Exposure cigarette smoke (CS) during prenatal life is the leading cause of preventable premature death. In this study, we explored the hypothesis that in vitro exposure of fetal lung cells to cigarette smoke extract (CSE) may result in the alteration of apoptosis through activation of caspase-3. Alongside we compared the responses of fetal lung cells with A549 cells and rat periodontal ligament (PDL) fibroblasts exposed to CSE in a dose dependent manner. Caspase-3 activity and inhibition was measured using a fluorometric assay. Cell viability in smoke exposed cells was measured using MTT formazan assay. Caspase-3 expression and cellular localization was detected by western blot analysis and immunofluorescence. Our results indicate that caspase-3 activity was significantly (p < 0.05) elevated and cell viability was significantly inhibited in fetal rat lung cells exposed to 10% or 15 % (v/v) CSE. No significant differences were observed in the caspase-3 activity or cellular viability in A549 cells and rat PDL fibroblasts exposed to 5%, 10% or 15% (v/v) CSE. Activation of caspase-3 in fetal lung connective tissue and alveolar epithelial cells may be one of the reasons for the developmental pulmonary toxicity induced by CSE.

[Truncated abstract] With the dramatic rise in asthma and allergic disease there is an urgent need to define the early life exposures which influence developing immune responses to increase the predisposition to allergic disease. While this is clearly multifactorial, this thesis addresses the effects of maternal smoking as a major adverse, yet avoidable exposure in early life. I hypothesised that the well-documented increased susceptibility to infection in infants of smokers could indicate underlying effects on innate Toll-like receptor (TLR) mediated microbial responses which could in turn contribute to early immune dysregulation and increased risk of allergic disease. In addition to providing the first defence against microbes, TLR-mediated pathways modulate subsequent specific immune response and are of growing interest in the potential inhibition of inappropriate allergic responses. My initial interest in the potential immune effects of smoking in pregnancy was based on preliminary retrospective analyses of a previous cohort (presented in Chapter 3) which suggested possible effects on T cell cytokine responses to mitogens and allergens. Based on this, I recruited a new prospective pregnancy cohort (n=122) of smokers (n=60) and non-smokers (n=62) (as outlined in Chapter 4) to confirm this and test my novel hypothesis that maternal smoking may be affecting important innate (TLR-mediated) immune pathways. … Thus, these findings could indicate that smoking increases the early susceptibility to infection thereby increasing subsequent IgA responses. This is supported by observations that key neonatal TLR responses are attenuated in children who go onto develop wheezy illnesses and lower respiratory tract infections. Together, the study findings suggest that in addition to effects on lung growth, maternal smoking may also influence aspects of neonatal innate immune function that are now believed to play a critical role in microbial-driven postnatal immune development, highlighting that other environmental interactions are also highly relevant to the v

Abstract The prevalence of overweight and obesity among adolescents has increased worldwide at the population-level, reflecting inactive lifestyle and excessive energy intake. The comorbidities of obesity, e.g. impaired glucose tolerance and high blood pressure increase the risk for cardiovascular diseases. The first manifestation of cardiovascular diseases can be detected in young adulthood, and prevention should be focused to those at highest risk. This study was aimed to evaluate the changes in body weight and body composition, physical fitness and cardiometabolic risk factors, associated with physical exercise during military service. Furthermore, this study investigated the association of antenatal and lifestyle factors with the body composition and