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  • 201.
    Holmberg, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Induction of diabetes-related autoantibodies below cutoff for "positivity" in young nondiabetic children2003In: Annals of the New York Academy of Sciences, ISSN 0077-8923, Vol. 1005, p. 269-274Article in journal (Refereed)
    Abstract [en]

    The aim was to study the natural course of diabetes-related autoantibodies at low concentrations, below "positivity", in a nondiabetic population followed up from infancy. Blood samples were taken from 205 children at 6 weeks, 6 months, 18 months, and 5 years of age. Autoantibodies against GAD65 (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by radioligand-binding assays. All children had detectable levels of GADA and approximately half had IA-2A, but only approximately 10% had detectable levels of IAA during the follow-up period. Many children developed IA-2A already at 6 months of age, similar concentrations were seen at 18 months, and then the levels of IA-2A decreased until 5 years of age. GADA were induced less often at 6 months of age, increased up to 18 months, and fluctuated at similar levels up to 5 years of age. IAA were detectable in so few children and at low levels, so no trend in natural course could be revealed. We conclude that there is a natural induction of humoral immune response to β cell autoantigens early in life. Our results suggest that the mechanisms of β cell tolerance to GAD and IA-2 differ in healthy children.

  • 202.
    Holmberg, Hanna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Fälth-Magnusson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Induction of diabetes-related autoantibodies below cut-off for positivity in young non-diabetic children.2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, p. 317-Conference paper (Other academic)
  • 203.
    Host, A.
    et al.
    Høst, A., Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Halken, S.
    Department of Pediatrics, Odense University Hospital, Odense, Denmark.
    Muraro, A.
    Department of Pediatrics, University of Padua, Padua, Italy, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
    Dreborg, S.
    ESPACI, Lerum, Sweden.
    Niggemann, B.
    Department of Pneumology and Immunology, University Children's Hospital Charité, Humboldt University, Berlin, Germany.
    Aalberse, R.
    Department of Allergy CLB, Amsterdam, Netherlands.
    Arshad, S.H.
    Clinical Allergy Research Unit, St. Mary's Hospital, Newport, Isle of Wight, United Kingdom.
    Von, Berg A.
    Von Berg, A., Abt. für Kinderheilkunde, Marien-Hospital, Wesel, Germany.
    Carlsen, K.-H.
    Voksentoppen National Centre of Asthma, Allergy and Chronic, Lung Diseases in Children, Oslo, Norway.
    Duchen, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Eigenmann, P.A.
    Allergologie/Pediatrie, University of Geneve, Geneve, Switzerland.
    Hill, D.
    Department of Allergy, Royal Children's Hospital, North Melbourne, VIC, Australia.
    Jones, C.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Mellon, M.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Oldeus, G.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Oranje, A.
    Department of Dermatology and Venerology, ErasmusMC-University Medical Center, Sophia Children's Hospital Rotterdam, Rotterdam, Netherlands.
    Pascual, C.
    Servicio de Alergia, Hospital Infantil Universitario La Paz, Madrid, Spain.
    Prescott, S.
    Department of Paediatrics, University of Western Australia, Subiaco, WA, Australia.
    Sampson, H.
    Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Svartengren, M.
    Department of Public Health Sciences, Division of Occupational Medicine, Karolinska Hospital, Stockholm, Sweden.
    Wahn, U.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Warner, J.A.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Warner, J.O.
    Child Health, Southampton General Hospital, (803) Centre Block, Southampton, United Kingdom.
    Vandenplas, Y.
    A.Z.- Kinderen, Free University of Brussels, Brussels, Belgium.
    Wickman, M.
    Department of Environmental Health, Karolinska Hospital, Stockholm, Sweden.
    Zeiger, R.S.
    Kaiser Permanente San Diego, San Diego, CA, United States.
    Dietary prevention of allergic diseases in infants and small children: Amendment to previous published articles in Pediatric Allergy and Immunology 2004, by an expert group set up by the Section on Pediatrics, European Academy of Allergology and Clinical Immunology2008In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 19, no 1Article, review/survey (Refereed)
    Abstract [en]

    Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months. © 2008 The Authors.

  • 204.
    Hoven, Emma
    et al.
    Astrid Lindgren Childrens Hospital.
    Anclair, Malin
    Astrid Lindgren Childrens Hospital.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kogner, Per
    Astrid Lindgren Childrens Hospital.
    Boman, Krister K
    Astrid Lindgren Childrens Hospital.
    The Influence of Pediatric Cancer Diagnosis and Illness Complication Factors on Parental Distress2008In: Journal of pediatric hematology/oncology (Print), ISSN 1077-4114, E-ISSN 1536-3678, Vol. 30, no 11, p. 807-814Article in journal (Refereed)
    Abstract [en]

    Objective: We investigated how primary diagnosis and risk for diagnosis-related complication factors influence parental distress after a childs cancer diagnosis

    Methods: We used a model in which "complicated childhood cancers" were grouped into 1 category after identifying a set of potentially influential illness complication variables. This category included central nervous system tumors, acute myeloid leukemia, and bone tumors. Parental distress in that category (n = 144) was compared with distress after acute lymphoblastic leukemia (n = 177) in the child. In addition, comparisons were made between parents of the specific diagnosis groups. A multidimensional questionnaire assessing symptoms of distress was used.

    Results: Parents in the complicated cancer category showed significantly heightened disease-related fear, anxiety, depression, loss of control, late effects-related uncertainty, and poorer self-esteem compared with parents of children with acute lymphoblastic leukemia. Significantly heightened parental distress was associated with the child having been treated with cranial irradiation.

    Conclusions: Relatively heightened distress in parents of children with complicated cancer is influenced by diagnosis-related factors like an intricate prediagnostic phase, and uncertainty about late effects. Heightened vulnerability to distress signals exceptional needs for support and information among parents of children treated for central nervous system or bone tumors.

  • 205.
    Hultman, Elin
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Alm, Charlotte
    Stockholm University, Sweden .
    Cederborg, Ann-Christin
    Stockholm University, Sweden .
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Vulnerable children's health as described in investigations of reported children2013In: Child & Family Social Work, ISSN 1356-7500, E-ISSN 1365-2206, Vol. 18, no 2, p. 117-128Article in journal (Refereed)
    Abstract [en]

    This study explores whether the social services weigh in health aspects, and what these may be, when investigating reported childrens life situation. Information about physical and psychological health aspects for 259 children in 272 investigations was included. Overall, information about childrens health was limited. Problematic emotions were the most commonly reported health aspect in the investigations, whereas suicidal thoughts, self-harm behaviour and gastrointestinal and renal diseases were mentioned least of all. A cluster analysis revealed that the low level of health information group included the largest sample of data and consisted of investigations with minimal information about childrens health. The three other cluster groups, Neurological diseases and psychosomatic symptoms, Emotional health and Physical and psychological health and destructive behaviour, consisted of investigations conducted mostly according to the model called Childrens Needs In Focus (BBIC, in Swedish, Barns Behov i Centrum). Although these investigations also produced limited information, they provided more than those assessed as having a low level of information about health aspects. The conclusion is that it is necessary to increase information about health aspects in investigations if social welfare systems are to be able to fulfil their ambition of supporting vulnerable childrens need of health care.

