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  • Zhang, Lei (Helsingin yliopisto, 2010)
    Dyslipidaemia, a major risk factor of cardiovascular disease (CVD), is prevalent not only in diabetic patients but also in individuals with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). The aims of this study were: 1) to investigate lipid levels in relation to glucose in European (Study I) and Asian (Study II) populations without a prior history of diabetes; 2) to study the ethnic difference in lipid profiles controlling for glucose levels (Study III); 3) to estimate the relative risk for cardiovascular mortality (Study IV) and morbidity (Study V) associated with dyslipidaemia in individuals with different glucose tolerance status. Data of 15 European cohorts with 19 476 subjects (I and III) and 13 Asian cohorts with 19 763 individuals (II and III) from 21 countries aged 25-89 years, without a prior history of diabetes at enrollment, representing Asian Indian, Chinese, European, Japanese and Mauritian Indian, were compared. The lipid-CVD relationship was studied in 14 European cohorts of 17 763 men and women which provided with follow-up data on vital status, with 871 CVD deaths occurred during the average 10-year follow-up (IV). The impact of dyslipidaemia on incidence of coronary heart disease (CHD) in persons with different glucose categories (V) was further evaluated in 6 European studies, with 9087 individuals free of CHD at baseline and 457 developed CHD during follow-up. Z-scores of each lipid component were used in the data analysis (I, II, IV and V) to reduce the differences in methodology between studies. Analyses of cardiovascular mortality and morbidity were performed using Cox proportional hazards regression analysis adjusting for potential confounding factors. Within each glucose category, fasting plasma glucose (FPG) levels were correlated with increasing levels of triglycerides (TG), total cholesterol (TC), TC to high-density lipoprotein (HDL) ratio and non-HDL cholesterol (non-HDL-C) (p<0.05 in most of the ethnic groups) and inversely associated with HDL-C (p<0.05 in some, but not all, of the populations). The association of lipids with 2-h plasma glucose (2hPG) followed a similar pattern as that for the FPG, except the stronger association of HDL-C with 2hPG. Compared with Central & Northern (C & N) Europeans, multivariable adjusted odd ratios (95% CIs) for having low HDL-C were 4.74 (4.19-5.37), 5.05 (3.88-6.56), 3.07 (2.15-4.40) and 2.37 (1.67-3.35) in Asian Indian men but 0.12 (0.09-0.16), 0.07 (0.04-0.13), 0.11 (0.07-0.20) and 0.16 (0.08-0.32) in Chinese men who had normoglycaemia, prediabetes, undiagnosed and diagnosed diabetes, respectively. Similar results were obtained for women. The prevalence of low HDL-C remained higher in Asian Indians than in others even in individuals with LDL-C < 3 mmol/l. Dyslipidaemia was associated with increased CVD mortality or CHD incidence in individuals with isolated fasting hyperglycaemia or IFG, but not in those with isolated post-load hyperglycaemia or IGT. In conclusion, hyperglycaemia is associated with adverse lipid profiles in Europeans and Asians without a prior history of diabetes. There are distinct patterns of lipid profiles associated with ethnicity regardless of the glucose levels, suggesting that ethnic-specific strategies and guidelines on risk assessment and prevention of CVD are required. Dyslipidaemia predicts CVD in either diabetic or non-diabetic individuals defined based on the fasting glucose criteria, but not on the 2-hour criteria. The findings may imply considering different management strategies in people with fasting or post-load hyperglycaemia.