physical fitness among young men. The material of this study consisted of 1046 men (mean age 19.2 years) who began their compulsory military service in the Sodankylä Jaeger Brigade in 2005. The conscripts’ cardiometabolic risk factors, body weight, body composition, fitness, and lifestyle habits were evaluated at baseline and after 6–12 months military service. The data on the participants’ mothers’ antenatal and participants’ childhood period was available for 508 offsprings, who belonged to the 1986 Northern Finland Birth Cohort. During the military service the prevalence of metabolic syndrome decreased in the overall cohort from 6.1% to 3.6%, and the reduction was present among overweight and obese conscripts. The reduction in metabolic syndrome was associated with the reduction in waist circumference, weight loss and improvement in muscle fitness. Some lifestyle factors e.g. maternal smoking during pregnancy and conscripts’ smoking, alcohol consumption and binge drinking were associated with the conscripts’ body composition and fitness test results. Military service was especially beneficial for those reporting weekly binge drinking, who showed the greatest reduction in body weight and fat, and improvements in physical fitness and lifestyle habits. This study shows that unbeneficial lifestyle habits can be seen as detrimental to the body composition and fitness levels of young men. Furthermore, the physical exercise is in important role for reducing the metabolic syndrome, already present in young men. Maternal smoking during pregnancy was associated with reduced aerobic fitness in the subjects, underlining its long-standing consequences on offspring’s health. / Tiivistelmä Väestötutkimusten perusteella nuorten ylipaino ja lihavuus ovat yleistyneet, liittyen inaktiiviseen elämäntapaan ja liialliseen energiansaantiin. Lihavuuden liitännäissairaudet, kuten heikentynyt sokerinsieto ja kohonnut verenpaine lisäävät riskiä sydän- ja verisuonisairauksille. Sydän- ja verisuonisairauksien ensimmäiset ilmentymät voidaan havaita nuorella aikuisiällä ja sairauden ehkäisystrategiat tulisi kohdentaa riskiryhmiin. Tässä tutkimuksessa arvioitiin varusmiespalvelukseen liittyvän liikunnan aikaansaamia muutoksia kehonpainossa, kehonkoostumuksessa, fyysisessä kunnossa sekä sydän- ja verisuonisairauksien riskitekijöissä. Lisäksi tutkimus arvioi äidin raskausaikaan liittyvien tekijöiden ja elintapojen yhteyttä nuorten miesten kehonkoostumukseen ja fyysiseen kuntoon. Tutkimusaineisto koostui 1046 miehestä (keski-ikä 19.2 vuotta), jotka astuivat varusmiespalvelukseen Sodankylän Jääkäriprikaatissa vuonna 2005. Varusmiesten sydän- ja verisuonisairauksien riskitekijät, kehonpaino, kehonkoostumus, kunto ja elintavat arvioitiin palveluksen alussa ja lopussa (seuranta-aika 6–12 kk). Varusmiesten äitien raskaudenaikaiset ja varusmiesten varhaislapsuuden tiedot olivat käytettävissä 508:lta tutkittavalta, jotka kuuluivat Pohjois-Suomen syntymäkohorttiin 1986. Varusmiespalveluksen aikana metabolisen oireyhtymän vallitsevuus väheni koko aineistossa 6.1 %:sta 3.6 %:iin, ja väheneminen oli havaittavissa ylipainoisten ja lihavien joukossa. Metabolisen oireyhtymän väheneminen oli yhteydessä vyötärönympäryksen ja painon laskuun sekä lihaskunnon paranemiseen. Elintavat, kuten äidin raskaudenaikainen tupakointi ja varusmiehen ruokavalio, tupakointi, alkoholin kulutus ja humalahakuinen juominen olivat yhteydessä varusmiehen kehonkoostumukseen ja fyysiseen kuntoon. Varusmiespalveluksesta hyötyivät erityisesti ne, jotka raportoivat viikoittaista humalahakuista juomista; heillä havaittiin myönteisiä muutoksia kehonkoostumuksessa, fyysisessä kunnossa ja elintavoissa. Tämän tutkimuksen perusteella voidaan myös todeta, että äidin raskaudenaikainen tupakointi vaikuttaa jälkeläisen heikompaan aerobiseen kuntoon. Tutkimus osoittaa epäterveellisten elämäntapojen vaikutukset epäedulliseen kehonkoostumukseen ja heikompaan fyysiseen kuntoon nuorilla miehillä. Lisäksi liikunnan merkitys nuorten miesten sydän- ja verisuonisairauksien riskitekjöiden hoidossa on oleellista.