  • 206.
    Hultman, Elin
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Cederborg, Ann-Christin
    Stockholm University, Sweden .
    Fälth-Magnusson, Karin
    Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Social workers’ assessments of children’s health when arguing for children’s needs2015In: Child and Adolescent Social Work Journal, ISSN 0738-0151, E-ISSN 1573-2797, Vol. 32, no 4, p. 301-308Article in journal (Refereed)
    Abstract [en]

    In Sweden, child-related social services constitute an institutional body that conducts both preventive and supportive work for children in need of health support. However, in the social services Act (2001:453) there are few concrete statements about how social workers should assess children’s health. In this study we therefore explore how social workers in Sweden adapt to the task of assessing children’s health. Specifically, we investigate the ways in which children’s health is explained in the context of reaching conclusions about the concrete needs of children. Inspired by a social constructionist and discursive analytical approach we analysed 60 written investigations where health concerns were expressed at the point of initiating an investigation. The findings are that social workers limited their assessments of children’s health, using only a few words when mentioning health aspects. There was a difference in how they described physical- and psychological health problems. When they did pay attention to children’s psychological health this was mostly carried out with the use of one single explanation for the cause of the health condition; parental misbehaviour. Besides, this explanation fitted the suggested support. Signs of children’s psychological problems were described by their own destructive behaviour. Physical health was only briefly mentioned and the recommendations for child support involved external assistance. This means that social workers could use a simplified explanatory model lacking descriptions of each child’s life situation. This way of limiting assessment may hinder a deeper understanding of causes and consequences and thereby impose limits on specifying the particular support the child needs.

  • 207.
    Huus, Karin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Ludvigsson, Jonas F.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Enskär, Karin
    Department of Nursing Science, School of Health Sciences, J ¨onk¨ oping, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Risk factors in childhood obesity—findings from the All Babies In SoutheastSweden (ABIS) cohort2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 9, p. 1315-1320Article in journal (Refereed)
    Abstract [en]

    Aim: Our objective was to investigate whether overweight at a very young age predicts overweight at 5 years and to identify risk factors for overweight/obesity at 5 years, thereby making it easier for Child Health Services to focus their prevention strategies on risk groups.

    Methods: We analysed data from the ABIS study (All Babies In Southeast Sweden), a prospective cohort study. Parents answered questionnaires between childbirth (n = 16,058) and 5 years (n = 7356).

    Results: High body mass index (BMI; >95th percentile) at 1 year (adjusted odds ratio [AOR]= 6.57; 95% CI = 4.63–9.33; p < 0.001) and age-adjusted BMI > 25 at 2.5 years (AOR = 14.24; 95% CI = 10.52–19.29; p < 0.001) were associated with increased risk of obesity (age-adjusted BMI > 30) at 5 years. Heredity for type 2 diabetes (p = 0.022), high parental BMI and the child's own BMI at birth and at 1 year predicted higher BMI of the child at 5 years (p < 0.001). High parental education was inversely associated with child overweight (p = 0.054 respective p < 0.005).

    Conclusion: Obesity at age 1 and at 2.5 years predicts obesity at 5 years. Obese parents, especially in families with heredity for type 2 diabetes and low education, should be targeted in early obesity prevention strategies by the Child Health Service.

  • 208.
    Huus, Karina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Brekke, Hilde K
    Department of Clinical Nutrition, Sahlgrenska Academy at G¨ oteborg University, Sweden.
    Ludvigsson, Jonas F
    Deptartment of Paediatrics, Örebro University Hospital, Sweden/Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Sweden.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Relationship of food frequencies as reported by parents to overweight and obesity at 5 years2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 1, p. 139-143Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate if food frequencies are related to overweight/obesity in 5-year-old children.

    Methods: During 1997-1999, 21 700 infants were invited to participate in ABIS (All Babies in Southeast Sweden), a prospective, cohort study. Participants were followed from birth (n = 16 058) to 5 years (n = 7356). Food frequencies reported by parents at 2.5 and 5 years were studied in the relation to overweight/obesity at 5 years using multiple logistic regressions. A p-value < 0.01 was considered statistically significant.

    Results: At 2.5 years frequencies of intake of cheese were positively associated with overweight/obesity at 5 years while porridge, fried potatoes/french fries and cream/creme fraiche showed a negative association. When adjusting for known risk factors, porridge and fried potatoes/french fries remained negatively associated with overweight/obesity. At 5 years, chocolate and lemonade were positively associated with overweight/obesity whereas cream/creme fraiche, pastries and candy were negatively associated. Candy remained negatively associated to overweight/obesity after adjustment for potential confounders.

    Conclusion: Food frequencies do not offer any simple explanation for overweight/obesity. Porridge at 2.5 years may protect against overweight/obesity at 5 years, while lemonade may contribute to overweight. Our finding that fried potatoes/french fries may protect against overweight/obesity is unexpected and must be interpreted with caution. These findings should be confirmed by prospective studies using objective recordings.

  • 209.
    Huus, Karina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Ludvigsson, Jonas F.
    Department of Pediatrics, Clinical Research Centre, Örebro University Hospital, Sweden and Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Sweden.
    Enskär, Karin
    Department of Nursing Science, School of Health Sciences, Jönköping, Sweden.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Exclusive breastfeeding of Swedish children and its possible influence on the development of obesity: a prospective cohort study2008In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 8, no 42Article in journal (Refereed)
    Abstract [en]

    Background: Overweight and obesity are increasing among children all over the world. Socio-economic factors may influence the development of overweight and obesity in childhood, and it has been proposed that breastfeeding may protect against obesity. The aim of our study was to examine the relationship between exclusive breastfeeding and obesity when potential confounders, such as socioeconomic factors, are considered.

    Methods: The data analyzed was from ABIS (All Babies in Southeast Sweden), a prospective cohort study. All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden (n = 21,700) were asked to participate. Parents were asked to answer periodic questionnaires from the time of the child's birth (n = 16,058) until he/she was five years of age (n = 7,356). Cutoffs for overweight and obesity were defined according to Cole et al, age and gender adjusted. Short-term exclusive breastfeeding was defined as < 4 months of exclusive breastfeeding. Multiple logistic regressions were used to identify variables that predict the child's BMI (Body Mass Index) at five years of age.

