Genetic, prenatal and postnatal determinants of weight gain and obesity in young children – The STEPS Study

Genetic, Prenatal and Postnatal Determinants of Weight Gain and Obesity in Young Children – The STEPS Study University of Turku, Faculty of Medicine, Department of Paediatrics, University of Turku Doctoral Program of Clinical Investigation (CLIPD), Turku Institute for Child and Youth Research. Conditions of being overweight and obese in childhood are common health problems with longlasting effects into adulthood. Currently 22% of Finnish boys and 12% of Finnish girls are overweight and 4% of Finnish boys and 2% of Finnish girls are obese. The foundation for later health is formed early, even before birth, and the importance of prenatal growth on later health outcomes is widely acknowledged. When the mother is overweight, had high gestational weight gain and disturbances in glucose metabolism during pregnancy, an increased risk of obesity in children is present. On the other hand, breastfeeding and later introduction of complementary foods are associated with a decreased obesity risk. In addition to these, many genetic and environmental factors have an effect on obesity risk, but the clustering of these factors is not extensively studied. The main objective of this thesis was to provide comprehensive information on prenatal and early postnatal factors associated with weight gain and obesity in infancy up to two years of age. The study was part of the STEPS Study (Steps to Healthy Development), which is a follow-up study consisting of 1797 families. This thesis focused on children up to 24 months of age. Altogether 26% of boys and 17% of girls were overweight and 5% of boys and 4% of girls were obese at 24 months of age according to New Finnish Growth references for Children BMI-for-age criteria. Compared to children who remained normal weight, the children who became overweight or obese showed different growth trajectories already at 13 months of age. The mother being overweight had an impact on children’s birth weight and early growth from birth to 24 months of age. The mean duration of breastfeeding was almost 2 months shorter in overweight women in comparison to normal weight women. A longer duration of breastfeeding was protective against excessive weight gain, high BMI, high body weight and high weight-for-length SDS during the first 24 months of life. Breast milk fatty acid composition differed between overweight and normal weight mothers, and overweight women had more saturated fatty acids and less n-3 fatty acids in breast milk. Overweight women also introduced complementary foods to their infants earlier than normal weight mothers. Genetic risk score calculated from 83 obesogenic- and adiposity-related single nucleotide polymorphisms (SNPs) showed that infants with a high genetic risk for being overweight and obese were heavier at 13 months and 24 months of age than infants with a low genetic risk, thus possibly predisposing to later obesity in obesogenic environment. Obesity Risk Score showed that children with highest number of risk factors had almost 6-fold risk of being overweight and obese at 24 months compared to children with lowest number of risk factors. The accuracy of the Obesity Risk Score in predicting overweight and obesity at 24 months was 82%. This study showed that many of the obesogenic risk factors tend to cluster within children and families and that children who later became overweight or obese show different growth trajectories already at a young age. These results highlight the importance of early detection of children with higher obesity risk as well as the importance of prevention measures focused on parents. Keywords: Breastfeeding, Child, Complementary Feeding, Genes, Glucose metabolism, Growth, Infant Nutrition Physiology, Nutrition, Obesity, Overweight, Programming

Probiotic interventions in infancy: Benefit and Safety Assessment of Extended Applications

Immaturity of the gut barrier system in the newborn has been seen to underlie a number of chronic diseases originating in infancy and manifesting later in life. The gut microbiota and breast milk provide the most important maturing signals for the gut-related immune system and reinforcement of the gut mucosal barrier function. Recently, the composition of the gut microbiota has been proposed to be instrumental in control of host body weight and metabolism as well as the inflammatory state characterizing overweight and obesity. On this basis, inflammatory Western lifestyle diseases, including overweight development, may represent a potential target for probiotic interventions beyond the well documented clinical applications. The purpose of the present undertaking was to study the efficacy and safety of perinatal probiotic intervention. The material comprised two ongoing, prospective, double-blind NAMI (Nutrition, Allergy, Mucosal immunology and Intestinal microbiota) probiotic interventions. In the mother-infant nutrition and probiotic study altogether 256 women were randomized at their first trimester of pregnancy into a dietary intervention and a control group. The intervention group received intensive dietary counselling provided by a nutritionist, and were further randomized at baseline, double-blind, to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) or placebo. The intervention period extended from the first trimester of pregnancy to the end of exclusive breastfeeding. In the allergy prevention study altogether 159 women were randomized, double-blind, to receive probiotics (Lactobacillus rhamnosus GG) or placebo 4 weeks before expected delivery, the intervention extending for 6 months postnatally. Additionally, patient data on all premature infants with very low birth weight (VLBW) treated in the Department of Paediatrics, Turku University Hospital, during the years 1997 - 2008 were utilized. The perinatal probiotic intervention reduced the risk of gestational diabetes mellitus (GDM) in the mothers and perinatal dietary counselling reduced that of fetal overgrowth in GDM-affected pregnancies. Early gut microbiota modulation with probiotics modified the growth pattern of the child by restraining excessive weight gain during the first years of life. The colostrum adiponectin concentration was demonstrated to be dependent on maternal diet and nutritional status during pregnancy. It was also higher in the colostrum received by normal-weight compared to overweight children at the age of 10 years. The early perinatal probiotic intervention and the postnatal probiotic intervention in VLBW infants were shown to be safe. To conclude, the findings in this study provided clinical evidence supporting the involvement of the initial microbial and nutritional environment in metabolic programming of the child. The manipulation of early gut microbial communities with probiotics might offer an applicable strategy to impact individual energy homeostasis and thus to prevent excessive body-weight gain. The results add weight to the hypothesis that interventions aiming to prevent obesity and its metabolic consequences later in life should be initiated as early as during the perinatal period.