  • Rosengård-Bärlund, Milla (Helsingin yliopisto, 2014)
    Diabetic autonomic neuropathy is a serious complication, associated with increased risk of morbidity and mortality, but it is perhaps the least understood of the diabetic complications. The challenge lies in the early diagnosis of this often subclinical condition, in the time window when it would still be treatable. Notably, when detected with the current diagnostic tools, diabetic autonomic neuropathy has been considered as the result of irreversible nerve damage. Reduced baroreflex sensitivity (BRS) is a sensitive marker of autonomic dysfunction, and importantly, also a prognostic marker in cardiovascular medicine. In addition to diabetes, abnormalities in the BRS also occur in conditions characterized by functional autonomic abnormalities such as myocardial infarction, heart failure, and hypertension. Accordingly, we hypothesized that early autonomic dysfunction in type 1 diabetes, as demonstrated by reduced BRS, is functional. The aim of this thesis was to elucidate the early markers of autonomic dysfunction in patients with type 1 diabetes of various durations. We reasoned that if BRS in patients with type 1 diabetes responds to slow, deep breathing, a manoeuvre shown to reduce sympathetic activity, or responds to oxygen administration, such a finding would support a functional aetiology. We also studied whether autonomic dysfunction, as established by reduced BRS, progresses alongside increasing diabetes duration to a stage where it is no longer improved by a functional manoeuvre. Moreover, we aimed to elucidate the role of BRS as a predictor of increased blood pressure (BP) level during a 5-year follow-up. We studied 117 patients with short (8.9±0.1 yrs) and 37 patients with long duration (33.7±0.5 yrs) type 1 diabetes, and a total of 73 age- and gender-matched, healthy control participants. Twelve heart-transplanted patients served as a model of cardiac denervation. An autonomic score was calculated from autonomic function tests. Spectral analysis of heart rate variability (HRV), blood pressure variability (BPV), and BRS came from recordings during normal (15/min) and slow, deep (6/min) controlled breathing. Of those with short-duration type 1 diabetes, 96 subjects were studied during a prospective visit by similar autonomic assessment as at baseline but in addition, with BRS assessed during inhalation of oxygen. In a total of 80 patients, we compared autonomic indices and ambulatory BP at baseline and follow-up. BRS was already reduced in patients with short-duration type 1 diabetes, but even more reduced in those with long duration or with increasing autonomic involvement. Slow breathing elevated the BRS to the level of control subjects at a normal breathing rate (15/min) in all patients except in those with an abnormal autonomic score. BRS also increased with oxygen during spontaneous breathing in diabetic but not in control participants, and with oxygen the difference in BRS was no longer significant. Slow breathing in normoxia restored the BRS to a similar extent as did oxygen. In the follow-up study, spontaneous BRS declined over time, but the change was not significant when adjusted for time of follow-up. Low BRS at baseline did not advance to cardiovascular autonomic neuropathy (CAN) but predicted an increase in night-time systolic BP. Furthermore, the BRS response to deep breathing at baseline predicted the increase found in 24-hour ambulatory BP. The results of this thesis indicate that even after long-duration diabetes, any abnormal BRS is at least in part of functional origin. The increased baroreflex response to oxygen supports the hypothesis of a functional reduction in parasympathetic activity occurring in patients with type 1 diabetes. The follow-up study showed that the decline in spontaneous BRS over time in patients with type 1 diabetes seems to be mainly due to normal ageing. Although early autonomic dysfunction seems functional and does not necessarily develop into autonomic neuropathy during a 5-year follow-up, the BRS and the response to deep breathing at baseline are associated with a future increase in BP. More research and a longer follow-up time will be required to fully clarify the prognostic significance of BRS in type 1 diabetes.
  • Mohebbi, Simin Z. (Helsingfors universitet, 2008)
    The present study assessed the prevalence of and risk factors for Early Childhood Caries (ECC) in children 12- to 36- month-old and evaluated the impacts of an educational intervention on ECC prevention in the 12- to 15-month-old cohort. The target population included 12- to 36-month-olds (n = 504) and their mothers attending the vaccination offices of 18 randomly selected public health centers of Tehran city. The mother was first interviewed by a structured questionnaire covering background factors, feeding habits, daytime sugar intake, mother’s and child’s oral cleaning habits, and mother’s perception toward her ability to maintain the child’s oral hygiene; then the child’s clinical dental examination was carried out covering caries experience and dental plaque status. In addition, the 12- to 15-month-olds (n = 242) were assigned to a six-month interventional study. The 18 health centers were randomly allocated into two groups for intervention and one for control. The mothers in the intervention groups received education on caries prevention from the vaccination staff with extra motivation as reminder phone calls in one of the intervention groups. The outcome was measured as differences in increments of enamel and dentinal caries. The results showed that the prevalence of ECC was rather high (3%-26%) in the three age groups, and almost all dmft was due to untreated caries. The majority of the children showed visible plaque on central upper incisors. Oral cleaning on a daily basis was reported for just 68% of mothers and 39% of children. The frequency of oral cleaning and good oral hygiene of the child were directly proportional to the mother’s own toothbrushing frequency. Of the children, 98% were solely or partly breastfed. ECC was more likely to occur among those for whom the burden of milk-bottle feeding at night existed (OR = 4.9), while breastfeeding per se, its duration, and its nighttime burden were not related to ECC. The indicator of daytime sugar intake also did not show a clear relationship with ECC. The educational intervention applying a pamphlet with some extra motivation and implemented by non-dental staff of public health centers appeared to be successful in preventing caries increments. To improve oral health status among the young children in countries with a developing oral health system, community-based oral health educational programs should be established by involving non-dental staff of health settings who are more frequently in contact with these children. Parents should be encouraged to realize that they play the dominant role in the oral health care of their children. Parents’ own oral health behaviors should be emphasized in dental and general health settings.
