biobank were used in linkage-disequilibrium score regression (LDSC) to quantify genetic correlations between asthma and affective traits. Analyses found associations between questionnaire-based asthma and affective traits (OR 1.67, 95% CI 1.50-1.86 major depression; OR 1.45, 95% CI 1.30-1.61 anxiety; and OR 1.60, 95% CI 1.40-1.82 high neuroticism). Genetic susceptibility for neuroticism explained the variance in asthma with a dose-response effect; that is, study participants in the highest neuroticism PRS quartile were more likely to have asthma than those in the lowest quartile (OR 1.37, 95% CI 1.17-1.61). Genetic correlations were found between depression and asthma (rg=0.17), but not for anxiety or neuroticism. We conclude that the observed comorbidity between asthma and the affective traits may in part be due to shared genetic influences between asthma and depression (LDSC) and neuroticism (PRS), but not anxiety.

Many epidemiological studies have reported a positive association between prenatal exposure to paracetamol and childhood wheezing and asthma. We investigated whether the link between prenatal analgesic exposure and asthma/wheeze is specific to paracetamol, and whether it is causal or confounded. Using linked Swedish health register data we investigated the relation between various prescribed analgesics in pregnancy and the risk of childhood asthma/wheeze in a population of 492999, and used negative paternal control and sibling comparison approaches to explore unmeasured confounding. After controlling for potential confounders, prescribed opioids, antimigraine drugs and paracetamol were all positively associated with childhood asthma/wheeze risk at all ages (e.g. for asthma/wheeze at age 4 years: adjusted OR 1.39 (95% CI 1.30-1.49), 1.19 (95% CI 1.01-1.40) and 1.47 (95% CI 1.36-1.59) for opioids, antimigraine drugs and paracetamol, respectively). The results of the paternal control analysis did not suggest the presence of unmeasured confounding by genetics or shared environment. However, the sibling control analysis broadly suggested that associations between prenatal exposure to the analgesics and asthma/wheeze were confounded by specific maternal factors (e.g. for asthma/wheeze at age 4 years: adjusted OR 0.91 (95% CI 0.62-1.31), 0.50 (95% CI 0.17-1.45) and 0.80 (95% CI 0.50-1.29) for opioids, antimigraine drugs and paracetamol, respectively). We propose that analgesic use in pregnancy does not cause childhood asthma/wheeze and that the association is confounded by unmeasured factors that are intrinsic to the mother, such as chronic pain or anxiety.

Disproportionate rates of suicide in rural Australia in comparison to metropolitan areas pose a significant public health challenge. The dynamic interrelationship between mental and physical health, social determinants, and suicide in rural Australia is widely acknowledged. Advancement of this knowledge, however, remains hampered by a lack of adequate theory and methods to understand how these factors interact, and the translation of this knowledge into constructive strategies and solutions. This paper presents a protocol for generating a comprehensive dataset of suicide deaths and factors related to suicide in rural Australia, and for building a program of research to improve suicide prevention policy and practice to better address the social determinants of suicide in non-indigenous populations. The two-phased study will use a mixed-methods design informed by intersectionality theory. Phase One will extract, code, and analyse quantitative and qualitative data on suicide in regional and remote Australia from the National Coronial Information System (NCIS). Phase Two will analyse suicide prevention at three interrelated domains: policy, practice, and research, to examine alignment with evidence generated in Phase One. Findings from Phase One and Two will then be integrated to identify key points in suicide prevention policy and practice where action can be initiated.

