Birth mode of delivery in the modern delivery ward : indication improves understanding of childhood asthma

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Population-based data on asthma and allergic disease call for advanced epidemiologic methods

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The association between caesarean section and asthma or allergic disease continues to challenge

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Twins' risk of childhood asthma mediated by gestational age and birthweight

Background: Children born with low gestational age (GA) or low birth weight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW, and have been hypothesized to comprise a high risk population for asthma. Many previous studies have not accounted for potential confounders or mediators. Objective: To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW. Methods: The study population consisted of two cohorts including all children born in Sweden from January 1st 1993 to June 1st 2001 (n=756,363 singletons, n=22,478 twins) and July 1st 2005 to December 31st 2009 (n=456,239 singletons, n=12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birth weight. Results: In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results. Conclusions: Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding.NonePublishe

Cat and house dust mite allergen content is stable in frozen dust over time

Background: Dust from indoor environments consists of animal allergens, pollen, endotoxins and other substances which may exacerbate symptoms in sensitive individuals. In prospective cohort studies, dust is often collected from indoor environments in order to assess allergen exposure and possible relationships to health outcomes. Typically, large numbers of samples are collected and kept frozen until further analysis, sometimes several years later. To date, there is insufficient knowledge about what happens to the dust and its contents during storage. Objectives: In the present study, our aim was to analyse allergen content over a 30 month period frozen dust collected from beds in homes in order to simulate a study design of exposure assessment commonly used in epidemiological studies. Methods: Thirty-seven dust samples from mattresses in homes were collected using a Duststream dust collector. Each dust sample was subdivided into six aliquots. One tube (baseline) was extracted and analysed for cat and HDM allergen content using ELISA, all other tubes were stored at -80°C until further handling. Approximately every six months (6, 12, 18 and 30 months), dust from one tube was thawed, extracted and analysed the same way. Data was log-transformed and analysed using linear regression. Results: No trend for decreasing or increasing cat (p=0.606) or house dust mite (p=0.928)allergen levels could be observed over time. Levels of cat allergen were considerably higher in mattresses from homes with cats compared to homes without cats (p<0.001). Conclusion: It is important to assess the allergen stability in dust before designing costly and labour-intensive studies of allergen exposure and health outcomes, commonly used in environmental epidemiology. Although the present study showed that cat and HDM allergens 3 remained stable in dust stored at -80°C during a 2.5 year period, analyses of other allergens or substances in frozen dust is desirable as well as evaluating the effect of longer storage times.VetenskapsrådetAFAManuscrip

Association between childhood asthma and ADHD symptoms in adolescence : a prospective population-based twin study

BACKGROUND: Cross-sectional studies report a relationship between childhood asthma and attention-deficit hyperactivity disorder (ADHD) symptoms, but the mechanisms are yet unclear. Our objective was to investigate the longitudinal link between childhood asthma and the two dimensions of ADHD (hyperactivity-impulsivity, HI, and inattention, IN) in adolescence. We also aimed to explore the genetic and environmental contributions and the impact of asthma medication. METHODS: Data on asthma, HI and IN, birth weight, socioeconomic status, zygosity, and medication were collected from the Swedish Medical Birth Register and through parental questionnaires at ages 8-9 and 13-14 years on 1480 Swedish twin pairs born 1985-1986. The association between asthma at age 8-9 and ADHD symptoms at age 13-14 was assessed with generalized estimating equations, and twin analyses to assess the genetic or environmental determinants were performed. RESULTS: Children with asthma at age 8-9 had an almost twofold increased risk of having one or more symptom of HI (OR 1.88, 95% CI 1.18-3.00) and a more than twofold increased risk to have three symptoms or more of HI (OR 2.73, 95% CI 1.49-5.00) at age 13-14, independent of asthma medication. For IN, no significant relationship was seen. Results from twin modeling indicate that 68% of the phenotypic correlation between asthma and HI (r=0.23, 0.04-0.37) was because of genetic influences. CONCLUSIONS: Our findings suggest that childhood asthma is associated with subsequent development of HI in early adolescence, which could be partly explained by genetic influences. Early strategies to identify children at risk may reduce burden of the disease in adolescence.VRALFThe Centre for Allergy ResearchThe Strategic Research Program in Epidemiology at Karolinska Institutet.Manuscrip

The impact of birth mode of delivery on childhood asthma and allergic diseases : a sibling study

Background: Caesarean section (CS) has been reported to increase the risk of asthma in offspring. This may be due to that infants delivered by CS are unexposed to vaginal flora, according to the ‘hygiene hypothesis’. Objective: Our aim was to investigate if CS increases risk of childhood asthma, and if the risk increase remains after adjustment for familial confounding using sibling design. Methods: A register-based cohort study with 87 500 Swedish sibling pairs was undertaken. Asthma outcome variables were collected from national health registers as diagnosis or asthma medication (ICD-10 J45-J46; ATC code R03) during the 10th or 13th year of life (year of follow-up). Mode of delivery and confounders were retrieved from the Medical Birth Register. The data were analysed both as a cohort and with sibling control analysis which adjusts for unmeasured familial confounding. Results: In the cohort analyses, there was an increased risk of asthma medication and asthma diagnosis during year of follow-up in children born with CS (adjusted ORs, 95% CI 1.13, 1.04–1.24 and 1.10, 1.03–1.18 respectively). When separating between emergency and elective CS the effect on asthma medication remained for emergency CS, but not for elective CS, while both groups had significant effects on asthma diagnosis compared with vaginal delivery. In sibling control analyses, the effect of elective CS on asthma disappeared, while similar but non-significant ORs of medication were obtained for emergency CS. Conclusions and Clinical Relevance: An increased risk of asthma medication in the group born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora. A more probable explanation should be sought in the indications for emergency CS.Swedish Research CouncilCentre for Allergy ResearchStiftelsen Frimurare-Barnhuset i StockholmALF KI/SLLPublishe

Fetal growth and risk of childhood asthma and allergic disease

Introduction: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective: This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods: PubMed-search on pre-defined terms and cross-references. Results: Several studies have shown a correlation between low birth weight and/or gesta- tional age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subse- quent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that dis- eases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance: Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.Swedish Research CouncilALF KI/SLLStrategic Research Program in Epidemiology at Karolinska InstitutetPublishe

No association between macrolide treatment in infancy and later pyloric stenosis in Sweden

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