  • Toljamo, Tuula (Helsingin yliopisto, 2012)
    Chronic obstructive pulmonary disease (COPD) is an under-diagnosed and life-threatening progressive disease. Early symptoms of COPD include excessive sputum production and chronic cough. The primary risk factor of this disease in the western world is smoking. COPD is confirmed by spirometry, which does not totally reveal reversible airway obstruction. This study, conducted mainly in the Northern Finland, aimed to assess 1) smoking habits and smoking cessation in healthy middle-aged and young adults, 2) the prevalence of COPD and role of spirometry and prolonged respiratory symptoms in the diagnosis of COPD of smoking middle-aged adults, 3) the association of symptoms of chronic bronchitis with smoking habits in young adult males, and 4) to seek and to identify new potential biomarkers related to early COPD using non-hypothesis driven non-biased proteomics. A two-year prospective study included two visits to evaluate symptoms in healthy cigarette smokers, to screen new COPD cases and to assess the success of smoking cessation using motivational counselling and pharmacological therapies. In addition, a quantitative cross-sectional questionnaire survey was conducted in 1163 male conscripts during their military service in Northern Finland. A lung tissue proteomic approach was used to identify new COPD biomarkers. Spirometry revealed COPD by GOLD criteria in 11,0% and by national criteria in 15.3 % of originally asymptomatic chronic smokers. Further, chronic cough or sputum production was detected in 62.0% of the participants. After two years, 23.3% of adults had succeeded in quitting smoking. In young adults, 46.5% were daily smokers. The prevalence of self-reported chronic cough and sputum production was high in daily smokers (40.7%). The majority (60.2%) of the daily young smokers had made quit attempts and 46.9% of them had used nicotine replacement therapy (NRT). Based on the lung tissue proteomics, surfactant protein A (SP-A) was one of the most highly elevated spots in the COPD lung. The plasma SP-A concentration was higher both in chronic smokers and in COPD as compared to the non-smokers, and declined significantly during 2-year follow-up in those who succeeded to quit smoking compared to those who continued to smoke. To conclude there is remarkable burden of chronic bronchitis and COPD in the groups of chronic smokers who considered themselves as healthy. Motivational counselling seems to be successful, since over 23% of the adult smokers succeeded in stopping smoking. SP-A is a potential new biomarker for COPD although it needs further evaluation.
  • Gao, Weiguo (Helsingin yliopisto, 2010)
    Objectives of this study were to determine secular trends of diabetes prevalence in China and develop simple risk assessment algorithms for screening individuals with high-risk for diabetes or with undiagnosed diabetes in Chinese and Indian adults. Two consecutive population based surveys in Chinese and a prospective study in Mauritian Indians were involved in this study. The Chinese surveys were conducted in randomly selected populations aged 20-74 years in 2001-2002 (n=14 592) and 35-74 years in 2006 (n=4416). A two-step screening strategy using fasting capillary plasma glucose (FCG) as first-line screening test followed by standard 2-hour 75g oral glucose tolerance tests (OGTTs) was applied to 12 436 individuals in 2001, while OGTTs were administrated to all participants together with FCG in 2006 and to 2156 subjects in 2002. In Mauritius, two consecutive population based surveys were conducted in Mauritian Indians aged 20-65 years in 1987 and 1992; 3094 Indians (1141 men), who were not diagnosed as diabetes at baseline, were reexamined with OGTTs in 1992 and/or 1998. Diabetes and pre-diabetes was defined following 2006 World Health Organization/ International Diabetes Federation Criteria. Age-standardized, as well as age- and sex-specific, prevalence of diabetes and pre-diabetes in adult Chinese was significantly increased from 12.2% and 15.4% in 2001 to 16.0% and 21.2% in 2006, respectively. A simple Chinese diabetes risk score was developed based on the data of Chinese survey 2001-2002 and validated in the population of survey 2006. The risk scores based on β coefficients derived from the final Logistic regression model ranged from 3 – 32. When the score was applied to the population of survey 2006, the area under operating characteristic curve (AUC) of the score for screening undiagnosed diabetes was 0.67 (95% CI, 0.65-0.70), which was lower than the AUC of FCG (0.76 [0.74-0.79]), but similar to that of HbA1c (0.68 [0.65-0.71]). At a cut-off point of 14, the sensitivity and specificity of the risk score in screening undiagnosed diabetes was 0.84 (0.81-0.88) and 0.40 (0.38-0.41). In Mauritian Indian, body mass index (BMI), waist girth, family history of diabetes (FH), and glucose was confirmed to be independent risk predictors for developing diabetes. Predicted probabilities for developing diabetes derived from a simple Cox regression model fitted with sex, FH, BMI and waist girth ranged from 0.05 to 0.64 in men and 0.03 to 0.49 in women. To predict the onset of diabetes, the AUC of the predicted probabilities was 0.62 (95% CI, 0.56-0.68) in men and 0.64(0.59-0.69) in women. At a cut-off point of 0.12, the sensitivity and specificity was 0.72(0.71-0.74) and 0.47(0.45-0.49) in men; and 0.77(0.75-0.78) and 0.50(0.48-0.52) in women, respectively. In conclusion, there was a rapid increase in prevalence of diabetes in Chinese adults from 2001 to 2006. The simple risk assessment algorithms based on age, obesity and family history of diabetes showed a moderate discrimination of diabetes from non-diabetes, which may be used as first line screening tool for diabetes and pre-diabetes, and for health promotion purpose in Chinese and Indians.
