Asthma, a huge burden on millions of individuals worldwide, is one of the most important public health issues in many countries. As genetic and   environmental factors interact, asthma may be programmed very early in life, perhaps even in utero. The aim of this thesis was to assess the impact of gestational age, cord blood immunoglobulin E (IgE), a family history of asthma, migration, and pertussis immunization in early life on the development of asthma in child and adult populations. As a proxy for asthma disease, dispensed asthma medication was used as the main outcome variable based on data from the Swedish Prescribed Drug  Register. Data from other national registers were used to control for  confounders. Three of our studies were based on national cohorts, and one on a local birth cohort that was initiated in 1974–75. Gestational age had an inverse dose-response relationship with dispensed asthma medication in 6– to 19-year-olds. Odds ratios for dispensed asthma medication increased with degree of prematurity compared with children born in term. Furthermore, asthma medication was more likely to be dispensed among children and adolescents born early term after 37–38 weeks’ gestation than among those at the same age who were born in term. Elevated cord blood IgE and a family history of asthma in infancy were associated with a two- to threefold increased likelihood of dispensed asthma medication and self-reported allergen-induced respiratory symptoms at the age of 32–34 years, but the predictive power was poor. Age at migration had an inverse dose-response relationship with dispensed asthma medication at the age of 6–25 years in adoptees and foreign-born children with foreign-born parents. International adoptees and children born in Sweden to foreign-born parents had three- to fourfold higher rates of asthma medication compared with foreign-born children who were raised by their foreign-born birth parents. No association was found between pertussis immunization in early infancy and dispensed asthma medication in 15-year-olds. The type of vaccine or vaccine schedule did not affect the outcome. Fetal life is a vulnerable period. This thesis strengthens the evidence that every week of gestation is important for lung maturation. Cord blood IgE, however, did not predict the risk of asthma in adults. Furthermore, the study of migrating populations demonstrated that environmental changes at any age during childhood may affect the risk of asthma. Another, important public health message from this thesis is that vaccination against pertussis in early childhood can be considered safe with respect to the long-term development of asthma.

No description available.

This thesis explored cognitive, psychosocial, and physical domains of wellbeing to find out their contribution to successful ageing in 70-year old individuals. Discovering groups with different patterns of wellbeing and their correlates may be informative about what constitutes success in old age. The objectives were to find out whether distinct groups within and across domains of wellbeing existed, and to find out the variables associated with the resulting groups. Using a cross-sectional design on the Lothian Birth Cohort 1936 (LBC1936, maximum n = 1091), which is a group of community-dwelling 70 year-olds, latent class analysis (LCA) was used to explore possible patterns of ageing in domains of cognitive, psychosocial, and physical function. Demographic, personality, and lifestyle variables that were not used in the LCA were used to characterise the resulting groups. The first study investigated cognitive ability. Individuals were grouped according to their scores on general cognitive ability (g), memory, and speed. I accepted a 3-group solution, including High- (n = 749, 69%), Average- (n = 303, 28%), and Low- (n = 39, 4%) cognition groups. Results indicated the presence of a strong dimension: people who did well on one component also did well on others, and failed to show any indication of uneven patterns of scores. In the second study on psychosocial wellbeing individuals were grouped according to their scores on physical function, quality of life, and emotional wellbeing. A 5-group solution was accepted. High (n =515, 42.7%), Average (n = 417, 38.3%), and Poor (n = 37, 3.4%) Wellbeing groups were identified; however, contrasting patterns of wellbeing across components were noticed in the two other groups: one group scored relatively highly on physical function, but low on emotional wellbeing (High Function/ Low Spirits, n = 60, 5.5%), while another group showed low physical function but relatively high emotional wellbeing (Low Function/High Spirits, n = 62, 5.7%). The next study investigated the physical fitness domain: groups were determined on physical fitness, lack of inflammation, and lack of morbidity. Two groups, High Physical Fitness (n = 757, 73.3%) and Low Physical Fitness (n = 291, 26.7%) were identified, which, like the cognitive domain, also indicated a continuous pattern of wellbeing. In the final study individuals were grouped according to their scores on all variables reflecting cognitive, psychosocial, and physical function. I identified 3 groups showing high or uneven patterns of wellbeing. The majority of individuals fell in the High Wellbeing group (n = 712, 65.3%). The two other groups contained either individuals scoring high on cognitive measures but poorly on psychosocial and physical measures (the Low Bio-Psychosocial group, n = 158, 14.5%), or individuals scoring low on cognitive measures but highly on psychosocial and physical measures (the Low Cognition group, n = 221, 20.3%). Intelligence, personality and health behaviours showed salient differences amongst the groups in all studies. Overall, high childhood cognitive ability, low scores on Neuroticism, and avoiding smoking were associated with high wellbeing. Overall, results demonstrated that although wellbeing in old age is primarily dimensional, there is evidence of groups showing uneven patterns of function, indicating that individuals could show relatively successful patterns in some areas of wellbeing despite relatively poor functioning in other areas. Awareness of the importance of lifelong intelligence and personality traits and health practices to later-life wellbeing amongst health-care professionals and policymakers may help address risk-prevention, and improve compliance and patient-practitioner relationships to reduce health inequalities.