    Results: At five years of age, 12.9% of the children in the study wereoverweight and 4.3% were obese. At the age of three months, 78.4% of the children were being breastfed exclusively. The median exclusive breastfeeding duration was four months. High maternal BMI > 30 (AOR = 1.07; CI = 1.05–1.09; P < 0.001), maternal smoking (AOR = 1.43; CI = 1.05–1.95; P = 0.023) and being a single parent (AOR = 2.10; CI = 1.43–3.09; P < 0.001) were associated with short-term exclusive breastfeeding (less than 4 months). Short-term exclusive breastfeeding was less common if one of the parents had a university degree (Mother: AOR = 0.74; CI = 0.61–0.90; P = 0.003 Father: AOR = 0.73; CI = 0.58–0.92; P = 0.008) or if the father was more than 37 years old (AOR = 0.74; CI = 0.55–0.99; P = 0.045). Short-term exclusive breastfeeding was associated with obesity in five-year-old children (simple logistic regression: OR = 1.44; CI = 1.00–2.07; P = 0.050), but when including other independent factors in the analysis, short-term exclusive breastfeeding did not attain statistical significance.

    Conclusion: We cannot exclude the possibility that exclusive breastfeeding influences weight development, but it does not seem to protect against obesity at five years of age.

  • 210.
    Huus, Karina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Raustorp, Anders
    School of Human Sciences University of Kalmar, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Physical activity, blood glucose and c-peptide in healthy school-children2010Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of type 1 diabetes is increasing. This increase must be due to environmental factors. Low physical activity and overweight/obesity among children may play a role.

    Objective: The aim of the current study was to investigate how lack of physical activity relates to blood glucose value and insulin sensitivity in healthy children. A second aim was to explore whether low physical activity is related to overweight/obesity in children.

    Methods: This study is part of the prospective cohort study ‘All Babies In southeast Sweden’ (ABIS). 199 children from different schools participated. Pedometersteps during 4 days were registered as well as height and weight, and fasting blood glucose and serum C-peptide were determined. Parents answered a questionnaire.

    Results: Fewer dailysteps correlated to higher BMI (P= 0.019) and waist circumference (P=0.018) as well as to higher C-peptide (P= 0.044), HOMA IR (P=0.046) and HOMA β-cell (P=0.022). Children who spent more hours/day in front of TV/Video had higher waist circumference (P= 0.033) and higher fasting blood glucose values (P=0.016).

    Conclusion: Already in early school-age low physical activity is related to increased BMI and waist circumference. These signs and low physical activity are accompanied by a decreased insulin sensitivity compensated for by significantly increased insulin secretion. Low physical activity may cause beta cell stress which might contribute to an autoimmune process in individuals predisposed to autoimmunity, and thereby to the increasing incidence of Type 1 diabetes in children.

  • 211.
    Hyllienmark, Lars
    et al.
    Karolinska Institute, Sweden .
    Alstrand, Nils
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Jonsson, Bjorn
    Uppsala University, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Cooray, Gerald
    Karolinska Institute, Sweden .
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 10, p. 3187-3194Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P andlt; 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P andlt; 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P andlt; 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P andlt; 0.002) than with follow-up HbA(1c) ( = 0.034, P andlt; 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.

  • 212.
    Hyllienmark, Lars
    et al.
    Avd f Klin neurofysiologi Karolinska sjukhuset, Stockholm.
    Maltez, J
    Avd f Klin neurofysiologi Karolinska sjukhuset, Stockholm.
    Dandenell, AnnaKarin
    Barnkliniken US.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Brismar, Tom
    Avd f Klin Neurofysiologi Karolinska sjukhuset, Stockholm.
    EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes2005In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 48, no 3, p. 412-419Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: The aim of the present study was to identify whether adolescents with type 1 diabetes receiving modern multiple insulin injection therapy (MIT) have abnormal EEGs, and to elucidate possible correlations with a history of severe hypoglycaemia, poor metabolic control and nerve conduction defects. Methods: We investigated 35 patients (age 14-19 years) with disease duration 7.6±4.6 years, and 45 healthy control subjects. EEG spectral components were obtained from 15-min recordings in resting, awake subjects. Nerve conduction was measured bilaterally in motor and sensory fibres in the median, peroneal and sural nerves. Results: The EEGs of patients showed an increase in slow activity (delta and theta) and a reduction in alpha peak frequency, both of which were most pronounced in the frontal regions (p<0.001). They also showed a decrease in fast activity, which was most pronounced bilaterally in the posterior temporal regions (alpha p<0.001, beta p<0.01, gamma p<0.001). A history of severe hypoglycaemia was correlated with a global increase in theta activity (p<0.01-0.05). Poor metabolic control, measured as acute and long-term HbA1c levels, was correlated with an increase in delta activity and a decrease in alpha peak frequency. The decrease in fast activity in the temporal regions was a separate type of abnormality because it had a different distribution, and was not correlated with the increase in delta/theta power, poor metabolic control or with hypoglycaemia. Conclusions/interpretation: Recurrent severe hypoglycaemia and poor metabolic control are risk factors for EEG abnormalities in adolescents with type 1 diabetes receiving MIT treatment. In addition, we found pronounced abnormalities in the temporal regions that were not related to these risk factors. © Springer-Verlag 2005.

  • 213.
    Hällgren, Anita
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Burman, L
    Olsson-Liljequist, B
    Isaksson, Barbro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Saedi, B
    Walther, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hanberger, Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Hög frekvens an korskolonisering med resistenta enterokocker hos "långliggare" på IVA2004In: Hygiea,2004, 2004, p. 57-57Conference paper (Other academic)
  • 214.
    Högberg, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Webb, C
    Lund University.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Danielsson, L
    Norrtalje Hospital.
    Ivarsson, A
    Umea University.
    Sandstrom, O
    Umea University.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine2011In: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 100, no 7, p. 1023-1027Article in journal (Refereed)
    Abstract [en]

    Aim: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. Methods: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. Results: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p andlt; 0.001). Conclusion: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.

  • 215.
    Ivars, Katrin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nelson, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Mörelius, Evalotte
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nasopharyngeal suctioning does not produce a salivary cortisol reaction in preterm infants2012In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 101, no 12, p. 1206-1210Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate whether nasopharyngeal suctioning produces a physiological and behavioural stress reaction in preterm infants and if a possible reaction can be dampened by sweet solution. Methods: Eleven preterm infants were randomly assigned to receive either 30% oral glucose or nothing prior to morning nasopharyngeal suctioning; the procedure was reversed in the afternoon. The study included a total of 44 samples from preterm infants evaluated with salivary cortisol, pain score (Visual Analogue Scale), heart rate, oxygen saturation and recovery time through the Newborn Individualized Developmental Care and Assessment Program. For reference, 44 samples from eleven full-term infants were evaluated for salivary cortisol. Results: Regardless of whether or not preterm infants received glucose before nasopharyngeal suctioning, no statistically significant difference was found in salivary cortisol reactivity, pain score, heart rate, oxygen saturation or recovery time. Nor were any statistically significant differences between salivary cortisol baseline and response values found in full-term infants after nasopharyngeal suctioning. Conclusion: In the present setting, nasopharyngeal suctioning was not stressful enough to increase salivary cortisol or pain score. Oral glucose did not alter salivary cortisol levels.