Background: Medication charting errors occur often and can be harmful for patients. Interventions to improve charting errors have demonstrated some success particularly if the intervention uses multiple approaches including an education component. The aim of this pilot study was to determine whether a multi-faceted intervention, including education of junior doctors and weekday re-charting could reduce in-hospital charting error. Methods: Medication charts (n = 579) of all patients admitted to the medical ward of a medium sized regionally-based hospital in Australia over nine months (baseline and during intervention) were inspected for errors. The intervention ran for three months and involved implementation of a National Inpatient Medication Chart targeted error tool with eight targeted charting requirements which was used for visual reminders in the ward and training of junior doctors. In addition, mid-weekly re-charting (MOWER) was performed by a senior and junior doctor team. Results: The mean number of charting requirement errors significantly reduced during the intervention by 26% from 4.6 ± 1.3 to 3.4 ± 1.7 per chart (p < 0.001). Re-chart errors reduced on average by 50% (4.4 ± 1.4 to 2.2 ± 1.7 per chart, p < 0.001) and primary (initial) charts by 20% (4.6 ± 1.3 to 3.7 ± 1.5 per chart, p < 0.001) during the intervention. Failing to provide indication information for a drug, prescriber name, and failing to use generic rather than brand names were the categories with the most errors at baseline and also showed the largest error reductions during the intervention. Conclusions: A multi-intervention including education of junior doctors, visual reminders and midweek re-charting are effective in reducing the rate of charting errors. We advise that a larger study is now conducted using the same multi-intervention strategy in different ward settings to evaluate feasibility and sustainability of this intervention.

To evaluate associations between maternal anxiety or depression and adverse pregnancy outcomes, taking possible familial confounding and interaction with asthma into account, we conducted a cohort study of all singleton births in Sweden 2001–2013. We retrieved information about pregnancy, diagnoses of anxiety/depression, asthma, and prescribed medication from the Swedish Medical Birth, National Patient, and Prescribed Drug Registers. We estimated associations with regression models, performed cousin and sibling comparisons, and calculated interactions. In 950 301 identified pregnancies; 5.9% had anxiety/depression and 4.0% had asthma. Anxiety/depression was associated with adverse pregnancy outcomes (e.g. preeclampsia, adjusted Odds Ratio 1.17 (95% Confidence Interval 1.12, 1.22), instrumental delivery (1.14 (1.10, 1.18)), elective (1.62 (1.57, 1.68)) and emergency (1.32 (1.28, 1.35)) caesarean section (CS)). Their children had lower birth weight (−54 g (−59, −49)) and shorter gestational age (−0.29 weeks (−0.31, −0.28)). Associations were not confounded by familial factors and asthma did not modify the effect of anxiety/depression for outcomes other than elective CS, p < 0.001. In women with anxiety/depression diagnosis, untreated women had higher odds of elective CS compared to women on medication (1.30 (1.17, 1.43)). In conclusion, anxiety/depression should be considered when evaluating pregnant women’s risk of complications such as preeclampsia and non-vaginal deliveries.

Background: Over a fifth of children and adolescents suffer with asthma or atopic disease. It is unclear whether asthma impacts academic performance in children and adolescents, and little is known about the association of eczema, food allergy or hayfever and academic performance. Objective: To examine whether asthma, eczema, food allergy or hayfever impacts on adolescent academic performance and to assess the role of unmeasured confounding. Methods: This study used the Childhood and Adolescent Twin Study of Sweden cohort born 1992-1998. At age 9-12 years, parents reported on their child's ever or current asthma, eczema, food allergy and hayfever status (n = 10 963). At age 15, linked national patient and medication register information was used to create current and ever asthma definitions including severe and uncontrolled asthma for the same children. Academic outcomes in Grade 9 (age 15-16 years) included: eligibility for high school (Grades 10-12), and total mark of the best 16 subject units, retrieved from the Grade 9 academic register. Whole cohort analyses adjusted for known covariates were performed, and co-twin control analyses to assess unmeasured confounders. Results: There were no associations found for asthma or food allergy at 9-12 years and academic outcomes in adolescence. In addition, at age 15, there were no statistically significant associations with current, ever, severe or uncontrolled asthma and academic outcomes. Eczema and hayfever at age 9-12 years were found to be positively associated with academic outcomes; however, co-twin control analyses did not support these findings, suggesting the main analyses may be subject to unmeasured confounding. Conclusion and clinical relevance: Having asthma or an atopic disease during childhood or adolescence does not negatively impact on academic performance. This information can be used by clinicians when talking with children and parents about the implications of living with asthma or atopic disease.