Cord blood IgE has previously been studied as a possible predictor of asthma and allergic diseases. Results from different studies have been contradictory, and most have focused on high-risk infants and early infancy. Few studies have followed their study population into adulthood. This study assessed whether cord blood IgE levels and a family history of asthma were associated with, and could predict, asthma medication and allergy-related respiratory symptoms in adults. A follow-up was carried out in a Swedish birth cohort comprising 1701 consecutively born children. In all, 1661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1227 responded to a postal questionnaire. Cord blood IgE and family history of asthma were correlated with reported respiratory symptoms and dispensed asthma medication at 32–34 years. Elevated cord blood IgE was associated with a two- to threefold increased risk of pollen-induced respiratory symptoms and dispensed anti-inflammatory asthma medication. Similarly, a family history of asthma was associated with an increased risk of pollen-induced respiratory symptoms and anti-inflammatory medication. However, only 8% of the individuals with elevated cord blood IgE or a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication at follow-up. Elevated cord blood IgE and a positive family history of asthma were associated with reported respiratory symptoms and dispensed asthma medication in adulthood, but their predictive power was poor in this long-time follow-up. / <p>The status of this article was on the day of the defence date <em>Manuscript</em>.</p>

With an increase in life expectancy, the number of older people affected by cognitive decline and dementia is rising, causing major, global public health concerns. However, there is substantial variation in the rate and magnitude of cognitive decline experienced among ageing individuals. Evidence suggests that many age-associated changes in cognitive functioning can be explained by modifiable lifestyle factors such as smoking, physical activity and diet choices. The weight of the evidence supports the promotion of a healthy lifestyle as an effective strategy for healthy cognitive ageing. Many epidemiological studies have drawn causal conclusions with regard to the positive and direct benefits of lifestyle, yet few have considered the possible confounding role of prior cognitive ability in explaining the lifestyle and cognition relationship in older age. Given the potential for reverse causation, whereby better prior cognitive functioning leads to a greater uptake of healthy behaviours rather than vice versa, it is a mechanism which should be studied, but rarely is. The present thesis focuses on the possible confounding effect of prior cognitive ability on the cross-sectional relationships between lifestyle factors and cognitive ability domains in later-life. The core of the thesis is a series of independent, peer-reviewed (six first-author and one co-author) journal articles in the public domain. Data were derived from the Lothian Birth Cohort 1936 study (n = 1091), a sample of relatively healthy, community-dwelling men and women aged 70 years from Edinburgh, Scotland, for whom childhood (age 11) mental test scores are available. The lifestyle factors investigated were caffeine consumption, alcohol consumption, dietary patterns, body mass index, smoking, serum cholesterol, and physical activity. Cognitive function was assessed across five major ageing-related domains: age 70 IQ (based on the same test that was taken in childhood), general cognitive ability (g), processing speed, memory, and verbal ability. General linear models (ANCOVA) were adjusted for the following covariates: age; sex; childhood cognitive ability; and socioeconomic status (SES). Other potential covariates were additionally adjusted for as necessary. Overall, the positive and significant associations observed between ‘healthy’ lifestyle factors and better cognitive functions at age 70 were consistent with previous research; their effect size was around 1% of the variance in cognitive tests scores. However, these relationships were markedly attenuated (by on average 80%) by a higher childhood cognitive ability and adult SES; for the most part, associations were reduced to non-significance. None of the lifestyle factors were consistent predictors of performance across cognitive domains, though smoking avoidance, a physically active lifestyle, and moderate intake of alcohol, appeared to have the most potential. The key novel finding of this thesis is that, in addition to having predictive value for lifestyle choices over 60 years later, cognitive ability at age 11 accounted for the majority of the cross-sectional associations between lifestyle factors and cognitive abilities in later-life. This finding is consistent with the theory of confounding or even reverse causation. That is, individuals with higher lifetime ‘trait’ cognitive ability may be more likely to adopt a lifestyle which protects against cognitive decline. Rather than a unidirectional or indirect effect of health behaviours on cognitive function, the present findings suggest there may be a dynamic cycle involving cognition, self-management of health and ultimate cognitive outcomes.

