京都大学 / 新制・課程博士 / 博士(医学) / 甲第24132号 / 医博第4872号 / 新制||医||1059(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 湊谷 謙司, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Regular physical activity during pregnancy provides both maternal and infant health benefits. The complexity of measuring physical activity during pregnancy hampers the determination of the optimal dose of habitual physical activity for pregnant women and has led to broad physical activity guidelines for pregnant women. Subjectively-determined physical activity levels by means of questionnaires may have contributed to these broad guidelines. However the ActiHeart®, a dual heart rate monitor and accelerometer, is an accurate and reliable measurement tool to determine physical activity levels during pregnancy. Maternal physical activity tends to decrease during pregnancy and may lead to various health risks, including excessive weight gain, risk for gestational diabetes, lower back pain and adverse foetal outcomes. Determining the influence of physical activity on foetal growth is confounded by various variables, therefore objectively-measured habitual physical activity is essential. This study aims to objectively determine habitual physical activity patterns of pregnant women and the relationship between habitual physical activity and foetal growth parameters. In a longitudinal, observational, cohort study design, 60 pregnant women were measured at four stages in their pregnancy: the first trimester (9 – 12 weeks), second trimester (20 – 22 weeks), third trimester (28 – 32 weeks) and three months postpartum. Demographic information was collected by means of a questionnaire specifically compiled for this study, followed by anthropometric measurements (height and weight). Assessment of the participants resting blood pressure, heart rate (Microlife® Semi-Automatic blood pressure and heart rate monitor) and metabolic rate (FitmateTM, Cosmed) was obtained. Thereafter, a step-test was performed for individualised calibration of the ActiHeart® device for assessment of habitual physical activity patterns over a 7-day period. Foetal growth parameters that included birth weight (kg), birth length (cm), abdominal circumference (cm) and head circumference (cm), were collected from medical records and from the mother post-partum. Habitual physical activity, presented as average Activity Energy Expenditure (AEE), physical Activity Level (PAL), activity counts and minutes spent in activity, declined from the first to the third trimester of pregnancy. The AEE during the first trimester averaged 803 ± 34 kCal/day and declined statistically significant to 592 ± 383 kCal/day in the third trimester. Minutes spent per week doing moderate activity declined from 103 ± 83 min/week in the first trimester to 55 ± 66 min/week in the third trimester. Average pregnancy AEE indicated a non-significant negative relationship with all foetal growth measurements - birth weight (r = - 0.39, p = 0.45), birth length (r = - 0.16, p = 0.77), Ponderal Index (r = - 0.34, p = 0.51) - and a non-significant positive relationship with head circumference at birth (r = 0.14, p = 0.79). In conclusion, the objectively-determined, habitual physical activity levels of the participants did not meet the stated guidelines for pregnant women. During the progression of pregnancy, the activity levels declined significantly at the third trimester. The habitual activity levels indicate no effect on the foetal growth parameters. / MSc (Biokinetics), North-West University, Potchefstroom Campus, 2014

Regular physical activity during pregnancy provides both maternal and infant health benefits. The complexity of measuring physical activity during pregnancy hampers the determination of the optimal dose of habitual physical activity for pregnant women and has led to broad physical activity guidelines for pregnant women. Subjectively-determined physical activity levels by means of questionnaires may have contributed to these broad guidelines. However the ActiHeart®, a dual heart rate monitor and accelerometer, is an accurate and reliable measurement tool to determine physical activity levels during pregnancy. Maternal physical activity tends to decrease during pregnancy and may lead to various health risks, including excessive weight gain, risk for gestational diabetes, lower back pain and adverse foetal outcomes. Determining the influence of physical activity on foetal growth is confounded by various variables, therefore objectively-measured habitual physical activity is essential. This study aims to objectively determine habitual physical activity patterns of pregnant women and the relationship between habitual physical activity and foetal growth parameters. In a longitudinal, observational, cohort study design, 60 pregnant women were measured at four stages in their pregnancy: the first trimester (9 – 12 weeks), second trimester (20 – 22 weeks), third trimester (28 – 32 weeks) and three months postpartum. Demographic information was collected by means of a questionnaire specifically compiled for this study, followed by anthropometric measurements (height and weight). Assessment of the participants resting blood pressure, heart rate (Microlife® Semi-Automatic blood pressure and heart rate monitor) and metabolic rate (FitmateTM, Cosmed) was obtained. Thereafter, a step-test was performed for individualised calibration of the ActiHeart® device for assessment of habitual physical activity patterns over a 7-day period. Foetal growth parameters that included birth weight (kg), birth length (cm), abdominal circumference (cm) and head circumference (cm), were collected from medical records and from the mother post-partum. Habitual physical activity, presented as average Activity Energy Expenditure (AEE), physical Activity Level (PAL), activity counts and minutes spent in activity, declined from the first to the third trimester of pregnancy. The AEE during the first trimester averaged 803 ± 34 kCal/day and declined statistically significant to 592 ± 383 kCal/day in the third trimester. Minutes spent per week doing moderate activity declined from 103 ± 83 min/week in the first trimester to 55 ± 66 min/week in the third trimester. Average pregnancy AEE indicated a non-significant negative relationship with all foetal growth measurements - birth weight (r = - 0.39, p = 0.45), birth length (r = - 0.16, p = 0.77), Ponderal Index (r = - 0.34, p = 0.51) - and a non-significant positive relationship with head circumference at birth (r = 0.14, p = 0.79). In conclusion, the objectively-determined, habitual physical activity levels of the participants did not meet the stated guidelines for pregnant women. During the progression of pregnancy, the activity levels declined significantly at the third trimester. The habitual activity levels indicate no effect on the foetal growth parameters. / MSc (Biokinetics), North-West University, Potchefstroom Campus, 2014