'Asthma' is a complex disease that encapsulates a heterogeneous group of phenotypes and endotypes. Research to understand these phenotypes has previously been based on longitudinal wheeze patterns or hypothesis-driven observational criteria. The aim of this study was to use data-driven machine learning to identify asthma and wheeze phenotypes in children based on symptom and symptom history data, and, to further characterize these phenotypes. The study population included an asthma-rich population of twins in Sweden aged 9-15 years (n = 752). Latent class analysis using current and historical clinical symptom data generated asthma and wheeze phenotypes. Characterization was then performed with regression analyses using diagnostic data: lung function and immunological biomarkers, parent-reported medication use and risk-factors. The latent class analysis identified four asthma/wheeze phenotypes: early transient wheeze (15%); current wheeze/asthma (5%); mild asthma (9%), moderate asthma (10%) and a healthy phenotype (61%). All wheeze and asthma phenotypes were associated with reduced lung function and risk of hayfever compared to healthy. Children with mild and moderate asthma phenotypes were also more likely to have eczema, allergic sensitization and a family history of asthma. Furthermore, those with moderate asthma phenotype had a higher eosinophil concentration (β 0.21, 95%CI 0.12, 0.30) compared to healthy and used short-term relievers at a higher rate than children with mild asthma phenotype (RR 2.4, 95%CI 1.2-4.9). In conclusion, using a data driven approach we identified four wheeze/asthma phenotypes which were validated with further characterization as unique from one another and which can be adapted for use by the clinician or researcher.

Purpose: Risk factors and consequences of asthma can be studied by using validated questionnaires. The overall objective of this study was to assess the agreement of parental-reported asthma-related questions regarding their children against Swedish health care registers. Methods: We linked a population-based twin cohort of 27 055 children aged 9 to 12 years to the Swedish Prescribed Drug Register, National Patient Register, and the primary care register. Parent-reported asthma was obtained from questionnaires, and diagnoses and medication were retrieved from the registers. For the agreement between the questionnaire and the registers, Cohen's kappa was estimated. Results: The kappa of the “reported ever asthma” against a “register-based ever asthma” was 0.69 and 0.57 between the parental-“reported doctor's diagnosis” and “register-based doctor's diagnosis.” The highest agreement between “reported current asthma” and “register-based current asthma” with at least 1 dispensed medication or a diagnosis applied to different time windows was seen for an 18-month window (kappa = 0.70). Conclusions: We found that parent-reported asthma-related questions showed on average good agreement with the Swedish health care registers. This implies that in-depth questionnaires with rich information on phenotypes are suitable proxies for asthma in general and can be used for health care research purposes.

Background: Prenatal maternal stress may influence offspring's atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic-pituitary axis (HPA), leading to Th2-biased cell differentiation in the foetus. We undertook a systematic review and meta-analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring. Methods: We searched 11 electronic databases from 1960 to 2016, searched the grey literature and contacted experts in the field. Type of stress indicator included mood disorders, anxiety, exposure to violence, bereavement and socio-economic problems occurring during pregnancy, both objectively and subjectively measured. We included all possible asthma and IgE-mediated allergy outcomes. We conducted random-effects meta-analyses to synthesize the data. Results: We identified 9779 papers of which 30 studies (enrolling >6 million participants) satisfied inclusion criteria. The quality of 25 studies was moderate, 4 were strong, and one was weak. Maternal exposure to any type of stressors was associated with an increased risk of offspring atopic eczema/dermatitis (OR 1.34, 95% CI 1.22-1.47), allergic rhinitis (OR 1.30, 95% CI 1.04-1.62), wheeze (OR 1.34, 95% CI 1.16-1.54) and asthma (OR 1.15, 95% CI 1.04-1.27). Exposure to anxiety and depression had strongest effect compared to other stressors. Exposure during the third trimester had the greatest impact compared to first and second trimesters. The increased risk was stronger for early-onset and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95% CI 1.10-1.48) or a spouse (HR 1.40, 95% CI 1.03-1.90) increased the risk of offspring asthma. Conclusions: Exposure to prenatal maternal psychosocial stress was associated with increased risk, albeit modestly, of asthma and allergy in the offspring. The pronounced risk during the third trimester may represent cumulative stress exposure throughout pre