  • Hukkinen, Katja (Helsingin yliopisto, 2007)
    The greatest effect on reducing mortality in breast cancer comes from the detection and treatment of invasive cancer when it is as small as possible. Although mammography screening is known to be effective, observer errors are frequent and false-negative cancers can be found in retrospective studies of prior mammograms. In the year 2001, 67 women with 69 surgically proven cancers detected at screening in the Mammography Centre of Helsinki University Hospital had previous mammograms as well. These mammograms were analyzed by an experienced screening radiologist, who found that 36 lesions were already visible in previous screening rounds. CAD (Second Look v. 4.01) detected 23 of these missed lesions. Eight readers with different kinds of experience with mammography screening read the films of 200 women with and without CAD. These films included 35 of those missed lesions and 16 screen-detected cancers. CAD sensitivity was 70.6% and specificity 15.8%. Use of CAD lengthened the mean time spent for readings but did not significantly affect readers sensitivities or specificities. Therefore the use of applied version of CAD (Second Look v. 4.01) is questionable. Because none of those eight readers found exactly same cancers, two reading methods were compared: summarized independent reading (at least a single cancer-positive opinion within the group considered decisive) and conference consensus reading (the cancer-positive opinion of the reader majority was considered decisive). The greatest sensitivity of 74.5% was achieved when the independent readings of 4 best-performing readers were summarized. Overall the summarized independent readings were more sensitive than conference consensus readings (64.7% vs. 43.1%) while there was far less difference in mean specificities (92.4% vs. 97.7%). After detecting suspicious lesion, the radiologist has to decide what is the most accurate, fast, and cost-effective means of further work-up. The feasibility of FNAC and CNB in the diagnosis of breast lesions was compared in non-randomised, retrospective study of 580 (503 malignant) breast lesions of 572 patients. The absolute sensitivity for CNB was better than for FNAC, 96% (206/214) vs. 67% (194/289) (p < 0.0001). An additional needle biopsy or surgical biopsy was performed for 93 and 62 patients with FNAC, but for only 2 and 33 patients with CNB. The frequent need of supplement biopsies and unnecessary axillary operations due to false-positive findings made FNAC (294 ) more expensive than CNB (223 ), and because the advantage of quick analysis vanishes during the overall diagnostic and referral process, it is recommendable to use CNB as initial biopsy method.
  • Ylihärsilä, Hilkka (Helsingin yliopisto, 2008)
    Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Thesis studies aimed to characterize associations between early growth and some components of the metabolic syndrome cluster. Participants belong to two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. In the 65-75 year old men and women, the well-known inverse relationship between birth weight and systolic blood pressure (SBP) was confined to people who had established hypertension. Among them a 1-kg increase in birth weight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in SBP. This relationship was further confined to people with the prevailing Pro12Pro polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene. People with low birth weight were more likely to receive angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03), and, again, this relationship was confined to the carriers of the Pro12Pro (p=0.01 for interaction). These results suggest that the inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the renin-angiotensin system leading to raised BP levels. Habitual physical activity protected men and women who were small at birth, and thus at increased risk for the development of type 2 diabetes, against glucose intolerance more strongly. Among subjects with birth weight ≤3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Rapid gain in body mass index (BMI), i.e. crossing from an original BMI percentile to a higher one, before the age of 2 years increased adult lean mass index (LMI, lean mass/height squared) without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in LMI, resulted in a relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.