  • 216.
    Jakobsson, Hedvig E
    et al.
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Harris, Keith
    School of Engineering, University of Glasgow, Glasgow, UK .
    Quince, Christopher
    School of Engineering, University of Glasgow, Glasgow, UK .
    Jernberg, Cecilia
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden .
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Anders F
    KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Gene Technology, Solna, Sweden.
    Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 4, p. 559-566Article in journal (Refereed)
    Abstract [en]

    Objective The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response.

    Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months.

    Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood.

    Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.

  • 217.
    Jamali, Reza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Mohseni, Simin
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Continuous monitoring of the subcutaneous glucose level in freely moving normal and diabetic rats and in humans with Type I diabetes2002In: Diabetes Technology and Therapeutics, ISSN 1520-9156, Vol. 4, no 3, p. 305-312Article in journal (Refereed)
    Abstract [en]

    Laboratory animals are extensively used in diabetic research. However, it is not known whether the glucose dynamics in laboratory animals are similar to the dynamics in humans. The aim of the present study is to see whether the Medtronic MiniMed continuous subcutaneous glucose monitoring system can be used to record fluctuations of the glucose level in freely moving normal and insulin-treated diabetic rats. The monitoring system was applied during 3 days to normal and diabetic hyperglycemic and hypoglycemic rats treated with insulin implants. Corresponding data from type 1 diabetic patients with poor glycemic control were selected retrospectively in order to note the similarities and differences. In normal rats the subcutaneous glucose level varied slightly (median = 111 mg/dL). In hyperglycemic rats the subcutaneous glucose values fluctuated markedly around a median of 226 mg/dL. The fluctuations formed a short-wave pattern with a low amplitude, superimposed on a long-wave pattern with a high amplitude. The subcutaneous glucose profile seen in type 1 diabetic patients (median = 180 mg/dL) was similar to that observed in hyperglycemic rats. In hypoglycemic rats, the subcutaneous glucose level fluctuated moderately around a median of 55 mg/dL. In these rats the fluctuations formed a short-wave pattern with low amplitude, without any obvious long-wave pattern. The subcutaneous glucose values conformed to corresponding blood glucose measurements. We conclude that the Medtronic MiniMed continuous glucose monitoring system can be used to record the subcutaneous glucose level over time in freely moving rats.

  • 218.
    Jenmalm, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Immune responses to birch during the first seven pollen seasons of life2001In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 124, no 1-3, p. 321-323Conference paper (Other academic)
    Abstract [en]

    Background: Exposure to allergens early in life may have an impact on the incidence of allergy many years later, but the kinetics of the immune responses have still not been studied prospectively. Therefore, we wanted to study the development of immune responses of the Th1 and Th2 type to birch over the first pollen seasons. Material and Methods: Blood samples were obtained from 21 prospectively followed children during the second to the seventh pollen season of life. IgG subclass antibodies to rBet v 1 were analyzed by ELISA, IgE antibodies to birch with Magic Lite™ and birch-induced mononuclear cell proliferation by 3H-thymidine incorporation. Results: Proliferative responses and IgG1 antibodies were commonly seen both in children with and without allergic symptoms and sensitization to birch. Most nonsensitized children had a transient IgG4 antibody response, which was downregulated after the third pollen season, while the titers of this Th2-associated subclass increased with age in sensitized children with clinical symptoms to birch. Conclusions: Immune responses to birch can be demonstrated in children regardless of atopic status. A transient early Th2-like response is downregulated after the third pollen season in nonatopic but not atopic children. Copyright © 2001 S. Karger AG, Basel.

  • 219.
    Jenmalm, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Duchén, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Timing of allergy-preventive and immunomodulatory dietary interventions: are prenatal, perinatal or postnatal strategies optimal?2013In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, no 3, p. 273-278Article, review/survey (Refereed)
    Abstract [en]

    The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid (LCPUFA) ratio, resulting in an abnormal postnatal immune maturation. The timing of allergy-preventive probiotic and ω-3 LCPUFA interventions is critical, as early-life events occurring during critical windows of immune vulnerability can have long-term impact on immune development. The maternal dietary and microbial environment during pregnancy may programme the immune development of the child. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment, but potentially also increasing disease susceptibility in the offspring if exposures are mismatched. Although the importance of fetal programming mostly has been studied in cardiovascular and metabolic disease, this hypothesis is also very attractive in the context of environmentally influenced immune-mediated diseases. This review focuses on how prenatal, perinatal or postnatal ω-3 LCPUFA interventions regulate childhood immune and allergy development, and if synergistic effects may be obtained by simultaneous probiotic supplementation. We propose that combined pre- and postnatal preventive measures may be most efficacious. Increasing knowledge on the immunomodulatory effects of prenatal, perinatal and postnatal interventions will help to direct future strategies to combat the allergy epidemic.

  • 220.
    Jenmalm, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Macaubas, C
    Fac Hlth Sci, Div Paediat, Linkoping, Sweden TVW Telethon Inst Child Hlth Res, Perth, WA, Australia.
    Holt, P
    Holt, B
    Smallacombe, T
    Fac Hlth Sci, Div Paediat, Linkoping, Sweden TVW Telethon Inst Child Hlth Res, Perth, WA, Australia.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Allergen induced cytokine responses at birth in relation to development of atopic disease and sensitisation2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, no 1, p. 329-Conference paper (Other academic)
  • 221.
    Jennersjö, Pär
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 9, p. 1119-1125Article in journal (Refereed)
    Abstract [en]

    Diabet. Med. 29, 11191125 (2012) Abstract Aims The aim of this study was to explore the association between pedometer-determined physical activity versus measures of obesity, inflammatory markers and arterial stiffness in people with Type 2 diabetes. Methods We analysed data from 224 men and 103 women with Type 2 diabetes, aged 5466 years. Physical activity was measured with waist-mounted pedometers during three consecutive days and the number of steps/day were calculated and classified in four groups: andlt; 5000 steps/day, 50007499 steps/day, 75009999 steps/day and andgt;= 10000 steps/day. Blood samples were analysed for lipids, HbA1c, inflammatory markers including C-reactive protein and interleukin-6. Nurses measured blood pressure and anthropometrics. Aortic pulse wave velocity was measured with applanation tonometry over the carotid and femoral arteries. Results Mean steps/day was 7683 +/- 3883 (median 7222, interquartile range 486910 343). There were no differences in age, diabetes duration, blood pressure, lipids or glycaemic control between the four groups of pedometer-determined physical activity. Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m2, P andlt; 0.001), waist circumference (101.7 vs. 108.0 cm, P andlt; 0.001), lower levels of C-reactive protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin-6 (1.9 vs. 3.8 pg ml, P andlt; 0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009) compared with less physically active people. Conclusions We conclude that physical activity measured with pedometer was associated not only with less abdominal obesity, but also with decreased systemic low-grade inflammation as well as with low arterial stiffness, in people with Type 2 diabetes.