Background: Children with asthma and atopic diseases have an increased risk of depression or anxiety. Each of these diseases has strong genetic and environmental components; therefore, it seems likely that there is a shared liability rather than causative risk. Objective: To investigate the existence and nature of familial aggregation for the comorbidity of atopic diseases and depression or anxiety. Methods: Participants came from the Childhood and Adolescent Twin Study in Sweden (CATSS), n = 14 197. Current and ever asthma, eczema, hay fever and food allergy were reported by parents. Internalizing disorders were identified using validated questionnaires. Familial co-aggregation analysis compared monozygotic (MZ) twins and same-sex dizygotic (DZ) twins for atopic disease in 1 twin with internalizing disorder in the other to test for genetic liability. Several familial liability candidates were also tested including parental education, recent maternal psychological stress, childhood family trauma and parental country of birth. Results: Familial co-aggregation analysis found that if 1 twin had at least 1 current atopic disease the partner twin was at risk of having an internalizing disorder regardless of their own atopic status (adjusted OR 1.22 (95% CI 1.08, 1.37). Similar results were found for each atopic disease ever and current. MZ associations were not higher than DZ associations, suggesting that the liability is not genetic in nature. Including other familial candidates to the models made little difference to effect estimates. Conclusions and Clinical Relevance: Atopic diseases and depression or anxiety tend to occur together in families; therefore, when treating for 1 disease, the physician should consider comorbidity in both the individual and the individual's siblings. We did not find evidence to support a genetic explanation for comorbidity, and further exploration is needed to disentangle the environmental and epigenetic reasons for familial aggregation.

Background: Previous research has found that maternal stress during pregnancy increases the risk of offspring asthma. However, whether this association is consistent with a causal interpretation has never been tested. The objective is to determine whether there is a critical exposure period for maternal depression or anxiety on offspring asthma or whether cumulative exposure is most important, and to investigate evidence of confounding. Methods: The study population included all children born in Sweden from July 2006 to December 2009 (n = 360 526). Information about childhood asthma, maternal depression or anxiety (diagnosis or medication) and covariates was obtained from the Swedish national health registers. The associations between exposure periods (pre-conception, pregnancy, postnatal or current) and childhood asthma were estimated using structured life course approach hypothesis testing. Paternal and cousin analyses were used to test for evidence of confounding from shared genes and environment. Results: For childhood asthma, cumulative exposure best described the effect of exposure to maternal depression or anxiety up to a maximum of any two exposure periods [adjusted odds ratio 1.44, 95% confidence interval (CI) 1.38, 1.52]. The hypotheses of a critical period were not supported. The paternal and cousin analyses indicated minimal influence from familial confounding. Conclusions: These findings support an association between cumulative exposure to maternal depression or anxiety and asthma development in offspring. This association is unique for maternal depression or anxiety and not due to familial confounding. The clinical implication is that effective psychological management of women with chronic distress may reduce offspring asthma risk.