I den här uppsatsen undersöks hur hälsa påverkar sambandet mellan social bakgrund och utbildning. Att förstå hur delar av människors liv påverkas av deras ställning i samhället är endast en del av ledet i vetenskapens försök att förstå fenomen som reproduktionen av social klass. Andra delen i ledet är att undersöka hur dessa faktorer (som till exempel hälsa) själva hjälper till att förstärka reproduktionen. Angreppssättet kan bidra till en djupare förståelse för hur social klass påverkar och påverkas. Studien utgår från frågeställningen: Påverkar mäns psykiska och fysiska hälsa sambandet mellan deras sociala bakgrund och deras utbildningsnivå? Det empiriska material som används är delar ur Stockholm Birth Cohort, som bygger på såväl registerdata som surveyundersökningar. Materialet är baserat på personer som föddes 1953 och var mantalsskrivna i Stockholm den 1 november 1963. Urvalet omfattar 7305 individer och består endast av män. Vid analysen av resultaten presenteras deskriptiv information, en korrelationsmatris och en linjär regressionsanalys. I den senare av de tre studeras faderns inkomst, hälsa och den sociala klassens inverkan på utbildningsnivå och varandra. Resultaten i undersökningen visar att det finns ett starkt samband mellan social bakgrund och utbildningsnivå, vilket styrks av tidigare forskning. Förvånande är att resultaten som kopplas till hälsa går emot tidigare empiri. I denna studie återfinns ingen påverkan av hälsa på sambandet mellan social bakgrund och utbildningsnivå

Environmental factors more often is thought to have influence in determining children’s health and development. Prevalence of allergic diseases over the last decades is increasing, especially in Western Europe. Despite lots of performed surveys it is still unclear why the prevalence of food allergy is mounting. Incidence of food allergy is age dependent and usually manifest as one of the first forms of allergy. It is considered as the first step of „atopic march“. To accurately assess the occurrence of possible risk factors for a disease that can start already in infancy and may resolve by school age, a prospective birth cohort with regular follow-up of participating children and families provides the best possible study design. EuroPrevall birth cohort study, in which participated Vilnius University, was the first in the world investigation specially created just for evaluation of food allergy. During in this dissertation presented project for the first time real prevalence of food hypersensitivity and allergy in infants and small children in Lithuania have been determined, the most common food allergens were assessed and changes in prevalence of sensitization to them during first 30 months of life were analysed, also the role of possible determinants for the development of food allergies, such as genetic background, maternal diet during pregnancy and breastfeeding, way of birth, infections, medicines, psycho-social and environmental factors, were examined and different... [to full text] / Svarbus vaidmuo, nulemiantis vaikų sveikatą ir vystymąsi, vis dažniau priskiriamas vaiką supančiai aplinkai. Sergamumas alerginėmis ligomis sparčiai didėja, o pastaraisiais