Despite advances in health promotion through efforts to reduce tobacco smoking, tobacco-related health conditions have continued to be significant. Exposure to secondhand smoke has been identified as a health risk also in addition to infant health risks related to maternal smoking. In contrast, breastfeeding has been found to promote infant health and is strongly encouraged. Despite literature supporting both of these statements, the combined effects of both breastfeeding and maternal smoking on infant wellbeing have not been delineated. Otitis media represents a common health problem among infants and young children. Tobacco exposure has been shown to increase its incidence while breastfeeding has been shown to reduce its occurrence. In the current study, a consecutive sample of all infants less than 5 years of age with otitis media and breastfed for at least 6 months was collected from a busy urban clinic for analysis. A survey tool was administered to those meeting study criteria. Primary analysis examined the odds ratio of developing otitis media among breastfed infants between those whose mothers smoked tobacco and those whose mothers did not. As a result, the association between the protective effects of breastfeeding and the detrimental effects of maternal smoking was evaluated in relation to the development of otitis media. Secondary variables including demographics, family history, past medical and birth history, and secondhand smoke exposure were also assessed. Results failed to demonstrate a significant difference in otitis media between the 2 cohorts in this study, and of the secondary variables, only cranio-facial deformities and/or a family history of these conditions resulted in higher otitis media occurrence. Further study with larger populations with higher tobacco use rates may offer additional insights into this matter.

No description available.

Trajectoires développementales de l’IMC durant l’enfance: Une étude longitudinale sur 8 ans. Introduction : L’obésité infantile, origine de nombreux problèmes de santé, représente un grand défi en santé publique. Récemment, l’importance d’étudier l’évolution du surpoids durant l’enfance ainsi que les facteurs de risques précoces pour l’obésité a été reconnue. Les trajectoires développementales d’indice de masse corporelle (IMC) chez les jeunes représentent une approche innovatrice qui nous permet de mieux comprendre cette problématique importante. Objectifs: 1) Identifier des trajectoires développementales distinctes de groupes d’enfants selon leur IMC durant l’enfance, et 2) Explorer les facteurs de risques précoces qui prédisent l’appartenance de l’enfant à la trajectoire d’IMC le plus élevé Hypothèses: 1) On s’attend à retrouver un groupe d’enfants qui suit une trajectoire d’IMC élevée durant l’enfance. 2) On s’attend à ce que certaines caractéristiques de la mère (ex : tabac pendant la grossesse et IMC élevé), soient associées à l’appartenance de l’enfant au groupe ayant la trajectoire «IMC élevé ». Méthodes: Estimation des trajectoires développementales d’IMC d’enfants, dans un échantillon populationnel (n=1957) au Québec (ELDEQ). Les IMC ont été calculés à partir de données fournies par les mères des enfants et recueillis chaque année sur une durée de 8 ans. Des données propres à l’enfant sa mère, ainsi que socioéconomiques, ont étés recueillies. Une régression logistique multinomiale a été utilisée pour distinguer les enfants avec un IMC élevé des autres enfants, selon les facteurs de risques précoces. Les programmes PROC TRAJ (extension de SAS), SPSS (version 16), et SAS (version 9.1.3) ont été utilisés pour ces analyses. Résultats: Trois trajectoires d’IMC ont étés identifiées : IMC « bas-stable » (54,5%), IMC « modéré » (41,0%) et IMC « élevé et en hausse » (4,5%). Le groupe « élevé et en hausse » incluait des enfants pour qui l’IMC à 8 ans dépassait la valeur limite pour l’obésité. Les analyses de régression logistique ont révélé que deux facteurs de risques maternels étaient significativement associés avec la trajectoire “en hausse” par rapport aux deux autres groupes : le tabac durant la grossesse et le surpoids maternel. Conclusions: Des risques d’obésité infantile peuvent êtres identifiés dès la grossesse. Des études d’intervention sont requises pour identifier la possibilité de réduire le risque d’obésité chez l’enfant en ciblant le tabac et le surpoids maternelle durant la grossesse. Mots clés: Indice de masse corporelle (IMC), obésité infantile, trajectoires développementales de groupe, facteurs de risque précoce, étude populationnelle, tabac pendant la grossesse, obésité maternelle. / Developmental Trajectories of Body Mass Index in Early Childhood: An 8-Year Longitudinal Study. Introduction: Childhood obesity has become one of the greatest Public Health challenges this century, affecting not only developed nations, but increasingly low- and middle-income countries as well. Estimating developmental trajectories of Body Mass Index (BMI) during early childhood represents an innovative approach towards a better understanding of the development of this health problem. Objective: To identify groups of children with distinct developmental trajectories of Body Mass Index (BMI) between the ages of five months and eight years, and to identify early-life risk factors that distinguish children in an atypically elevated BMI trajectory group. Methods: Group-based developmental trajectories of BMI were estimated from annual maternal assessments (5 months to 8 years) in a large population sample (n=1957). Measures of height and weight, as well as family and child characteristics were obtained yearly from mothers. Multivariate logistic regression was used to distinguish children with elevated BMI from other children, using pre and early post-natal risk factors. Results: Three trajectories of BMI were identified: low-stable BMI (54.5%), moderate BMI (41.0%) and high-rising BMI (4.5%). The high-rising group included children whose BMI, at eight years of age, exceeded the cut-off value for obesity. Multinomial logit regression analyses revealed that two maternal risk factors were significantly associated with the high-rising BMI trajectory group as compared to both the low and moderate groups: smoking during pregnancy and maternal overweight. Conclusions: Antecedents of childhood obesity can be identified during pregnancy. Intervention studies are needed in order to test the possibility that targeting maternal smoking and maternal obesity during pregnancy would reduce the risk of childhood obesity in the offspring. Keywords: Body Mass Index (BMI), child obesity, Group-based developmental trajectories, early life predictors, population-based study, maternal smoking, maternal obesity.

