To coordinate visual perception and motor control in daily life where we are constantly surrounded by motion, we are dependent on normal visuomotor capacity. One essential prerequisite for normal visuomotor capacity is smooth pursuit eye movements (SP). Infants born very preterm (VPT = born <32 gestational weeks) are at high risk of developing disabilities in higher brain functions i.e. perception, cognition, concentration and coordination. In this thesis visuomotor capacity was investigated in a cohort of VPT infants (n = 113) and compared to control groups of full term (FT) infants. Levels of SP were measured at 2 and 4 months’ corrected age (CA). At 8 months’ CA reaching capacity toward a moving object was evaluated as this represents an executive activity guided by vision that develops at an early age. Lower levels of SP were found in the VPT infants compared to FT controls. The VPT boys showed higher levels of SP compared to the VPT girls. In VPT infants without major neonatal morbidities lower levels of SP was found compared to the FT controls. No difference in total capacity of gaze tracking was found, although the VPT infants lagged the object more at 4 months’ CA and used more saccades at 2 months’ CA. With age the VPT infants’ SP levels increased, but with a wider dispersion compared to the FT controls, and the levels of SP at 4 months’ CA corresponded to the levels of the FT infants at 2 months.  A number of perinatal risk factors were found to be negatively associated to lower levels of SP, and this effect was more pronounced in VPT infants with multiple risk factors,.  When evaluating the capacity to reach a moving object at 8 months’ CA, the VPT infants showed significantly more bimanual reach and more curved reaching paths to catch the object as compared to the FT control group. In conclusion, a delayed visuomotor capacity was found in VPT infants compared to FT control infants at 2, 4 and 8 months’ CA. Some VPT infants with perinatal risk factors did not develop in levels of SP between 2 and 4 months’ CA.

<p>The aim of the studies described in this thesis was to assess the association between certain perinatal factors and the risk of childhood lymphatic and myeloid leukemia and infant leukemia. </p><p>The five studies presented were all conducted in Sweden as population-based case-control studies. All cases were born and diagnosed between 1973-89 with leukemia up to the age of 16 years. A control was individually matched to each case. As Down’s syndrome entails a major risk for childhood leukemia, children with Down’s syndrome were excluded. The studies comprised a total of 652 cases, 47 of whom were diagnosed before the age of one year. Exposure data were extracted blindly from antenatal, obstetric, pediatric and other standardized medical records.</p><p>No association was found between prenatal exposure to ultrasound or diagnostic x-ray and childhood lymphatic or myeloid leukemia. Infant leukemia was associated with prenatal exposure to x-ray. A history of maternal lower genital tract infection significantly increased the risk of childhood leukemia, especially among children diagnosed at four years or older or in infancy. Factors such as young maternal age, and mothers working with children or in the health sector were associated with infant leukemia. Resuscitation with 100% oxygen with a face-mask and bag directly postpartum was associated with an increased risk of childhood lymphatic leukemia. The oxygen-related risk further increased if the manual ventilation lasted for three minutes or more. There was no association between lymphatic or infant leukemia and supplementary oxygen later in the neonatal period or other birth-related factors. Low Apgar scores at one and five minutes were associated with a non-significantly increased risk of lymphatic leukemia, and were significantly associated with infant leukemia.</p><p>Previously reported relations between childhood leukemia and exposures such as maternal diagnostic x-ray and birth related factors could not be confirmed by these studies. However, the present studies indicate that events during pregnancy or during the neonatal period are associated with increased risks of childhood and infant leukemia. These events can either be non-specific, such as exposure to maternal lower genital tract infection, or specific, such as the use of supplementary oxygen directly postpartum.</p>

The aim of the studies described in this thesis was to assess the association between certain perinatal factors and the risk of childhood lymphatic and myeloid leukemia and infant leukemia. The five studies presented were all conducted in Sweden as population-based case-control studies. All cases were born and diagnosed between 1973-89 with leukemia up to the age of 16 years. A control was individually matched to each case. As Down’s syndrome entails a major risk for childhood leukemia, children with Down’s syndrome were excluded. The studies comprised a total of 652 cases, 47 of whom were diagnosed before the age of one year. Exposure data were extracted blindly from antenatal, obstetric, pediatric and other standardized medical records. No association was found between prenatal exposure to ultrasound or diagnostic x-ray and childhood lymphatic or myeloid leukemia. Infant leukemia was associated with prenatal exposure to x-ray. A history of maternal lower genital tract infection significantly increased the risk of childhood leukemia, especially among children diagnosed at four years or older or in infancy. Factors such as young maternal age, and mothers working with children or in the health sector were associated with infant leukemia. Resuscitation with 100% oxygen with a face-mask and bag directly postpartum was associated with an increased risk of childhood lymphatic leukemia. The oxygen-related risk further increased if the manual ventilation lasted for three minutes or more. There was no association between lymphatic or infant leukemia and supplementary oxygen later in the neonatal period or other birth-related factors. Low Apgar scores at one and five minutes were associated with a non-significantly increased risk of lymphatic leukemia, and were significantly associated with infant leukemia. Previously reported relations between childhood leukemia and exposures such as maternal diagnostic x-ray and birth related factors could not be confirmed by these studies. However, the present studies indicate that events during pregnancy or during the neonatal period are associated with increased risks of childhood and infant leukemia. These events can either be non-specific, such as exposure to maternal lower genital tract infection, or specific, such as the use of supplementary oxygen directly postpartum.