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Résumé: Le surpoids et l’obésité dans la population pédiatrique sont des préoccupations grandissantes à l’échelle mondiale. Actuellement, au Canada, près de 21 % des jeunes Canadiens âgés de 2 à 5 ans présentent un surpoids et malheureusement, 6 % d’entre eux souffrent d’obésité. De plus, 80 % de ces enfants risquent d’être obèses à l’âge adulte, ce qui mène à plusieurs impacts sur la santé. Afin de prévenir l’obésité infantile, il est important d’identifier des facteurs de risques, notamment ceux se produisant tôt dans la vie. Plusieurs études ont démontré l’importance de l’environnement fœtal dans l’établissement de la santé métabolique à long terme. Le poids à la naissance a souvent été utilisé comme marqueur de l’exposition prénatale. Cependant, le poids à la naissance n’est qu’un marqueur grossier. L’adiposité à la naissance a été identifiée comme un facteur de risque plus important puisqu’elle permet de prédire de l’adiposité durant l’enfance. Les deux déterminants maternels majeurs de la croissance fœtale sont le statut pondéral et la glycémie maternelle. Récemment, une adipokine a été suggérée comme un déterminant potentiel dans la programmation fœtale de l’obésité. La leptine, qui est produite par les adipocytes, joue un rôle important dans la balance énergétique, mais elle semble aussi importante dans le développement de l’obésité postnatale. Durant la grossesse, le placenta produit une large quantité de leptine et la majorité est sécrétée du côté maternel. Appuyés par le fait que la leptine maternelle circulante est le reflet de la sécrétion placentaire de leptine, nous avons émis l’hypothèse que la leptine maternelle serait associée à l’adiposité du nouveau-né, et ce, indépendamment de la glycémie maternelle. Nous avons étudié la leptine durant l’hyperglycémie provoquée par voie orale (HGPO) chez les femmes enceintes au 2e trimestre. Nous avons montré, chez les femmes en surpoids ou obèse, qu’une plus haute leptine maternelle était lié à une adiposité néonatale augmentée à la naissance. D’un autre côté, chez les femmes minces, une glycémie élevée était liée à une adiposité néonatale augmentée. Ces associations sont indépendantes de la parité, du statut tabagique, du gain de poids durant la grossesse, des triglycérides maternels, du mode d’accouchement, du sexe du nouveau-né et de l’âge gestationnel à la naissance. Ces résultats suggèrent une régulation différentielle entre ces deux marqueurs métaboliques maternels et l’adiposité néonatale, selon le statut pondéral pré-grossesse. / Abstract: Worldwide, overweight and obesity in the pediatric population is a growing concern. Almost 21% of Canadian children aged 2 to 5 years are overweight and unfortunately, 6% of them are obese. Among those children, 80% will remain obese in adulthood leading to several health impacts. To prevent childhood obesity, we need to identify risk factors especially those occurring early in life. A particular importance was given to the fetal environment in establishing long-term metabolic health. Therefore, birth weight was often used as a marker of prenatal exposure. However, birth weight is a fairl y crude marker, and neonatal adiposity was previously identified as a stronger predictor of childhood adiposity. Two of the most important maternal determinants of fetal growth are maternal weight status and glycaemia during pregnancy. Recently, an adipoki ne have been suggested as a potential contributor to prenatal programming of obesity. Leptin is produced by adipocytes and plays an important role in energy balance and maybe on programming of postnatal obesity. During pregnancy, the placenta produces large amounts of leptin and 80% is secreted to the maternal side. Support ed by the fact that circulating maternal leptin levels reflects the placenta leptin production, our hypothesis was that maternal leptin levels are associated with neonatal adiposity, inde pendently of maternal glycaemia. We investigated levels of leptin over the course of an oral glucose tolerance test (OGTT) in pregnant women at 2nd trimester. We showed that higher maternal leptinemia is associated with greater adiposity in newborns of mot hers who were overweight/obese when entering pregnancy. While in lean women, higher glycaemia is associated with greater adiposity in newborns. These associations are independent of parity, maternal smoking status, maternal gestational weight gain, maternal triglyceride levels, delivery mode, neonate sex and gestational age at delivery. Those results suggest a differential regulation two important maternal metabolic marker and neonatal adiposity, according to maternal weight status.