Antecedents: No hi ha gaire coneixement sobre el neurodesenvolupament de preescolars i la seva susceptibilitat enfront a factors ambientals. Objectius: Avaluar les respostes del neurodesenvolupament en nens i les seves característiques psicomètriques, i, si factors ambientals primerencs (ex., duració de la lactància materna i mares que fumen) poden influir tals respostes. Mètodes: Dues cohorts prospectives des del naixement en població general (Menorca (N=421) i Ribera d'Ebre (N=79)) van se seguides fins als 4 anys d'edat durant un període de dos anys (2001-2003). Els nens van ser avaluats per tres psicòlegs i els seus respectius mestres per les funcions neuropsicològiques (MCSA), els comportaments de dèficit d'atenció i d'hiperactivitat (TDAH-DSM-IV) i la competència social (CPSCS); junt amb l'administració (en persona) a les mares de qüestionaris generals.Resultats: Les respostes van mostrar característiques psicomètriques acceptables i els patrons neuropsicològics del TDAH eren consistents amb altres troballes sobre TDAH. La lactància materna de llarga durada estava associada amb una millora de totes les àrees comportamentals avaluades. Fumar durant l'embaràs estava associat a puntuacions cognitives més baixes.Conclusions: Avaluar el neurodesenvolupament a preescolars sans és factible i necessari per investigar efectes primerencs de factors ambientals i aplicar polítiques preventives de salut pública. / Background: Little is known about neurodevelopment among preschoolers and its susceptibility to environmental factors.Objectives: Assess neurodevelopmental outcomes and their psychometric characteristics in children; and, if early environmental factors (i.e., duration of breastfeeding and maternal smoking) influence the neurobehavioral outcomes. Methods: Two prospective population-based birth cohorts (Menorca (N=421) and Ribera d'Ebre county (N=79)) were followed up at the age of 4 years during a two year period (2001-2003). Children were assessed by three psychologists and their respective teachers for neuropsychological functions (MCSA), inattention-hyperactivity behaviors (ADHD-DSM-IV) and social behavior (CPSCS); in addition to maternal in person general questionnaires. Results: Outcomes showed acceptable psychometric characteristics and ADHD neuropsychological patterns were consistent with other ADHD findings. Long-term breastfeeding was associated with the improvement of all behavioral areas assessed. Maternal smoking during pregnancy was associated with lower cognitive scores.Conclusions: Assessing neurodevelopment in healthy preschoolers is feasible and necessary to investigate early effects of environmental factors and apply public health preventive policies.