Advancements in clinical care have led to a growing cohort of preterm-born individuals now entering adulthood. Before birth, such adults were often exposed to a suboptimal intrauterine environment, and after delivery, key developmental stages that would normally occur in utero during the third trimester had to take place under ex utero physiological conditions. Through detailed cardiovascular phenotyping, this thesis investigates the cardiovascular changes in preterm-born young adults, utilising a cohort of individuals with data collection since recruitment at birth. The detailed perinatal information was first used to design nested case-control studies to investigate the effects of early lipid and glucocorticoid exposure on long-term cardiovascular physiology in individuals born preterm. It was demonstrated that intravenous lipid administration leads to an artificial elevation of total cholesterol levels in immediate postnatal life, which is associated with long-term changes in aortic and left ventricular function proportional to the degree of cholesterol elevation. Additionally, exposure to antenatal glucocorticoids relates to a regional increase in aortic arch stiffness in young adulthood, as well as changes in glucose metabolism. It was then shown that young adults born preterm have increased left ventricular mass, out of proportion to blood pressure, and a unique three-dimensional left ventricular geometry, with reduced systolic and diastolic function compared to term-born controls. Similarly, they also show distinct differences in the right ventricle, with increased right ventricular mass and a proportion having clinically impaired right ventricular systolic function. Finally, it was demonstrated that preterm-born individuals have increased circulating levels of antiangiogenic factors in young adulthood, which relate to capillary rarefaction and blood pressure elevation. These findings are of considerable public health relevance given that nearly 10% of births are now preterm. Understanding whether modification of these variations in cardiovascular structure and function prevent the development of cardiovascular disease in this growing subgroup of the population will be of future interest.

Au cours des 30 dernières années, l’embonpoint et l’obésité infantile sont devenus de véritables défis pour la santé publique. Bien que l’obésité soit, à la base, un problème physiologique (i.e. balance calorique positive) une série de facteurs psychosociaux sont reliés à son développement. Dans cette thèse, nous avons étudié le rôle des facteurs périnataux et de la petite enfance dans le développement du surpoids, ainsi que la relation entre le surpoids et les troubles internalisés au cours de l’enfance et au début de l’adolescence. Nous avions trois objectifs généraux: 1) Modéliser le développement de l’indice de masse corporelle (IMC) ou du statut pondéral (le fait d’être en surpoids ou non) durant l’enfance, ainsi qu’estimer l’hétérogénéité dans la population au cours du temps (i.e. identification de trajectoires développementales de l’IMC). 2) Identifier les facteurs périnataux et de la petite enfance pouvant accroitre le risque qu’un enfant suive une trajectoire menant au surpoids adolescente. 3) Tester la possibilité que le surpoids durant l’enfance soit associé avec des problèmes de santé mentale internalisés à l’adolescence, et vérifier la possibilité qu’une telle association soit médiatisée par l’expérience de victimisation par les pairs et l’insatisfaction corporelle. Ce travail est mené dans une perspective de développement au cours de la vie (life span perspective), considérant l’accumulation des facteurs de risques au cours du temps ainsi que les facteurs qui se manifestent durant certaines périodes critiques de développement.1,2 Nous avons utilisé les données provenant de l’Étude Longitudinale du Développement des Enfants du Québec (ELDEQ), une cohorte de naissances de la province de Québec, Canada. L’échantillon initial était composé de 2120 familles avec un bébé de 5 mois nés au Québec en 1997. Ces familles ont été suivies annuellement ou à tous les deux ans jusqu’à ce que les enfants atteignent l’âge de 13 ans. En ce qui concerne le premier objectif de recherche, nous avons utilisé la méthode des trajectoires développementales fondée sur des groupes pour modéliser l’IMC en continu et en catégories (surpoids vs poids normal). Pour notre deuxième objectif, nous avons effectué des modèles de régression multinomiale afin d’identifier les facteurs périnataux et de la petite enfance associés aux différents groupes développementaux du statut pondéral. Les facteurs de risques putatifs ont été choisis parmi les facteurs identifiés dans la littérature et représentent