dešimtmečiais jis itin išaugo, ypač Vakarų Europoje. Nepaisant daugelio atliktų tyrimų, vis dar lieka neaišku, kodėl alerginių ligų paplitimas nuolat didėja. Alergijos maistui paplitimas įvairiose amžiaus grupėse skiriasi ir yra viena iš anksčiausiai pasireiškiančių alergijos formų. Manoma, kad ji gali būti pirmasis „atopinio maršo“ žingsnis. Norint tiksliai įvertinti galimų rizikos veiksnių įtaką ligos atsiradimui, kuri gali prasidėti jau kūdikystėje ir išnykti iki mokyklinio amžiaus, tinkamiausias tyrimo metodas yra prospektyvinis naujagimių kohortos tyrimas su reguliaria į tyrimą įtrauktų vaikų ir jų šeimų stebėsena. EuroPrevall naujagimių kohorta - tai pirmasis pasaulyje tyrimas, kuriame dalyvavo ir Vilniaus Universitetas, specialiai suformuotas tik alergijos maistui ištyrimui. Šio disertacijoje pateikiamo tyrimo metu Lietuvoje pirmąkart ištirtas padidėjusio jautrumo maistui ir alergijos maistui paplitimas tarp mažų vaikų ir nustatyti dažniausiai alergiją sukeliantys maisto produktai ir sensibilizacijos maisto alergenams kaita pirmaisiais 30 gyvenimo mėnesiais, taip pat išanalizuoti tėvų ir kūdikių rizikos veiksniai, tokie kaip genetinis pagrindas, mamos mityba nėštumo metu ir žindant, gimdymo būdas, infekcijos, vartoti medikamentai, psicho-socialiniai ir aplinkos faktoriai, įtakojantys alergijos... [toliau žr. visą tekstą]

Syftet med föreliggande kvantitativa studie är att undersöka sambandet mellan socioekonomisk klassposition i vuxenlivet och risken att vårdas för schizofreni. Sambandet mellan klassposition och hälsa kan ta sig uttryck i två riktningar - något som avhandlas i kausalitetsteorin och selektionsteorin. Kausalitetsteorin utgår från att en individs klassposition påverkar ens framtida hälsa, där en lägre klassposition riskerar att leda till sämre hälsa. I kontrast till detta utgår selektionsteorin från att en individs hälsa påverkar klasspositionen, där ohälsa tenderar att leda till en lägre klassposition. Dessa teorier utgör föreliggande studies teoretiska utgångspunkt. Datamaterialet som används är “Stockholm Birth Cohort” (SBC), vilket är resultatet av en sannolikhetsmatchning mellan två avidentifierade material. Materialet består av longitudinell kohortdata som sträcker sig från år 1953 till år 2008. Analysmetoden i föreliggande studie är multipel logistisk regressionsanalys vilket är lämpligt då utfallsvariabeln har gjorts binär. Resultatet som nås är att det existerar ett signifikant samband mellan socioekonomisk klassposition i vuxenlivet och risken att vårdas för schizofreni, även när sambandet kontrollerats för föräldrarnas socioekonomiska klassposition, psykiska hälsa, utbildning, inkomst, alkoholmissbruk samt familjetyp och kohortmedlemmens kön. Då denna infallsvinkel är relativt outforskad är detta resultat därför ett relevant bidrag till forskningsfältet. Vidare har försök gjorts att undersöka riktningen på detta samband och utifrån genomförda tester verkar det som att både kausalitets- och selektionsteorin har ett förklaringsvärde beroende på ifall klassposition mäts utifrån föräldrarnas eller individens klassposition. Rimligtvis är socioekonomisk klassposition och schizofreni ömsesidigt sammanlänkande över individens livsförlopp.

