Causes and consequences of stress and tobacco exposure in utero on birth size, asthma and academic achievement

The objective of this thesis was to further the understanding of the consequences of stress and smoking during pregnancy, the causes of intrauterine growth and asthma as well as the consequences of asthma on school performance and to explore explanations of observed associations. In Study I we investigated the associations between four measures of subjective distress and cortisol levels in early and late pregnancy and perinatal outcomes. All estimated associations were small and most statistically non-significant. However, for birth weight by gestational age the estimated associations with subjective distress were statistically significant, indicating higher birth weight with higher distress. Results were similar in early and late pregnancy. In Study II we explored an intergenerational effect of smoking during pregnancy (SDP) on the grandchildren’s intrauterine growth. The grandchildren of maternal grandmothers who smoked during pregnancy had a slightly higher risk of being large for gestational age, which may be partly explained by a higher obesity rate among their daughters (grandchild’s mother). In contrast, the grandchildren of paternal grandmothers who smoked during pregnancy had slightly higher risk of being small for gestational age, which may be partly explained by a higher SDP rate among their daughters-in-law (grandchild’s mother). Sensitivity analysis with regard to unmeasured confounding indicated that this may explain the associations. In Study III, we explored the association between tobacco use during pregnancy and offspring asthma/wheeze and the potential role of nicotine and familial factors such as genes and environment shared within the family. We found that SDP was associated with a higher risk of asthma/wheeze in the first two years of life, but not at higher ages. Analysis of the association between oral snuff use in pregnancy, i.e. exposure to nicotine without combustion toxins, and asthma/wheeze indicated no clear association. The sibling comparisons showed lower estimates. Taken together this indicates that the role of nicotine in the association between SDP and asthma/wheeze may be limited, while familial factors seem important. In Study IV we examined if adolescents with asthma in school Grades 7-8 and 9 perform worse in school compared to adolescents without asthma. Our results indicated that school performance of adolescents with asthma was somewhat better than among those without asthma, but also that asthma severity and control were important. Adolescents with severe, but controlled asthma, performed somewhat better than those without asthma, while children with uncontrolled asthma performed somewhat worse. Sibling analyses indicated familial factors explained most associations, with the exception of an association between uncontrolled asthma in Grade 9 and slightly lower school performance. In conclusion, considering other known detrimental effects of the risk factors investigated in this thesis, our findings of no or very modest associations, should not in any way be interpreted as excuses for ignoring stress in pregnant women, continue smoking during pregnancy or give up the strife for asthma control in children and adolescents

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

NonePublishe

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

Students’ understanding of causation in pricing: a phenomenographic analysis

The aim of this study is to extend previous research on conceptions of price by highlighting variation in students’ understanding of causality. It also aims to offer a new way of using ’dimensions of variation’ in phenomenographic research to analyse the structure of conceptions of complex phenomena. The study uses data from 96 upper secondary students who were asked to provide written answers to two problems before and after a short programme of teaching. This yielded a total of 349 open responses which were analysed phenomenographically. The study revealed four qualitatively distinct ways of understanding causation in pricing. It also revealed new insights in how different dimensions of variation in conceptions of pricing are related to each other. The study suggests that the form of a problem posed to students will affect the dimensions of variation in conceptions that are exposed. Conclusions drawn are relevant for research and teaching

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

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

NoneAccepte

Puberty and asthma in a cohort of Swedish children

VRAstma och allergiförbundetHjärt och lungfondenManuscrip