Trajectoires développementales de l’IMC durant l’enfance: Une étude longitudinale sur 8 ans. Introduction : L’obésité infantile, origine de nombreux problèmes de santé, représente un grand défi en santé publique. Récemment, l’importance d’étudier l’évolution du surpoids durant l’enfance ainsi que les facteurs de risques précoces pour l’obésité a été reconnue. Les trajectoires développementales d’indice de masse corporelle (IMC) chez les jeunes représentent une approche innovatrice qui nous permet de mieux comprendre cette problématique importante. Objectifs: 1) Identifier des trajectoires développementales distinctes de groupes d’enfants selon leur IMC durant l’enfance, et 2) Explorer les facteurs de risques précoces qui prédisent l’appartenance de l’enfant à la trajectoire d’IMC le plus élevé Hypothèses: 1) On s’attend à retrouver un groupe d’enfants qui suit une trajectoire d’IMC élevée durant l’enfance. 2) On s’attend à ce que certaines caractéristiques de la mère (ex : tabac pendant la grossesse et IMC élevé), soient associées à l’appartenance de l’enfant au groupe ayant la trajectoire «IMC élevé ». Méthodes: Estimation des trajectoires développementales d’IMC d’enfants, dans un échantillon populationnel (n=1957) au Québec (ELDEQ). Les IMC ont été calculés à partir de données fournies par les mères des enfants et recueillis chaque année sur une durée de 8 ans. Des données propres à l’enfant sa mère, ainsi que socioéconomiques, ont étés recueillies. Une régression logistique multinomiale a été utilisée pour distinguer les enfants avec un IMC élevé des autres enfants, selon les facteurs de risques précoces. Les programmes PROC TRAJ (extension de SAS), SPSS (version 16), et SAS (version 9.1.3) ont été utilisés pour ces analyses. Résultats: Trois trajectoires d’IMC ont étés identifiées : IMC « bas-stable » (54,5%), IMC « modéré » (41,0%) et IMC « élevé et en hausse » (4,5%). Le groupe « élevé et en hausse » incluait des enfants pour qui l’IMC à 8 ans dépassait la valeur limite pour l’obésité. Les analyses de régression logistique ont révélé que deux facteurs de risques maternels étaient significativement associés avec la trajectoire “en hausse” par rapport aux deux autres groupes : le tabac durant la grossesse et le surpoids maternel. Conclusions: Des risques d’obésité infantile peuvent êtres identifiés dès la grossesse. Des études d’intervention sont requises pour identifier la possibilité de réduire le risque d’obésité chez l’enfant en ciblant le tabac et le surpoids maternelle durant la grossesse. Mots clés: Indice de masse corporelle (IMC), obésité infantile, trajectoires développementales de groupe, facteurs de risque précoce, étude populationnelle, tabac pendant la grossesse, obésité maternelle. / Developmental Trajectories of Body Mass Index in Early Childhood: An 8-Year Longitudinal Study. Introduction: Childhood obesity has become one of the greatest Public Health challenges this century, affecting not only developed nations, but increasingly low- and middle-income countries as well. Estimating developmental trajectories of Body Mass Index (BMI) during early childhood represents an innovative approach towards a better understanding of the development of this health problem. Objective: To identify groups of children with distinct developmental trajectories of Body Mass Index (BMI) between the ages of five months and eight years, and to identify early-life risk factors that distinguish children in an atypically elevated BMI trajectory group. Methods: Group-based developmental trajectories of BMI were estimated from annual maternal assessments (5 months to 8 years) in a large population sample (n=1957). Measures of height and weight, as well as family and child characteristics were obtained yearly from mothers. Multivariate logistic regression was used to distinguish children with elevated BMI from other children, using pre and early post-natal risk factors. Results: Three trajectories of BMI were identified: low-stable BMI (54.5%), moderate BMI (41.0%) and high-rising BMI (4.5%). The high-rising group included children whose BMI, at eight years of age, exceeded the cut-off value for obesity. Multinomial logit regression analyses revealed that two maternal risk factors were significantly associated with the high-rising BMI trajectory group as compared to both the low and moderate groups: smoking during pregnancy and maternal overweight. Conclusions: Antecedents of childhood obesity can be identified during pregnancy. Intervention studies are needed in order to test the possibility that targeting maternal smoking and maternal obesity during pregnancy would reduce the risk of childhood obesity in the offspring. Keywords: Body Mass Index (BMI), child obesity, Group-based developmental trajectories, early life predictors, population-based study, maternal smoking, maternal obesity.