  • 222.
    Jogi, R.
    et al.
    Jõgi, R., Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden, Foundation Tartu University Clinics Lung Clinic, Tartu, Estonia.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Boman, G.
    Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden, Asthma Research Centre, Uppsala University, Uppsala, Sweden.
    Jonson, Carl-Oscar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of atopy2002In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no 7, p. 525-529Article in journal (Refereed)
    Abstract [en]

    The study is a part of the European Community Respiratory Health Survey. A random sample (n=351) of 20-44-year olds and persons of the same age with asthma-like symptoms or current asthma medication according to a postal questionnaire (n=95) were studied. Interview was taken, methacholine challenge was done and ECP, total and specific IgE were measured from serum. The median S-ECP value was 8.0 µg/l in the random sample. The geometric mean of S-ECP was higher in subjects with, than without atopy (10.2. vs 8.9 µg/l, P < 0.01) and in subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR (9.9 vs 8.0 µg/l, P <0.01).The levels correlated weakly to forced expiratory volume in one second (FEV1) (r=0.13, P <0.01) and were not independently correlated with respiratory symptoms, asthma or FEV1 after adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the level of eosinophil activation is low in a population with a low prevalence of atopy even when BHR is common. © 2002 Published by Elsevier Science Ltd.

  • 223.
    Johansson, AnnaKarin
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    How should parents protect their children from environmental tobacco-smoke exposure in the home?2004In: Pediatrics, ISSN 1098-4275, Vol. 113, no 4, p. 291-295Article in journal (Refereed)
    Abstract [en]

    Background. Children’s exposure to tobacco smoke is known to have adverse health effects, and most parents try to protect their children.

    Objective. To examine the effectiveness of parents’ precautions for limiting their children’s tobacco-smoke exposure and to identify variables associated to parents’ smoking behavior.

    Design and participants. Children, 2.5 to 3 years old, participating in All Babies in Southeast Sweden, a prospective study on environmental factors affecting development of immune-mediated diseases. Smoking parents of 366 children answered a questionnaire on their smoking behavior. Cotinine analyses were made on urine specimen from these children and 433 age-matched controls from nonsmoking homes.

    Results. Smoking behavior had a significant impact on cotinine levels. Exclusively outdoor smoking with the door closed gave lower urine cotinine levels of children than when mixing smoking near the kitchen fan and near an open door or indoors but higher levels than controls.

    Variables of importance for smoking behavior were not living in a nuclear family (odds ratio: 2.1; 95% confidence interval: 1.1–4.1) and high cigarette consumption (odds ratio: 1.6; 95% confidence interval: 1.2-2.1).

    An exposure score with controls as the reference group (1.0) gave an exposure score for outdoor smoking with the door closed of 2.0, for standing near an open door + outdoors of 2.4, for standing near the kitchen fan + outdoors of 3.2, for mixing near an open door, kitchen fan, and outdoors of 10.3, and for indoor smoking of 15.2.

    Conclusion. Smoking outdoors with the door closed was not a total but the most effective way to protect children from environmental tobacco-smoke exposure. Other modes of action had a minor effect.

  • 224.
    Johansson, AnnaKarin
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Parents' attitudes to children's tobacco smoke exposure and how the issue is handled in health care2004In: Journal of Pediatric Health Care, ISSN 0891-5245, Vol. 18, no 5, p. 228-235Article in journal (Refereed)
    Abstract [en]

    Introduction

    The objective of the study was to understand the opinions and attitudes among parents of preschool children towards children's passive smoking, to show how attitudes influenced smoking and smoking behavior, and how the parents had experienced the handling of the tobacco issue in antenatal and child health care.

    Method

    A subsample of smoking and nonsmoking parents (n = 300) with 4- to 6-year-old children participating in All Babies in Southeast Sweden (ABIS), a prospective study on environmental factors affecting development of immune-mediated diseases, answered a questionnaire on their opinions and attitudes to children's passive smoking.

    Results

    Indoor smokers were more positive regarding smoking, less aware of the adverse health effects from passive smoking, and more negative regarding the handling of tobacco prevention in health care than both outdoor smokers and nonsmokers. Indoor smokers' idea of how children should be protected from tobacco smoke exposure was significantly different from the idea of nonsmokers and outdoor smokers.

    Discussion

    Results indicate that further intense efforts are needed to convince the remaining indoor smokers about the adverse health effects related to tobacco smoke exposure. Pediatric nurses meet these parents in their daily work and should be aware of the need to focus this group and their use of protective measures.

  • 225.
    Johansson, AnnaKarin
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Tobacco Exposure and Diabetes-Related Autoantibodies in Children Results from the ABIS Study2008In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1150, p. 197-199Article in journal (Refereed)
    Abstract [en]

    Passive smoking has decreased in recent years ("increased hygiene"). Less environmental tobacco smoke (ETS) gives increased hygiene that, if the hygiene hypothesis is true, in turn might give more autoimmune diseases. The presence of auto antibodies is considered to be an early indicator of type 1 diabetes (T1D). Because tobacco exposure may influence the immune system, we analyzed the relation between passive smoking and development of autoantibodies. A subsample (n = 8794) of the children in the ABIS study was used for this analysis. The parents answered questionnaires on smoking from pregnancy and onwards, and blood samples from the children aged 2.5-3 years were analyzed for GADA and IA-2A. Results showed that there was no significant difference in the prevalence of GADA or IA-2A (> 95 percentile) between tobacco-exposed and nonexposed children. It was concluded that passive smoking does not seem to influence development of diabetes-related autoantibodies early in life.

  • 226.
    Johansson, AnnaKarin
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    When does exposure of children to tobacco smoke become child abuse?2003In: The Lancet, ISSN 0140-6736, Vol. 361, no 9371, p. 1828-1828Article in journal (Refereed)
    Abstract [en]

    We report an instance of a child aged 2.5 years, who is exposed to tobacco smoke in the home. The child is a participant in a prospective cohort study (ABIS; all babies in southeast Sweden) we are undertaking, on environmental factors affecting development of immune-mediated diseases in children.1

    Exposure to environmental tobacco smoke, known to affect present and future health of children,2 is one of the environmental factors being studied. Parents are asked, in questionnaires, if and how much they smoke. A subsample of smoking parents of 2–3 year-old children has been asked about their smoking behaviour at home—ie, what precautions they use to protect their child from tobacco smoke. To validate this questionnaire, we have analysed urine cotinine concentrations (the major urinary metabolite of nicotine) in specimens provided by children of this age. We recorded that the smoking behaviour of parents at home was significantly associated with cotinine concentrations of their child. Cotinine concentrations were adjusted for creatinine.3

    The child we report here had a cotinine/creatinine ratio of 800 μg cotinine/1 g creatinine, corresponding to active smoking of 3–5 cigarettes a day.4 The parents reported a joint consumption of 41–60 cigarettes a day. They said they smoke in the kitchen and living room, whereas bedrooms were reported to be smoke-free. The parents reported smoking at the dinner table once a day and in front of the television set several times a day. They also said they smoke near the kitchen fan several times a day and near an open door at least once a week. These comments from the parents indicate that, in their opinion, their child was well protected from exposure to environmental tobacco smoke, since they did not smoke in bedrooms and the windows were almost always open.