<p><font face="TimesNewRomanPSMT"> <p align="left">Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure.</p> </font></p>

<p>Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure. In this study pregnant rats have been divided into 4 groups: a group which received nicotine (1mg/kg body weight/day) subcutaneously, a group that received the tomato juice only (6mg/kg body weight/day per os), a third group that received the combination of tomato juice ( 6mg /kg body weight/ day per os) and nicotine (1mg/kg body weight /day subcutaneously ) . The control group that received saline (1mg/kg body weight /day) subcutaneously and water. The injections were done during pregnancy and lactation until weaning at postnatal day 21. The results showed that maternal nicotine exposure during gestation and lactation leads to a gradual damage of the lung parenchyma and slower formation of the alveoli during the equilibrated phase of the lung growth leading to a decrease in the internal surface area required for gas exchange. Supplementation with tomato juice during gestation and lactation prevents all the adverse effects of maternal nicotine exposure on the lungs of the offspring. Since nicotine induce an increase in the oxidant levels of the mother and the fetus, my results imply that lycopene protected the lungs of the offsprings against the oxidants and thus against changes in the program that controls lung development as the animals age. This is supported by the observation that at postnatal day 84 the antioxidant.</p>

How to allocate resources in the health care sector is academically dealt with within the subject of health economics. Economic evaluations are within this area used to compare the costs and effects of medical interventions with the purpose to help decision makers decide how to allocate resources. Oxygen deficiency in the foetus during birth can lead to severe life long injuries in the child. In high-risk deliveries, it is therefore considered necessary to use foetal surveillance with a scalp electrode and the choice is between surveillance with internal cardiotocography (CTG) and surveillance with ST analysis. The standard procedure is in most hospitals currently CTG, which records the foetal heart rate and the uterine contractions. The second strategy, in this thesis referred to as ST analysis, complements CTG with foetal electrocardiography(ECG) and ST analysis. The objective of this report is to from a societal perspective determine the cost-effectiveness of using ST analysis in complicated deliveries, compared to the use of CTG alone. A cost-utility analysis was performed based on a probabilistic decision model incorporating the relevant strategies and outcomes. The costs and effects of the two different treatment strategies were compared in a decision tree. Discounted costs and quality-adjusted life-years (QALYs) were measured and simulated over a life-time perspective. The analysis resulted in an incremental effect of 0.005 QALYs for the ST analysis strategy, when compared to the CTG strategy. ST analysis was also associated with a €30 lower cost. Thus, CTG is dominated by the ST analysis strategy. The probability that ST analysis is the cost-effective alternative is high for all values of willingness-to-pay for a QALY, which means that a decision to implement the ST analysis strategy based on the results of this thesis would be surrounded by a low degree of uncertainty.

<p>How to allocate resources in the health care sector is academically dealt with within the subject of health economics. Economic evaluations are within this area used to compare the costs and effects of medical interventions with the purpose to help decision makers decide how to allocate resources.</p><p>Oxygen deficiency in the foetus during birth can lead to severe life long injuries in the child. In high-risk deliveries, it is therefore considered necessary to use foetal surveillance with a scalp electrode and the choice is between surveillance with internal cardiotocography (CTG) and surveillance with ST analysis. The standard procedure is in most hospitals currently CTG, which records the foetal heart rate and the uterine contractions. The second strategy, in this thesis referred to as ST analysis, complements CTG with foetal electrocardiography(ECG) and ST analysis.</p><p>The objective of this report is to from a societal perspective determine the cost-effectiveness of using ST analysis in complicated deliveries, compared to the use of CTG alone. A cost-utility analysis was performed based on a probabilistic decision model incorporating the relevant strategies and outcomes. The costs and effects of the two different treatment strategies were compared in a decision tree. Discounted costs and quality-adjusted life-years (QALYs) were measured and simulated over a life-time perspective.</p><p>The analysis resulted in an incremental effect of 0.005 QALYs for the ST analysis strategy, when compared to the CTG strategy. ST analysis was also associated with a €30 lower cost. Thus, CTG is dominated by the ST analysis strategy. The probability that ST analysis is the cost-effective alternative is high for all values of willingness-to-pay for a QALY, which means that a decision to implement the ST analysis strategy based on the results of this thesis would be surrounded by a low degree of uncertainty.</p>

<p><font face="TimesNewRomanPSMT"> <p align="left">Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure.</p> </font></p>