Abstract A low level of physical activity and poor physical fitness are important risk factors of chronic non-communicable diseases and all-cause mortality. Much of the risk of these diseases originates in fetal life. The associations of early-life determinants with physical activity and fitness later in life are as yet not well studied. The aim of this work was to investigate early-life factors as predictors of physical activity and fitness in adolescence and young adulthood. We assessed a wide range of parental and pregnancy-related factors in 16-year-old adolescent participants of the Northern Finland Birth Cohort 1986 (n=7,344), and focused on the long-term consequences of preterm birth in the 23-year-old adult participants of the ESTER study (n=1,161). Prenatal and parental predictors of low physical activity and cardiorespiratory fitness in adolescence included high gestational age-related birth weight as well as parental overweight or obesity. Also, both short and long gestational lengths were associated with lower physical activity, and maternal gestational diabetes mellitus and smoking during pregnancy were associated with lower cardiorespiratory fitness. Young adults born before 34 weeks of gestation reported substantially less leisure-time physical activity than those born at term, although this was not detected by accelerometer measurement. Those born preterm had lower muscular fitness, as individuals born before 37 weeks were able to perform fewer modified push-ups, and those born before 34 weeks had lower handgrip strength, but no difference was observed in cardiorespiratory fitness. Based on questionnaire data, young adults born before 34 weeks perceived themselves to be less fit than their term-born peers. Most individuals exposed to preterm birth or maternal gestational disorders are relatively healthy when reaching adulthood. However, their lower levels of physical activity and physical fitness compared with their peers born at term may contribute to a higher risk of chronic non-communicable diseases in later life. Finding physical activities that are suitable for each individual is essential to promote well-being and health and diminish the increased disease risk later in life. / Tiivistelmä Vähäinen fyysinen aktiivisuus ja heikko fyysinen kunto ovat merkittäviä kroonisten sairauksien ja ennenaikaisen kuoleman riskitekijöitä. Jo sikiökautisten tekijöiden tiedetään vaikuttavan syntyvän lapsen kroonisten sairauksien riskiin myöhemmin elämässä, mutta elämän varhaisvaiheen tekijöiden yhteyttä myöhempään fyysiseen aktiivisuuteen ja kuntoon on tutkittu verrattain vähän. Väitöstutkimuksen tavoitteena oli selvittää elämän varhaisvaiheen tekijöiden yhteyttä fyysiseen aktiivisuuteen ja kuntoon nuoruusiässä ja nuorena aikuisena. Tarkastelimme useiden vanhempiin ja raskausaikaan liittyvien tekijöiden vaikutuksia Pohjois-Suomen syntymäkohortti 1986 16-vuotistutkimuksessa (n=7344) ja keskityimme ennenaikaisen syntymän pitkäaikaisvaikutuksiin ESTER-tutkimuksen 23-vuotiaiden nuorten aikuisten aineistossa (n=1161). Tutkimustulostemme mukaan raskauden kestoon suhteutettu suuri syntymäpaino sekä vanhempien ylipaino tai lihavuus ennustivat vähäisempää liikunta-aktiivisuutta ja heikompaa kestävyyskuntoa nuoruusiässä. Sekä keskimääräistä lyhyempi että pidempi raskaudenkesto olivat yhteydessä vähäisempään liikunta-aktiivisuuteen ja äidin raskausdiabetes ja tupakointi raskauden aikana puolestaan heikompaan kestävyyskuntoon. Alle 34-viikkoisena syntyneet raportoivat liikkuvansa nuorena aikuisena vapaa-aikanaan huomattavasti vähemmän kuin täysiaikaisena syntyneet, vaikka eroa ei kiihtyvyysantureilla mitattuna fyysisessä aktiivisuudessa havaittukaan. Verrattuna täysiaikaisena syntyneisiin, ennenaikaisesti syntyneillä aikuisilla oli heikompi lihaskunto etunojapunnerrustestillä mitattuna ja hyvin ennenaikaisesti syntyneillä käden puristusvoima oli heikompi. Kestävyyskunnossa ei havaittu eroja. Hyvin ennenaikaisesti syntyneet myös arvioivat fyysisen kuntonsa huonommaksi kuin täysiaikaisena syntyneet ikätoverinsa. Vaikka valtaosa ennenaikaisena syntyneistä ja äidin raskaudenaikaisille sairauksille altistuneista on aikuisena varsin terveitä, liikunnan vähäisyys ja heikko fyysinen kunto voivat lisätä kroonisten sairauksien riskiä myöhemmin elämässä. Siksi tähän ryhmään kuuluvia tulisi erityisesti auttaa löytämään itselleen sopivia liikuntamuotoja hyvinvoinnin ja terveyden edistämiseksi ja siten myöhempien sairauksien ennaltaehkäisemiseksi.