    Though nicotine and cotinine metabolism is independent probably due to genetic differences,5 the cotinine concentration of this child is remarkably high. If active smoking in adults causes lung cancer and other serious diseases, passive smoking from the age of 2.5 years (and probably younger) must be even more deleterious. Since a child at this age cannot, by his or her own will, avoid a smoky environment, we ask ourselves when exposure to tobacco smoke should be regarded as child abuse?

    We want to stress the fact that, although most parents are aware of the importance of protecting their children from tobacco smoke, and try in different ways, children can still be massively exposed to this toxic drug. Since to just forbid smoking might be ineffective, nurses and doctors should pay attention to smoking behaviour of smoking parents they meet. Until we know more about effective measures of protection, the recommendation should be never to smoke indoors in homes with children.

  • 227.
    Johansson, AnnaKarin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Hermansson, Göran
    Adverse health effects related to tobacco smoke exposure in a cohort of three-year olds2008In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 97, no 3, p. 354-357Article in journal (Refereed)
    Abstract [en]

    Aim: To analyse the importance of mothers' smoking during pregnancy and/or environmental tobacco smoke (ETS) exposure in early childhood for children's health and well-being at the age of 3 years. Methods: Four groups from a population based cohort (n = 8850) were compared: children with nonsmoking mother during pregnancy and nonsmoking parents at the age of 3 years (n = 7091), children with only foetal exposure (n = 149), children exposed only postnatally (n = 895) and children exposed both pre- and postnatally (n = 595). Odds ratios and 95% confidence intervals were calculated. Results: Children exposed both pre- and postnatally had more wheezing (1.14, 1.07-1.21) and rhinitis (1.16, 1.06-1.26), used more cough-mixture (1.07, 1.01-1.14) and broncodilatating drugs (1.08, 1.02-1.15) and suffered more from excessive crying (1.31, 1.13-1.51) and irritability (1.27, 1.09-1.48) compared to children with nonsmoking parents. Children exposed only postnatally had more rhinitis (1.24, 1.12-1.37), used more cough-mixture (1.14, 1.05-1.29) and suffered more from poor sleep (1.26, 1.07-1.47) than children of nonsmoking parents. Children with prenatal exposure only used more broncodilatating drugs (1.45, 1.03-2.04) and suffered more from poor sleep (2.06, 1.09-3.87). Conclusion: Health differences, small but significant, indicate that prenatal and/or postnatal ETS exposure alone, or in combination, seems to interfere with child health, supporting the importance of zero tolerance. However, as most smoking parents in Sweden try to protect their children from ETS exposure, the results also might indicate that protective measures are worthwhile. © 2007 The Author(s).

  • 228.
    Jonsdottir, B
    et al.
    Lund University, Sweden .
    Andersson, C
    Lund University, Sweden .
    Carlsson, A
    Lund University, Sweden .
    Delli, A
    Lund University, Sweden .
    Forsander, G
    Karolinska Institute, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Marcus, C
    Karolinska Institute, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, E
    Karolinska Institute, Sweden .
    Lernmark, A
    Lund University, Sweden .
    Ivarsson, S-A
    Lund University, Sweden .
    Elding Larsson, H
    Lund University, Sweden .
    Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 8, p. 1735-1742Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.

  • 229.
    Jonson, Carl-Oscar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Lernmark, Åke
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Rutledge, Elizabeth A.
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Hinkkanen, Ari
    Department of Biochemistry and Pharmacy, Åbo Akademi, Turku, Finland.
    Faresjö, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    The importance of CTLA-4 polymorphism and Human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children2007In: Pediatric Diabetes, ISSN 1399-543X, Vol. 8, no 4, p. 185-192Article in journal (Refereed)
    Abstract [en]

    Background: Type 1 diabetes (T1D) is an autoimmune disease associated with the destruction of pancreatic β cells and genetically linked to human leukocyte antigen (HLA) class II DR3-DQ2 and DR4-DQ8 haplotypes. The +49A/G polymorphism of the immunoregulatory cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is also associated with T1D. Genetic and environmental risk factors precede the onset of T1D, which is characterized by a T helper 1 cell-dominating cytokine response to diabetes-related autoantigens.

    Aim: To investigate immunological differences between healthy children with and without CTLA-4 +49A/G and HLA genetic susceptibility for T1D.

    Study design: Young, 7–15 years of age, healthy subjects (n = 58) were investigated to test whether CTLA-4 +49A/G genotype was associated with enzyme-linked immunospot assay T-cell responses to T1D-related autoantigens. Because T1D is primarily HLA-DQ associated, we stratified the healthy subjects by HLA genotypes associated with the disease.

    Results: Peptide of heat shock protein 60 induced a higher interferon-γ (IFN-γ) response in subjects with risk-associated CTLA-4 polymorphism (GG genotype) (p = 0.02) while glutamic acid decarboxylase 65-induced interleukin-4 (IL-4) secretion was lower in GG genotype subjects (p = 0.02).

    Conclusion: The increased IFN-γ response and lower IL-4 response toward diabetes-related autoantigens shown in CTLA-4 +49 GG risk subjects show a possible mechanism for the association between CTLA-4 and T1D.

  • 230.
    Kajiura, M.
    et al.
    Department of Pediatrics, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, Japan.
    Tanaka, H.
    Department of Pediatrics, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, Japan.
    Borres, M.
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Thulesius, O.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Yamaguchi, H.
    Department of Pediatrics, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, Japan.
    Tamai, H.
    Department of Pediatrics, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, Japan.
    Variant autonomic regulation during active standing in Swedish and Japanese junior high school children2008In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 28, no 3, p. 174-181Article in journal (Refereed)
    Abstract [en]

    The present investigation is about cardiovascular responses and relevant autonomic function in Swedish and Japanese pubertal children on active standing using non-invasive continuous beat-to-beat finger arterial pressure (FAP) monitoring and power spectral analysis. Examined were 54 Swedish and 57 Japanese children (13-15 years). FAP and heart rate (HR) was continuously recorded in the supine position and during standing. Supine FAP was significantly higher in Swedish compared with Japanese children (121/62 versus 103/53 mmHg, P < 0.001). Swedish children showed a higher increase in arterial pressure and HR upon uprising, resulting in a higher vasoconstrictor index (5.04 ± 0.22 versus 2.31 ± 0.11 mmHgs-1, P < 0.001, respectively). There were also higher increases in arterial pressure and HR in the following steady state period (1-7min) between the two groups. These differences were also found after adjustment of body weight and height. Frequency domain analysis of HR and arterial pressure variability indicated significantly higher low/high frequency power of HR and low frequency power of arterial pressure. These results suggest that Swedish pubertal children have higher basal blood pressure and enhanced cardiovascular sympathetic responses. These differences in the two cohorts might be caused by genetic factors. © 2008 The Authors Journal compilation © 2008 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  • 231.
    Kallen, A J Bengt
    et al.
    Tornblad Institute, University of Lund.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, Anna P
    Department of Statistics, Monitoring and Analyses, National Board of Health and Welfare, Stockholm.
    Nilsson, Emma M E
    Department of Statistics, Monitoring and Analyses, National Board of Health and Welfare, Stockholm.
    Nygren, Karl-Gösta
    IVF and Fertility Clinic, Sophiahemmet, Stockholm.
    Otterblad Olausson, Petra M
    Department of Statistics, Monitoring and Analyses, National Board of Health and Welfare, Stockholm.
    Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?2011In: EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY, ISSN 1090-3798, Vol. 15, no 3, p. 247-253Article in journal (Refereed)
    Abstract [en]