Background: Developmental Origins of Health and Disease Hypothesis (DOHaD) studies are often observational in nature and are therefore prone to biases from loss to follow-up and unmeasured confounding. Register-based studies can reduce these issues since they allow almost complete follow-up and provide information on fathers that can be used in a negative control analysis to assess the impact of unmeasured confounding. Aim: The aim of this study was to propose a causal model for testing DOHaD using paternal exposure as a negative control, and its application to maternal distress in pregnancy and offspring asthma. Methods: A causal diagram including shared and parent-specific measured and unmeasured confounders for maternal (fetal) and paternal exposures is proposed. The case study consisted of all children born in Sweden from July 2006 to December 2008 (n=254,150). Information about childhood asthma, parental distress and covariates was obtained from the Swedish national health registers. Associations between maternal and paternal distress during pregnancy and offspring asthma at age five years were assessed separately and with mutual adjustment for the other parent's distress measure, as well as for shared confounders. Results: Maternal distress during pregnancy was associated with offspring asthma risk; mutually adjusted odds ratio (OR) (OR 1.32, 95% CI 1.23, 1.43). The mutually adjusted paternal distress-'offspring asthma analysis (OR 1.05, 95% CI 0.97, 1.13) indicated no evidence for unmeasured confounding shared by the mother and father. Conclusions: Using paternal exposure in a negative control model to test the robustness of fetal programming hypotheses can be a relatively simple extension of conventional observational studies but limitations need to be considered.

Objective: There is some evidence to suggest that safety on small-area farms may not be high priority due to economic constraints and lack of knowledge. This has important ramifications for injury and economic burden. The objective of this research was to conduct a pilot study to investigate whether small- to medium-area farms implement fewer safety practices than large-area farms. Methods: Farmers were recruited from farm safety training days, field days, and produce stores in rural New South Wales (NSW), Australia. Small- and medium-area farms less than 500 ha (1235 acres) in size were aggregated for analysis and compared with large-area farms (≥500 ha) for survey items, including safety equipment owned and used, safety practices protecting children, barriers to improving safety, and causes of injury. Results: Overall, small/medium-area farms were found to own less safety equipment and to employ less safety practices than large-area farms. In particular, fewer tractors were fitted with rollover protection structures, there was less signage, less hearing protection, and fewer machinery guides. Injury rates were slightly less for small/medium-area farms, particularly involving vehicles. Small- and medium-area farmers were more likely to report lack of skills as barriers to making safety improvements. Conclusion: This pilot study found some evidence that small/medium-area farms implement fewer safety practices than large-area farms. A larger study is warranted to investigate this further, with particular focus on barriers and ways to overcome them. This could have important ramifications for government policies supporting struggling farmers on small/medium-area farms.

Objective: To investigate the relationship between breastfeeding and snoring in childhood. Methods: In a cohort of children with a family history of asthma who were recruited antenatally we prospectively recorded data on infant feeding practices throughout the first year of life. Snoring status and witnessed sleep apnea were measured at age 8 years by parent-completed questionnaire. Associations were estimated by logistic regression with, and without, adjustment for sets of confounders designed to exclude biasing effects. Results: Habitual snoring was reported in 18.8% of the sample, and witnessed apnea in 2.7%. Any breastfeeding for longer than one month was associated with a reduced risk of habitual snoring at age 8 (adjusted OR 0.48, 95% CI 0.29 to 0.81) and duration of breastfeeding was inversely associated with the prevalence of habitual snoring (adjusted OR 0.79, 95% CI 0.62 to 1.00). Any breastfeeding for longer than 1 month was associated with a lower risk of witnessed sleep apnea (adjusted OR 0.17, 95% CI 0.04 to 0.71). The protective associations were not mediated by BMI, current asthma, atopy or rhinitis at age 8 years. Conclusions: Breastfeeding for longer than one month decreases the risk of habitual snoring and witnessed apneas in this cohort of children with a family history of asthma. The underlying mechanism remains unclear but the finding would be consistent with a beneficial effect of the breast in the mouth on oropharyngeal development with consequent protection against upper airway dysfunction causing sleep-disordered breathing. © 2014 Brew et al.