Background: Apart from individuals with clinical psychosis, community surveys have shown that many otherwise-well individuals endorse items designed to identify psychosis. The clinical relevance of psychotic-like experiences (PLE) in individuals who are not psychotic is not clear. This thesis aimed to examine the prevalence, demographic and psychosocial correlates and antecedents of PLE in the Australian community. Method: Data from three population-based studies was examined. The Australian National Survey of Mental Health and Wellbeing interviewed 10,641 individuals living in private dwellings in Australia. We examined the impact of selected demographic variables on endorsement of psychosis screen and probe items from the Composite International Diagnostic Interview (CIDI). We also examined the effect of exposure to traumatic events (with and without Post Traumatic Stress Disorder (PTSD)) on the endorsement of CIDI psychosis items. The youth component of the Australian National Survey of Mental Health and Wellbeing collected demographic and clinical data on a nationally representative sample of 1261 adolescents aged 13-17 years. The prevalence of hallucination endorsement on the Youth Self Report (YSR) in Australian adolescents was examined. The association between hallucination endorsement, demographic variables (sex, age, urbanicity and family composition) and clinical variables (self-reported depression, marijuana and alcohol use, DSM IV diagnoses, emotional/ behavioral problems as reported by the parent on the Child Behaviour Check List (CBCL)) were examined. The Mater- University of Queensland Study of Pregnancy (MUSP) is a prospective longitudinal birth cohort study of 7223 mothers and their offspring who received antenatal care between 1981 and 1984. Psychotic-like experiences were assessed in the offspring at the 21 year follow-up using the Peters Delusional Inventory (PDI) and the CIDI. We examined the prevalence of PLEs, and examined the effect of age (the age range at the 21 year follow-up was 18 to 23 years) and sex on PLE. A second study examined the emotional and behavioural antecedents of PLE at 21 years as measured by the CBCL at five and 14 years and the YSR at 14 years. Results: An estimated 11.7% of Australian adults endorsed at least one psychosisscreening item. Higher endorsement was associated with younger age, migrants from non- English speaking backgrounds, not being married, unemployment, living in an urban region and lowest socioeconomic levels. Exposure to any traumatic event was associated with increased endorsement of PLE (Rate Ratio =2.68; 95% CI 2.18, 3.30). A diagnosis of PTSD further increased endorsement of PLE (Rate Ratio =9.24; 95% CI 6.95, 12.27). Hallucinations were reported by 8.4% of Australian adolescents. Those living in blended or sole parent families were more likely to report hallucinations than those living with both biological parents (OR 3.27; 95% CI 1.93, 5.54; OR 2.60; 95% CI 1.63, 4.13 respectively). Hallucinations were more prevalent in adolescents who had high CBCL scores or elevated depression symptoms (OR 3.30; 95% CI 2.10, 5.20; OR 5.02; 95% CI 3.38, 7.45 respectively). Hallucinations were more prevalent in those adolescents who had smoked cannabis more than twice in the month prior to the survey (OR 3.27; 95% CI 1.76, 6.08). In the 21 year follow-up of the MUSP study, older age (18-20 compared to 21-23 years) was significantly associated with a reduction of CIDI delusions (OR 0.66, 95% CI 0.48, 0.92) and PDI total scores (OR=0.68, 95% CI 0.55, 0.83). Women were significantly more likely to endorse items related to hallucinations (OR=1.49, 95% CI 1.14, 1.95) but not delusions. High CBCL scores at 5 and 14 years predicted high total PDI scores; Those in the highest quartile of YSR scores at 14 years were nearly four times more likely to have high levels of psychotic-like experiences at age 21 (OR=3.71, 95% CI 2.92, 4.71). Adolescent onset psychopathology and continuous psychopathology through both childhood and adolescence strongly predict PLE at age 21. Conclusions: Psychotic-like experiences are relatively common in population surveys of Australian adults and adolescents. In adults, the demographic correlates of PLE are similar to those of schizophrenia. There is a strong association between PLE and exposure to trauma. The correlates of PLE in adolescents are different to those of adults. The reduction in prevalence of delusions between late adolescence and young adulthood is coincident with normal neurophysiological changes in the frontal lobes, suggesting hypotheses suitable for future research. The association between marijuana use and hallucinations in adolescents is further evidence of the potential harm caused by use of cannabis. The onset or persistence of emotional distress during adolescence is associated with an increased risk of PLE in adulthood. These findings are relevant to both clinical practice and future research. Psychotic symptoms create diagnostic uncertainty. There is potential for patients with anxiety (PTSD) or mood disorders to be incorrectly diagnosed with a psychotic illness and receive inappropriate management. Equally, there is a risk that subjects who have an emerging psychotic disorder and comorbid anxiety or depression or have had exposure to traumatic events may have treatment of their psychosis delayed as psychotic symptoms are incorrectly ascribed to a syndrome other than psychosis. Clinicians need to be aware of this diagnostic tension so that accurate assessments and appropriate treatments can be initiated at the earliest possible opportunity. The resolution of childhood emotional distress prior to adolescence appears to reduce the risk of PLE and possibly psychosis in adults. Strategies targeting emotionally distressed children may offer opportunities for psychosis prevention. Further research is required to explore the relationship between PLE and vulnerability to psychosis and other mental health problems. It remains unclear if PLE are reliable endophenotypes for schizophrenia. If this is the case, examining genetic and environmental risk factors for onset and persistence of PLE, and the neuroimaging changes that occur as individuals with PLE convert to psychosis will provide important new clues to our understanding of the aetiopathogenesis of psychosis.