Muuttuvat tilat lasten- ja nuortenkirjallisuuden tutkijoiden pohdittavana : : metamorphic spaces in children's literature and culture 17.-19.1.2008 Jyväskylä

Ajankohtaista

Influenza in children – Diagnosis, treatment and prevention

Background: The burden of influenza on children is substantial. Although mortality rates are low, the incidence of influenza is highest in children, among whom also complications are frequent. A more accurate recognition of influenza in children could enable the rational use of antiviral drugs and help to avoid unnecessary courses of antibiotics. Limited data exists on the efficacy of oseltamivir treatment and the trivalent inactivated influenza vaccine (TIV) in children. Aims and methods: We sought for signs and symptoms that could help clinicians to diagnose influenza on clinical grounds in a case-control study in children <13 years of age. We further assessed the feasibility of different diagnostics methods during the early stage of the illness in children aged 1-3 years. The efficacy of early oseltamivir treatment (started <24h from the onset of symptoms) was evaluated in a randomized controlled trial (RCT) conducted in children 1-3 years of age, and the effectiveness of TIV to prevent laboratory-confirmed influenza was determined in a prospective, observational cohort study conducted among children aged 9 months to 3 years of age. Results: Fever was the only symptom predicting influenza in children. The sensitivity of conventionally used laboratory methods to detect influenza during the first 24h of illness was 92%. The sensitivity of the influenza rapid test in the same setting was 90% for influenza A and 25% for influenza B. Early oseltamivir treatment shortened the duration of the illness in children with influenza A by 3.5-4.0 days, but no efficacy was observed against influenza B. The effectiveness of TIV was 84% against the wellmatched influenza A, while no effectiveness against the mismatched influenza B was observed. Conclusions: Laboratory diagnostics are needed for a reliable diagnosis of influenza in children and were found sensitive already during the early stage of the illness. Early oseltamivir treatment was highly effective against influenza A, but no efficacy was seen against influenza B. TIV is effective also in young children if a good match between the vaccine and circulating strain is achieved.

Effects of physical activity and fitness on the psychological wellbeing of young men and working adults: associations with stress, mental resources, overweight and workability

Background: A positive association has been suggested to exist between physical activity and psychological wellbeing. However, the association between physical fitness, especially muscle fitness and psychological wellbeing, has not yet been fully elucidated. Aims: The objective of the present thesis was to assess the relationship between physical activity and physical fitness with stress symptoms, mental resources and workability among young men and working adults. Subjects and methods: Volunteers of young men (n=831, mean age 25-y (±4.0)), underwent a cardiorespiratory (CRF) and muscle fitness (MFI) test and completed leisure time physical activity (LTPA) and Occupational Stress Questionnaires (OSQ). The participants were divided into tertiles according to LTPA, CRF and MFI. A 12-month exercise intervention evaluated 371 working adults (exercise group, n=338, mean age 45-y (±8.8)); control group, n=33, mean age 41-y (±6.9)).The exercise group underwent a 12-month exercise program followed by a 12-month follow-up. The OSQ, Workability Index (WAI) and CRF were evaluated at baseline and at 4, 8, 12 and 24 months. Results: Physically inactive subjects reported more stress and less available mental resources than the subjects who reported high physical activity levels. Improved physical fitness was associated with less stress and more mental resources among normal weight men, but not in overweight men. After a 12-month exercise intervention, employees in the exercise group increased their physical activity, improved workability, decreased stress symptoms and improved their physical fitness and mental resources. After the follow-up year, workability and stress were improved compared to baseline. Conclusions: In this thesis, good physical fitness was associated with improved psychological wellbeing among young men and working adults.

Optimization and Measuring Techniques for Collect-and-Place Machines in Printed Circuit Board Industry

This thesis considers optimization problems arising in printed circuit board assembly. Especially, the case in which the electronic components of a single circuit board are placed using a single placement machine is studied. Although there is a large number of different placement machines, the use of collect-and-place -type gantry machines is discussed because of their flexibility and increasing popularity in the industry. Instead of solving the entire control optimization problem of a collect-andplace machine with a single application, the problem is divided into multiple subproblems because of its hard combinatorial nature. This dividing technique is called hierarchical decomposition. All the subproblems of the one PCB - one machine -context are described, classified and reviewed. The derived subproblems are then either solved with exact methods or new heuristic algorithms are developed and applied. The exact methods include, for example, a greedy algorithm and a solution based on dynamic programming. Some of the proposed heuristics contain constructive parts while others utilize local search or are based on frequency calculations. For the heuristics, it is made sure with comprehensive experimental tests that they are applicable and feasible. A number of quality functions will be proposed for evaluation and applied to the subproblems. In the experimental tests, artificially generated data from Markov-models and data from real-world PCB production are used. The thesis consists of an introduction and of five publications where the developed and used solution methods are described in their full detail. For all the problems stated in this thesis, the methods proposed are efficient enough to be used in the PCB assembly production in practice and are readily applicable in the PCB manufacturing industry.