    Background: There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. Aim: To investigate the risk for ADHD in children conceived after IVF. Methods: Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel-Haenszel procedures. We studied 28158 children born after IVF and compared them with 2417886 children in the population. Results: After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio = 1.18, 95% confidence interval 1.03-1.36. The effect was stronger in girls (OR = 1.40) than boys (OR = 1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. Conclusions: The study suggests a weak association between IVF and drug treated ADHD.

  • 232.
    Kallen, B
    et al.
    Lund University.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, A
    Board of Health and Welfare, Stockholm, Sweden .
    Nilsson, E
    Board of Health and Welfare, Stockholm, Sweden .
    Nygren, K-G
    IVF and Fertil Clin, Stockholm, Sweden .
    Otterblad Olausson, P
    Board of Health and Welfare, Stockholm, Sweden .
    Malignancies among women who gave birth after in vitro fertilization2011In: HUMAN REPRODUCTION, ISSN 0268-1161, Vol. 26, no 1, p. 253-258Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Relatively few studies published to date have investigated IVF and cancer risk. In this study we compared the occurrence of cancer in women who gave birth after IVF with all other women who gave birth in the study period. METHODS: All women who were treated with IVF and gave birth during the years 1982-2006 in Sweden were identified from all IVF clinics, and the occurrence of cancer in these women was identified by linkage with the nationwide Swedish cancer register. Comparison was made with Mantel-Haenszel odds ratios (ORs), adjusting for year of delivery and maternal age, parity and smoking. Cancer before IVF was only studied in first parity women. Specific cancer forms were also studied. RESULTS: Among 24 058 women who had been treated with IVF, 1279 appeared in the cancer register. The total number of women studied in the population was 1 394 061, and 95 775 of these were registered in the cancer register. The risk for cancer before IVF was increased [OR 1.37, 95% confidence interval (CI) 1.27-1.48] and was especially high for ovarian cancer (3.93). The risk for cancer after IVF was significantly lower (OR 0.74, 95% CI 0.67-0.82), mainly due to a lower than expected risk for breast and cervical cancer. The risk for ovarian cancer was increased but lower than the risk before IVF (2.13). CONCLUSIONS: Cancer or cancer treatment may increase the risk for infertility leading to IVF. After IVF, in most cases with treatment with fertility hormones, a significantly low cancer risk was found. Ovarian cancer showed an increased risk, although lower than before IVF. One possible reason is ovarian pathology causing both infertility and an increased cancer risk.

  • 233.
    Kallen, B
    et al.
    Lund University.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, A
    National Board for Health and Welfare, Stockholm.
    Nilsson, E
    National Board for Health and Welfare, Stockholm.
    Nygren, K-G
    IVF and Fertil Clin, Stockholm.
    Otterblad Olausson, P
    National Board for Health and Welfare, Stockholm.
    Selected neonatal outcomes in dizygotic twins after IVF versus non-IVF pregnancies2010In: BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, ISSN 1470-0328, Vol. 117, no 6, p. 676-682Article in journal (Refereed)
    Abstract [en]

    Objective To compare neonatal outcome among twins conceived after in vitro fertilisation (IVF) with that of spontaneously conceived twins. Design Comparison of different-sex (dizygotic) twins born after IVF with non-IVF dizygotic twins. Setting National health registers in Sweden. Population All births in Sweden during the period 1982-2007. Methods We studied gestational duration, lowest birthweight and birthweight difference in the twin pair, presence of one or two twins with a respiratory complication, and with jaundice in one or both twins. Risk estimates were calculated as odds ratios with adjustments for year of birth, maternal age, parity and smoking in pregnancy. Main outcome measures Gestational duration, birth weight, respiratory complications, jaundice. Results We studied 1545 pairs of dizygotic twins born after IVF, and 8675 pairs of dizygotic twins where IVF was not known to have occurred. The risk for preterm delivery before 32 weeks of gestation was significantly increased among dizygotic twin pairs born after IVF compared with non-IVF dizygotic twin pairs. No significant difference in low birthweight or birthweight difference within twin pairs was seen. There was an increased occurrence of twin pairs with respiratory problems or jaundice, but only the latter diagnosis occurred in a statistically significant excess. Conclusions The study confirms recent findings that IVF is associated with an increased risk for some neonatal complications, not only among singletons but also among twins.

  • 234.
    Kallen, B
    et al.
    Lund University.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, A
    National Board for Health and Welfare, Sweden .
    Nilsson, E
    National Board for Health and Welfare, Sweden .
    Nygren, K-G
    IVF and Fertility Clinic, Sweden .
    Otterblad Olausson, P
    National Board for Health and Welfare, Sweden .
    Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years2010In: HUMAN REPRODUCTION, ISSN 0268-1161, Vol. 25, no 4, p. 1026-1034Article in journal (Refereed)
    Abstract [en]

    Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment. This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred. There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little. The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.

  • 235.
    Kallen, Bengt
    et al.
    Lund University.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, Anna
    National Board for Health and Welfare, Stockholm.
    Nilsson, Emma
    National Board for Health and Welfare, Stockholm.
    Nygren, Karl-Gosta
    IVF and Fertil Clinic, Stockholm.
    Olausson Otterblad, Petra
    National Board for Health and Welfare, Stockholm.
    Congenital Malformations in Infants Born after In Vitro Fertilization in Sweden2010In: BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, ISSN 1542-0752, Vol. 88, no 3, p. 137-143Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The risk for congenital malformations is increased in infants born after in vitro fertilization (IVF). Some specific malformations appear to be more affected than others. METHODS: The presence of congenital malformations in 15,570 infants born after IVF with an embryo transfer between April 1, 2001, and the end of 2006 were compared with all infants born in Sweden during 2001 to 2007 (n = 689,157). Risk estimates were made after adjusting for year of birth, maternal age, parity, smoking, and body mass index. The risks of specific malformations were compared with data from a previous study (1982 to March 31, 2001) of 16,280 infants born after IVF. Different IVF methods were compared to respect to malformation risk. RESULTS: Increased risks of a similar magnitude were found for most cardiovascular malformations and limb reduction defects for both study periods. For neural tube defects, cardiac septal defects, and esophageal atresia, there was still an increased risk, but it was lower during the second than during the first period. For small bowel atresia, anal atresia, and hypospadias, the risk increase observed during the first study period had disappeared during the second period. An increased risk was seen for some syndromes that have been associated with imprinting errors. No difference in malformation risk according to IVF method was apparent. CONCLUSIONS: A slightly increased risk for congenital malformations after IVF persists. A decreasing risk is seen for some specific malformations, either true or the result of multiple testing.