  • Sandboge, Samuel (Helsingin yliopisto, 2015)
    Background. A small birth size, an indicator of a suboptimal intrauterine environment, is a risk factor for several non-communicable diseases (NCDs), a risk that in many cases is modified by childhood growth patterns. Regional variation in NCD prevalence could partly have its origin in early development. Lifestyle factors further influence NCD prevalence. Aims. We aimed to explore the associations between early growth and adult resting metabolic rate (RMR), body composition, non-alcoholic fatty liver disease (NAFLD), and hypertension. We also studied the associations between fructose intake and NAFLD, and differences in birth size between Helsinki and the Åland Islands. Subjects and methods. The Helsinki Birth Cohort Study consists of 13345 individuals born in Helsinki in 1934‒44. Detailed records are available for all participants including information on maternal and birth characteristics and measurements of childhood body size. 2003 individuals participated in a clinical study in 2001‒04 and 1083 of these additionally participated in a follow-up study in 2006‒08. The Åland records include 1697 births for the years 1937‒44. Results. The association between birth weight and RMR was inverse among women and quadratic among men. A higher attained adult weight than expected, based on weight and height measurements before age 11 years and adult height, was associated with higher adult body fat content. The odds ratio (OR) for NAFLD was 18.5 (95% CI 10.1; 33.6) among those who belonged to the lowest BMI tertile at age 2 years and subsequently were obese as adults, compared to those who were still lean or normal weight as adults. NAFLD was most common among individuals with the lowest dietary fructose intake. Systolic blood pressure (SBP) and the presence of hypertension were inversely associated with linear (height) growth between ages 2 and 11 years. Relative weight gain after age 11 years was positively associated with SBP. Ålandic babies born 1937‒44 were 87 grams (95% CI 61; 111) heavier and 0.4 cm (95% CI 0.3; 0.5) longer than their Helsinki peers. Conclusions. A more pronounced increase in relative weight after age 11 years than would be expected from previous body size, was positively associated with body fat content, NAFLD, and hypertension. Conversely, several growth measurements before age 11 years were negatively associated with the outcomes studied. None of the studied individuals were obese in childhood. Instead, a larger relative childhood body size in this group most likely represents a more beneficial childhood environment. Contrary to previous findings, we found that individuals with the highest fructose intake were least likely to suffer from NAFLD. We found a small but significant difference in birth size between the Åland Islands and Helsinki for the years 1937‒44.
  • Salonen, Minna (Helsingin yliopisto, 2011)
    The Developmental Origins of Health and Disease Hypothesis proposes that adverse health outcomes in adult life are in part programmed during fetal life and infancy. This means that e.g. restricted nutrition during pregnancy programmes the offspring to store fat more effectively, to develop faster and to reach puberty earlier. These adaptations are beneficial in terms of short term survival. However, in developed countries these adaptations often lead to an increased risk of obesity and metabolic disturbances in later life, due to a mismatch between the prenatal and postnatal environment. This thesis aimed to study the role of early growth in people who are obese as adults, but metabolically healthy as well as in those who are normal in weight but metabolically obese. Other study aims were to assess whether physical activity and cardiorespiratory fitness are programmed early in life. The role of socioeconomic status in the development of obesity from a life course setting was also studied. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their prenatal and childhood growth as well as living conditions. They participated in the detailed clinical examination during the years 2001-2004. A sub-group of the subjects participated in the UKK Institute 2-kilometre walk test. Metabolic syndrome was defined according to the 2005 criteria of the International Diabetes Federation. Among the obese men and women 20 % were metabolically healthy. Those with metabolic syndrome did not differ in birth size compared to the healthy ones, but by two years of age, they were lighter and thinner, and remained so up to 11 years. The period when changes in BMIs were predictive of the metabolic syndrome was from birth to 7 years. Of the normal weight individuals 17 % were metabolically obese. Again, there were no differences in birth size. However, by the age 7 years, those men who later developed metabolic syndrome were thinner. Gains in BMI during the first two years of life were protective of the syndrome. Children who were heavier, and especially taller, were more physically active, exercised with higher intensity and had higher cardiorespiratory fitness in their adult life than those who were shorter and thinner as children. Lower educational attainment and lower adult social class were associated with obesity in both men and women. Childhood social class was inversely associated with body mass index only in men while lower household income was associated with higher BMI in women. These results support the role of early life factors in the development of metabolic syndrome and adult life style. Early detection of risk factors predisposing to these conditions is highly relevant from a public health point of view.