Background. Despite extensive research the etiology of schizophrenia remains unclear. Whilst a substantial body of research points to a developmental component where early risk factors and maturational processes interact to culminate in psychosis during adulthood, key components and processes are yet to be confirmed. Prospective birth cohort studies, with their longitudinal data drawn from the general population, are vital to better understanding these pathways. To date, birth cohort (BC) studies have found that compared to healthy individuals, those who develop schizophrenia are more likely to display subtle deviations in certain developmental domains during infancy, childhood or adolescence. Yet there had been no recent review of these findings to identify areas of agreement, disagreement or where information was lacking. Aims. The overall aim of this dissertation is two-fold: firstly to identify and consolidate the current literature related to the antecedents of schizophrenia based on birth cohort studies; and secondly to undertake empirical studies based on an Australian birth cohort to address specific issues raised in the preceding review. Methods. The following three papers present empirical studies which use common methods based on an Australian birth cohort. Each study was based on a birth cohort of 3801 young adults born between 1981 and 1984, as part of the Mater University Study of Pregnancy and its outcomes. An extensive range of behavioural, cognitive, physical and social measures had been taken at various stages during their development namely, antenatally, at birth and six months, and at 5, 14 and 21 year follow-ups. Psychiatric diagnoses were obtained at age 21 follow-up from the Composite International Diagnostic Interview (CIDI), or, if this was not available, on a self-report health outcomes checklist; this produced the outcome variable ‘screen-positive non-affective psychosis’ (SP-NAP). The association between antecedents and later SP-NAP were examined using logistic regression adjusted for potentially confounding variables (such as actual age at assessment, cannabis use in adolescence, and gender). Each study also (a) examined differences in case vs. noncase maturation over time; and (b) conducted planned sensitivity and post hoc analyses, such as for source of diagnoses and predictive validity. Analyses were performed using SAS 9.2 (SAS). Results. The main findings of the review were that BC studies of schizophrenia provide important insights into both the maturational antecedents of schizophrenia and putative risk modifying factors. Yet while some antecedents, such as neurocognitive dysfunction, have been well documented, others are less certain (such as postnatal physical growth). There are no studies based on pre-morbid attentional measures. In addition, there were no studies of developmental pathways where continuity of maturation was based on within-individual scores rather than group means. These findings led to three empirical studies based on an Australian birth cohort previously untapped in psychosis research. The first study found that higher levels childhood and adolescent general psychopathology increased the risk of SP-NAP. This effect was less clear for females and when adolescent psychopathology had been rated by mothers at the 14-year follow-up. In contrast, self-reported hallucinations at the 14 year follow-up increased the risk of SP-NAP in both sexes. Males with high psychopathology scores in both childhood and adolescence were at greatest risk, followed by males and females whose ‘social, attention and thought’ scores were either consistently dysfunctional or worsened from childhood to adolescence (3- to 13-fold risk). The second study found that altered physical growth in infancy and adulthood (increased head circumference and height) raised the risk of SP-NAP for females but not males. For cases, there was no evidence of ‘catch-up growth’, i.e., growth retardation at birth being followed by a period of rapid growth. There was also no group difference in pubertal maturation for males or females. The final study found that dysfunction in childhood and adolescent intelligence, attention and speech increased the risk of SP-NAP for males but not females. Males with persistently high scores or who worsened on measures related to childhood and adolescent attentional problems were at greatest risk of SP-NAP. Discussion. While there are some caveats, disturbed developmental antecedents – particularly psychopathology and impaired cognition in males – were more frequently identified in cohort members who developed non-affective psychosis than their peers. More specifically, this disturbed development appeared be in domains which reflect those of the adult disorder and include the possible endophenotypes of psychosis-like experiences, inattention and visuospatial dysfunction. Of interest, self-rated items during adolescence were associated with increased risk of later psychosis. Finally, developmental pathways associated with non-affective psychosis were not uniform in timing but varied depending on such factors as domain and gender. These findings stress that understanding the heterogeneity in developmental pathways is crucial to understanding the heterogeneous nature of the subsequent disorder.