Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study.

Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study.

BACKGROUND: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations. OBJECTIVES: To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease. METHODS: We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability. RESULTS: Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects. CONCLUSIONS: Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.

Seasonal trends in house dust mite allergen in children's beds over a 7-year period.

BACKGROUND: House dust mite (HDM) allergy is closely linked to the expression of asthma and other allergic diseases. Understanding factors influencing variation in allergen may help in controlling allergic disease. The objective of this study was to investigate the effects of seasonal changes in climate, type of bed used in very early childhood and anti-mite interventions on HDM allergen concentration. METHODS: Participants were enrolled in a randomized-controlled trial of HDM avoidance. Der p 1 was measured in dust samples from children's beds on 13 occasions, from birth to age 5 years, between 1997 and 2004. Bed types were categorized as bassinette, cot or bed. The effects of study month, type of bed and intervention group on HDM allergen concentration were estimated by multiple linear regression. The relation between climatic variables and HDM allergen concentration was investigated using a polynomial distributed lag model. RESULTS: House dust mite allergen concentrations were initially low in cots and bassinettes in 1997/1998, peaked in bassinettes and beds between 1999 and 2001 and then slowly declined during the period 2002/2004. Seasonal fluctuations occurred with minima in summer and two- to threefold higher maxima during late autumn. Allergen peaks were correlated with relative humidity peaks 2 months previously. Seasonal changes in allergen were not affected by the HDM avoidance intervention. CONCLUSIONS: House dust mite allergen concentrations in Sydney beds fluctuate approximately two- to threefold on an annual cycle, partly determined by relative humidity, with peaks in late autumn and minima in summer. Fluctuations of this magnitude might be sufficient to influence asthma symptoms.

Low socioeconomic status as a risk factor for asthma, rhinitis and sensitization at 4 years in a birth cohort.

BACKGROUND: The relation between socioeconomic status and allergic diseases in childhood is controversial. Some studies have proposed childhood asthma to be more common in families with low socioeconomic status, while sensitization to airborne allergens seems to be more frequent in individuals with higher socioeconomic status in childhood. OBJECTIVE: To assess the relation between socioeconomic status and asthma, rhinitis and sensitization in an unselected prospective birth cohort. METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors, socioeconomic status (parental occupation), and symptoms of allergic disease at birth, 1, 2 and 4 years of age. Blood samples taken at 4 years from 2614 children were analysed for specific IgE to common airborne and food allergens. Odds ratios (OR) and 95% confidence intervals (CI) for various outcomes in relation to socioeconomic status were estimated with a multiple logistic regression model, adjusting for potential confounders such as heredity for allergic diseases, maternal smoking, short duration of breastfeeding and house construction. RESULTS: There was a decreasing risk of asthma and rhinitis with increasing socioeconomic status. The OR for asthma was 0.33 (95% CI 0.17-0.66) and for rhinitis 0.50 (0.32-0.79) comparing the highest and the lowest socioeconomic groups, with a tendency to stronger effects in those with heredity for allergic disease. The risk of sensitization to food allergens also decreased with increasing socioeconomic status; OR 0.65 (0.41-1.02) in the highest socioeconomic group (Ptrend=0.03), which was not clearly seen for airborne allergens. CONCLUSION: Asthma, rhinitis and sensitization is more common in lower than in higher socioeconomic groups after adjustment for traditional risk factors. This may be related to additional uncontrolled differences in life style and environmental exposures between the groups, and calls for further studies.

Strategies for preventing wheezing and asthma in small children.

OBJECTIVE: To assess the effects of living in agreement with allergy preventive guidelines on wheezing and asthma at 2 years of age. DESIGN: Prospective birth cohort study (BAMSE). Questionnaires on heredity and environmental factors were answered when the child was 2 months, and detailed questionnaires on symptoms at 1 and 2 years of age. PARTICIPANTS: 4089 children, born during 1994-1996. SETTING: Child Health Centres in central and north-western parts of Stockholm, Sweden. MAIN OUTCOME MEASURES: Wheezing and asthma up to the age of 2. RESULTS: The effects of preventive guidelines regarding breastfeeding, maternal tobacco smoke and home dampness on wheezing and asthma were assessed in multiple logistic regression models. The cumulative incidence of recurrent wheezing at 2 years of age was 12.6% and of asthma 6.8% among those with a lifestyle in agreement with all guidelines and 24.1 and 17.9%, respectively, in families exposed to at least two of the three risk factors. Among children with no heredity, family lifestyle according to the guidelines gave a twofold reduction of asthma (5.3 vs. 10.5%), while the group with heredity had a threefold reduction (9.1 vs. 27.3%). The attributable fraction for asthma associated with the guidelines was 23% in total and 33% among those with heredity. CONCLUSION: In this observational study, family lifestyle according to preventive guidelines is associated with an important reduction of recurrent wheezing and asthma at 2 years of age, especially among children with allergic heredity. A follow-up will determine whether there still a risk reduction of both symptoms and disease.