  • Pesonen, Maria (Helsingin yliopisto, 2008)
    Atopy-related allergic diseases, i.e. allergic rhinoconjunctivitis, atopic dermatitis and asthma, have increased in frequency in the industrialized countries. In order to reverse this trend, effective preventive strategies need to be developed. This requires a better understanding of the early-life events leading to the expression of the atopic phenotype. The present study has aimed at defining early-life factors and markers associated with the subsequent development of allergic diseases in a cohort of 200 healthy, unselected Finnish newborns prospectively followed up from birth to age 20 years. Their mothers were encouraged to start and maintain exclusive breastfeeding as long as it was nutritionally sufficient for the infant. Consequently, all the infants received some duration of exclusive breastfeeding, 58% of the infants were on exclusive breastfeeding for the first 6 months of life, and 18% received this feeding at least for the first 9 months. Of the infants, 42% had a family history of allergy. After the first year of follow-up, the children were re-assessed at ages 5, 11 and 20 years with clinical examination, skin prick testing, and parental and personal interviews. Exclusive breastfeeding for over 9 months was associated with atopic dermatitis and symptoms of food hypersensitivity at age 5 years, and with symptoms of food hypersensitivity at age 11 years in the children with a familial allergy. Subjects with allergic symptoms or a positive skin prick test in childhood or adolescence had lower retinol concentrations during their infancy and childhood than others. An elevated cord serum immunoglobulin E concentration predicted subsequent atopic manifestations though with modest sensitivity. Children and adolescents with allergic symptoms, skin prick test positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the nonatopic subjects. In conclusion, prolonging strictly exclusive breastfeeding for over 9 months of age was not of help in prevention of allergic symptoms; instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood. Due to the modest sensitivity, cord serum IgE is not an effective screening method for atopic predisposition in the general population. Retinol and cholesterol concentrations in infancy were inversely associated with the subsequent development of allergic symptoms. Based on these findings, it is proposed that there may be differences in the inborn regulation of retinol and cholesterol levels in children with and without a genetic susceptibility to atopy, and these may play a role in the development of atopic sensitization and allergic diseases.
  • Alastalo, Hanna (Helsingin yliopisto, 2013)
    Experienced stress in childhood might have been so severe that it has effects throughout the life course. It has been suggested that early life stress may extend consequences on psychological and physical well-being. Previous findings focusing upon consequences of early life stress are however limited and mostly based upon retrospective studies. Still little is known about the consequences of early life stress, such as war separation on physical health from a longitudinal aspect. This thesis aimed to study cardiovascular mortality and morbidity in late adulthood among people who experienced separation without their parents to temporary foster care during World War II (WWII). Other study aims were to examine cardiovascular health, blood pressure levels and physical and psychosocial functioning in the separated participants. People who were not separated served as controls. Participants in this study belong to the Helsinki Birth Cohort Study (HBCS) which includes 13,345 people born in Helsinki between 1934 and 1944 and visited child welfare clinics in the city. Of these 13.5% had experienced evacuation abroad. Data on parental separation was obtained from National Archives, and information on use of medication or events on coronary heart disease (CHD), hypertension, stroke and cardiovascular deaths are obtained from national registers during a follow-up period from 1971-2002. Clinical study cohort included 2003 men and women who participated in the detailed clinical examination during the years 2001-2004. All these participants are included the cardiovascular health sub-study and of them 16.0% were separated participants. The blood pressure sub-study consist of 1361 non-obese subjects whose body mass index (BMI) were <30 kg/m2, of whom 14.1% had experienced evacuation abroad. The sub-study of physical and psychosocial functioning included 1803 people and of these separated participants were 14.8%. In all sub-studies the participants who did not experience war separation in childhood served as controls. Among the separated participants over one-third were separated in toddlerhood and approximately duration of separation was two years. The separated group were older and they have lower socioeconomic status in childhood and adulthood than among the non-separated controls. War separation was associated with higher CHD morbidity, the prevalence of cardiovascular disease (CVD) and diabetes. The separation in early childhood and the duration of separation were associated with higher CHD morbidity. Duration of separation over three years showed higher prevalence of CVD in later life. Despite this the evidence of higher hospitalizations and mortality was not found. In addition war separation predicted higher blood pressure levels in late adulthood and moreover increases in the risk of impaired physical functioning. The separation in early childhood was associated with higher blood pressure levels likewise duration in less than a year and over three years. The separation in school age and duration for over two years were associated with the later life lower physical functioning. The effects of separation in overall health were more pronounced among the separated men than women. These studies suggest that early life stress experience such as temporary parental separation may have consequences on cardiovascular health and general well-being through the lifespan. The war separation and its timing and duration are stressors, which could have long-term influence on critical development phases and thereby increases the risk of chronic non-communicable diseases in later life.