l’environnement périnatal, les caractéristiques de l’enfant, ainsi que l’environnement familial. Ces facteurs ont été analysés longitudinalement dans la mesure du possible, et les facteurs pouvant servir de levier potentiel d’intervention, tels que l’usage de tabac chez la mère durant la grossesse, le sommeil de l’enfant ou le temps d’écoute de télévision, ont été sélectionnés pour l’analyse. Pour notre troisième objectif, nous avons examiné les associations longitudinales (de 6 à 12 ans) entre les scores-z d’IMC (selon la référence CDC 2000) et les problèmes internalisés avec les modèles d’équations structurales de type « cross-lagged ». Nous avons ensuite examiné comment la victimisation par les pairs et l’insatisfaction corporelle durant l’enfance peuvent médiatiser un lien potentiel entre le surpoids et les troubles internalisés au début de l’adolescence. Les contributions scientifiques de la présente thèse incluent l’identification de trajectoires distinctes du statut pondérale durant l’enfance (précoce, tardive, jamais en surpoids), ainsi que les facteurs de risques précoces et les profils de santé mentale pouvant différer selon la trajectoire d’un enfant. De plus, nous avons identifié des mécanismes importants qui expliquent une partie de l’association entre les trajectoires de surpoids et les troubles internalisés: la victimisation par les pairs et l’insatisfaction corporelle. / Child overweight and obesity has challenged the field of public health for several decades. While its direct underpinnings may be physiological, its development and outcome are intertwined with an array of psychosocial factors. This dissertation has sought to answer questions relating to the perinatal and early life risk factors associated with overweight development, as well as its potential psychological correlates during middle childhood and early adolescence. Specifically, this project had three research goals: 1) To model the developmental pattern of BMI or weight status throughout childhood and estimate population heterogeneity. 2) To identify the perinatal and early childhood risk factors that may increase the likelihood that a child follows a path leading to overweight by adolescence. 3) To examine whether being overweight in middle childhood is associated with internalizing mental health symptoms in early adolescence, and whether such an association is mediated by the experience of peer victimization and body dissatisfaction. This work takes a developmental life-course perspective in that it considers both the accumulation of risk factors over time as well as risk factors occurring during critical periods of development.1,2 We examined data drawn from the Quebec Longitudinal Study of Child Development (QLSCD), a population-based birth-cohort study in the province of Quebec, Canada. The initial sample consisted of 2120 families with a 5-month old baby born in Quebec in 1997. These families were monitored yearly or biennially until children were 13 years of age. For our first research goal, we modeled group-based developmental trajectories of child BMI and child weight status (overweight vs. not overweight). For our second goal, multinomial logistic regression analyses were conducted in order to identify the perinatal and early risk factors associated with the different developmental groups of weight status. Putative risk factors were chosen from the literature and represent the perinatal environment, child behavioral characteristics, as well as the family home environment. These were analyzed longitudinally when possible, and factors that could be targeted for intervention, such as maternal smoking during pregnancy, child sleep times or television viewing were selected for analysis. In order to complete our third research goal, we examined the longitudinal associations (from age 6 to 12) between BMI z-score (CDC 2000 reference) and internalizing and externalizing problems by way of cross-lag panel models in the Mplus program. Our results indicating sparse cross-lagged links, we then examined whether peer victimization and body dissatisfaction during childhood mediate the association between early overweight development and self-reported internalizing symptoms in early adolescence. Important scientific contributions stemming from this project include the identification of distinct weight status trajectories during childhood (i.e. early onset, late onset, never overweight) and the identification of perinatal and early life risk factors and mental health outcomes that may differ depending on a child’s developmental trajectory. Additionally, we identified two important mechanisms of the association between overweight and internalizing problems: peer victimization and low body satisfaction.