  • Sihvola, Elina (Helsingin yliopisto, 2010)
    Early-onset psychiatric illnesses effects scatter to academic achievements as well as functioning in familial and social environments. From a public health point of view, depressive disorders are the most significant mental health disorders that begin in adolescence. Using prospective and longitudinal design, this study aimed to increase the understanding of early-onset depressive disorders, related mental health disorders and developing substance use in a large population-derived sample of adolescent Finnish twins. The participants of this study, FinnTwin12, an ongoing longitudinal population-based study, came from Finnish families with twins born in 1983-87 (exhaustive of five birth cohorts, identified from Finland s Central Population Register). With follow-up ongoing at age 20-24, this thesis assessed adolescent mental health in the first three waves, starting from baseline age 11-12 to follow-ups at age 14 and 17½. Some 5600 twins participated in questionnaire assessments of a wide range of health related behaviors. Mental health was further assessed among an intensively studied subsample of 1852 adolescents, who completed also professionally administered interviews at age 14, which provided data for full DSM-IV/III-R (Diagnostic and Statistical Manual for Mental Health disorders, 4th and 3rd editions) diagnoses. The participation rates of the study were 87-92%. The results of the study suggest, that the diagnostic criteria for major depressive disorder (MDD) may not capture youth with clinically significant early-onset depressive conditions outside clinical settings. Milder cases of depression, namely adolescents fulfilling the diagnostic criteria for minor depressive disorder, a qualitatively similar condition to MDD with fewer symptoms are also associated with marked suicidal thoughts, plans and attempts, recurrences and a high degree of comorbidity. Prospectively and longitudinally, early-onset depressive disorders were of substantial importance in the context of other mental health disorders and substance use behaviors: These data from a large population-derived sample established a substantial overlap between early-onset depressive disorders and attention deficit hyperactivity disorder in adolescent females, both of them significantly predictive for development of substance use among girls. Only in females baseline DSM-IV ADHD symptoms were strong predictors of alcohol abuse and dependence and illicit drug use at age 14 and frequent alcohol use and illicit drug use at age 17.½ when conduct disorder and previous substance use were controlled for. Early-onset depressive disorders were also prospectively and longitudinally associated to daily smoking behavior, smokeless tobacco use, frequent alcohol use and illicit drug use and eating disorders. Analysis of discordant twins suggested that these predictive associations were independent of familial confounds, such as family income, structure and parental models. In sum, early-onset depressive disorders predict subsequent involvement of substance use and psychiatric morbidity. A heightened risk for substance use is substantial also among those depressed below categorical diagnosis of MDD. Whether early recognition and interventions among these young people hold potential for substance use prevention further in their lives has potential public health significance and calls for more research. Data from this population-derived sample with balanced representation of boys and girls, suggested that boys and girls with ADHD behaviors may differ from each other in their vulnerability to substance use and depressive disorders: the data suggest more adverse substance use outcome for girls that was not attenuated by conduct disorder or previous substance use. Further, the prospective associations of early-onset depressive disorders and future elevated levels of addictive substance use is not explained by familial factors supporting future substance use, which could have important implications for substance use prevention.
  • Bingham, Clarissa (Helsingin yliopisto, 2012)
    Men at the age of military service are in a transition phase between childhood home and independent adulthood. They are starting to make own decisions about their future and ways of life including also eating habits. In Finland, all men are liable to military service and a majority (nearly 80%) complete service. The increasing prevalence of overweight and obesity also among soldiers has raised concerns about conscripts eating habits. This doctoral dissertation studied eating habits of young men before and during military service, determinants of eating habits and associations between diet and health risk factors, and effects of an intervention promoting healthy eating in military conditions. Two datasets were used. In the first, data on conscripts food use and nutrient intake was collected in garrison, encampment and leave conditions. The second belonged to the VARU intervention study in which the supply of healthy food was increased in military eating environments i.e. garrison canteens and soldier s homes. Study questionnaires were collected before military service and during it at the 8th week and 6th month of service. Conscripts health status was also followed during service through 13 anthropometric and clinical risk factors. Main dietary outcomes were food indexes which were formed specifically for studying young men and to suit military conditions. Prior to military service, the diet was mainly healthy although fruit and vegetable consumption was clearly low. Upper secondary school and healthy behaviour predicted healthy eating. During military service, nutrient intake was adequate although salt intake was high and fibre intake low. Food at garrison met nutrition recommendations most and especially fibre-containing foods belonged to it. At fee-time, nutrient intake was less favourable and sugar consumption high. Nutrient-poor foods, such as soft drinks and pizza, were frequently used. Conscripts health risk factor levels were low. During service, overweight decreased and body composition improved. Blood pressure improved but lipid and glucose levels deteriorated. The intervention succeeded in improving conscripts eating habits. In intervention group, cereal foods were consumed more and several fat- and sugar-containing foods less than in control group. The intervention did not increase fruit and vegetable consumption. Positively, young men s everyday diet contained several healthy foods which consumption increased during military service. On the other hand, consumption of some unhealthy foods increased especially at free-time. Already in early adulthood, young men s eating habits, other health behaviours and health risk factors accumulate. Conscripts healthy eating habits can be supported by promoting the food supply in garrison canteens and soldier s homes. Effective intervening on individual choices, as low fruit and vegetable consumption, remains more challenging.
  • Leivo, Tiina (Helsingin yliopisto, 2001)
  • Sarkola, Taisto (Helsingin yliopisto, 2001)
  • Kausto, Johanna (Helsingin yliopisto, 2014)
    In Finland, partial sickness benefit is used to promote recovery and return to work (RTW) to full-time employment after sickness absence since 2007. This thesis aimed to examine the effectiveness and efficacy of the benefit and related partial sick leave on RTW, work retention and work participation mainly in four diagnostic categories: musculoskeletal diseases, mental disorders and traumas and tumors. The first of the five substudies was a literature review which investigated the empirical evidence on the use and effects of partial sick leave on RTW in the Nordic countries. Three of the substudies were longitudinal register-based studies examining the effects of partial sick leave on return to work, work retention and work participation in working populations with prolonged sickness absence. In addition, it was assessed whether the effects differed between men and women or by age, socioeconomic position or diagnostic category. The fifth study, a randomized controlled trial (RCT), focused on the efficacy of partial sick leave on sustained RTW at an earlier phase of work disability attributable to musculoskeletal diseases. Two register-based samples (n = 38 865 and n = 68 924) of the working population with prolonged sickness absence were drawn from the sickness insurance register of The Social Insurance Institution of Finland (SII). Comprehensive prospective and retrospective register data on work participation were collected from the national registers of the SII and the Finnish Centre for Pensions. There were methodological and analytical challenges in comparing work participation between the studied groups in the register-based substudies, namely the selection of individuals into partial sick leave and the complexity of the context. This was taken into account by investigating the study questions in different study samples, with different study designs and several statistical methods. A contrafactual approach with propensity score and difference-in differences methods were applied. A systematic search of literature was carried out in 2008 and replicated in 2012. A total of five methodologically rigorous studies from other Nordic countries were identified. In four of them, partial sick leave was associated with an increased likelihood of return to regular working hours or a higher subsequent employment rate. Some of the reviewed studies suffered from methodological limitations. The register-based substudies showed that both men and women on partial sick leave when compared with individuals on full sick leave, had their first recurrent sick leave sooner and they also had more periods of sick leaves during the follow up. Approximately 60% of subjects on partial sick leave and 30% of those on full sick leave had at least one recurrent sick leave during the follow up time. The adjusted risks of the first recurrent sick leave were 1.8 and 1.7 for men and women, respectively, when subjects on partial sick leave were compared with those on full sick leave. Partial sickness benefit reduced the risk (change in absolute risk) of full disability pension by 6% but conversely increased the risk of partial disability pension by 8% compared with full sick leave. In men, the use of full disability pension was reduced by 10% and in women by 4%. Corresponding 5% and 9% increases in the use of partial disability pension were detected. The effects were stronger in the group of mental disorders than in the group of musculoskeletal diseases. During a follow-up period of five years, the decline in work participation was 5% smaller among those on partial sick leave than in the comparison group. The favorable effect of partial sick leave on work participation was found in those aged from 45 to 65 years, in those with mental disorders and among those with a higher socioeconomic position. No major difference was found in the effect between men and women. In the RCT, both the intervention and the control group consisted of 31 participants with early work disability due to musculoskeletal diseases. In addition to the clinical data collected by the physicians, the participants filled in six questionnaires during the follow up year. Survey information was linked with register-based data on sickness absences and employment periods, obtained from the registers of the occupational health services and employers. Time to RTW sustained for at least four weeks was found to be shorter in the intervention group (median 12 versus 20 days, p = 0.10) and the fully adjusted hazard ratio of RTW was 1.8 (95% CI 1.2-2.8). Compliance with the intervention was high. Overall, the results were rather consistent across the four substudies revealing beneficial effects of partial sick leave on RTW and work participation irrespective of the methodological differences and varying outcomes. Partial sick leave was found to be an effective and efficient way of enhancing RTW and work participation. The findings of this study suggest that, even if the practice so far has been mainly benefitted by women, the use of partial sick leave can be recommended among men as well. Partial sick leave is a relevant measure both in musculoskeletal and mental disorders, at least in the context of the Finnish societal system. More attention needs to be paid to the implementation of the measure among young workers and individuals in physically strenuous, low pay jobs. To conclude, the overall results suggest that partial sickness benefit - if applied in a larger scale in the future - may prove to be an effective tool in increasing the work participation of working population with long term sickness absence.