  • 236.
    Kallen, Bengt
    et al.
    Lund University.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, Anna
    National Board for Health and Welfare, Stockholm, Sweden .
    Nilsson, Emma
    National Board for Health and Welfare, Stockholm, Sweden .
    Nygren, Karl-Gosta
    Sophiahemmet.
    Otterblad Olausson, Petra
    National Board for Health and Welfare, Stockholm, Sweden .
    Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?2010In: FERTILITY AND STERILITY, ISSN 0015-0282, Vol. 94, no 5, p. 1680-1683Article in journal (Refereed)
    Abstract [en]

    Objective: To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF. Design: Register study. Setting: Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006. Patient(s): Treatments reported from all Swedish IVF clinics. Intervention(s): None. Main Outcome Measure(s): Some neonatal characteristics were compared in 1,311 infants born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687). Result(s): After adjusting for year of birth, maternal age, parity, smoking habits, and body mass index, the risk of preterm birth among singletons was significantly greater after blastocyst-stage transfer than after cleavage-stage transfer. The risk of congenital malformations was also significantly higher. When the analysis was restricted to clinics where blastocyst transfers were made, the risk estimates increased for preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but did not change for congenital malformations. Conclusion(s): The results indicate a small increase in risk associated with blastocyst transfer, perhaps owing to the longer period of in vitro culture. There is a possibility that this effect is due, at least in part, to a selection of women for blastocyst transfers. Further studies are needed either to verify or to refute the found associations.

  • 237.
    Kallen, Bengt
    et al.
    Lund University.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindam, Anna
    National Board of Health and Welfare, Stockholm, Sweden .
    Nilsson, Emma
    National Board of Health and Welfare, Stockholm, Sweden .
    Nygren, Karl-Gosta
    IVF and Fertil Clin, Stockholm, Sweden .
    Otterblad Olausson, Petra
    National Board of Health and Welfare, Stockholm, Sweden .
    Cancer Risk in Children and Young Adults Conceived by In Vitro Fertilization2010In: PEDIATRICS, ISSN 0031-4005, Vol. 126, no 2, p. E270-E276Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Studies conducted so far have found no statistically significant increased risk for cancer among children who are born after in vitro fertilization (IVF). METHODS: We followed 26 692 children who were born after IVF during the years 1982-2005 by using the Swedish Cancer Register and compared the number of children who had cancer and were born after IVF with children who were not conceived by IVF. Adjustment was made for year of birth. RESULTS: Maternal age, parity, smoking, subfertility, previous miscarriages, BMI, and multiple births did not significantly affect cancer risk in offspring. High birth weight, premature delivery, and the presence of respiratory diagnoses and low Apgar score were risk factors for cancer. We identified 53 cases of cancer in children who were born after IVF against 38 expected cases: 18 of them with hematologic cancer (15 of them acute lymphoblastic leukemia), 17 with eye or central nervous system tumors, and 12 with other solid cancers. There were 6 cases of Langerhans histiocytosis against 1.0 expected. The total cancer risk estimate was 1.42 (95% confidence interval: 1.09-1.87). CONCLUSIONS: We found a moderately increased risk for cancer in children who were conceived by IVF. Putative intermediary factors could be preterm birth and neonatal asphyxia.

  • 238.
    Kallen, Bengt
    et al.
    Lund University, Sweden .
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nygren, Karl-Gosta
    IVF and Fertil Clin, Sweden .
    Otterblad Olausson, Petra
    National Board Health and Welf, Sweden .
    Association between preterm birth and intrauterine growth retardation and child asthma2013In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 41, no 3, p. 671-676Article in journal (Refereed)
    Abstract [en]

    An association between preterm birth and an increased risk of childhood asthma has been demonstrated, but the importance of intrauterine growth retardation on asthma risk is unclear. less thanbrgreater than less thanbrgreater thanUsing data from Swedish health registers, infant characteristics and childhood asthma were studied. Analyses were made using Mantel-Haenszel methodology with adjustment for year of birth, maternal age, parity, smoking in early pregnancy and maternal body mass index. Preterm birth, birth weight and birth weight for gestational week were analysed and childhood asthma was evaluated from prescriptions of anti-asthmatic drugs. Neonatal respiratory problems and treatment for them were studied as mediating factors. less thanbrgreater than less thanbrgreater thanBoth short gestational duration and intrauterine growth retardation appeared to be risk factors and seemed to act separately. The largest effect was seen from short gestational duration. Use of mechanical ventilation in the newborn period and bronchopulmonary dysplasia were strong risk factors. A moderately increased risk was also seen in infants born large for gestational age. less thanbrgreater than less thanbrgreater thanWe conclude that preterm birth is a stronger risk factor for childhood asthma than intrauterine growth disturbances; however, the latter also affects the risk, and is also seen in infants born at term.

  • 239.
    Kallen, Bengt
    et al.
    Lund University, Sweden .
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nygren, Karl-Gosta
    Karolinska Institute, Sweden .
    Otterblad Olausson, Petra
    National Board Health and Welf, Sweden .
    Asthma in Swedish children conceived by in vitro fertilisation2013In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, Vol. 98, no 2, p. 92-96Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate a proposed association between in vitro fertilisation (IVF) and child asthma. less thanbrgreater than less thanbrgreater thanDesign The risk for asthma after IVF was estimated as ORs using Mantel-Haenszel analysis. less thanbrgreater than less thanbrgreater thanSetting The Swedish Medical Birth Register. less thanbrgreater than less thanbrgreater thanPatients Of the 2 628 728 children born in 1982-2007 and surviving the perinatal period, 31 918 were conceived by IVF. Presence of asthma was defined as at least five prescriptions of antiasthmatic drugs during the period 1 July 2005-31 December 2009 according to the Swedish Prescribed Drug Register (115 767 children, 2323 of whom were born after IVF). less thanbrgreater than less thanbrgreater thanResults A significantly increased risk for asthma, albeit small, was found in children conceived by IVF (aOR 1.28, 95% CI 1.23 to 1.34), increasing the absolute risk from 4.4% to 5.6%. The risk increase for asthma was the same in boys and girls, in singletons and twins, and after caesarean section and vaginal delivery. The risk was higher for preterm than term singletons. For children with a low Apgar score, respiratory diagnoses, mechanical ventilation, continuous positive airway pressure or neonatal sepsis, the effect of IVF on asthma risk was low and statistically non-significant. Adjustment for length of involuntary childlessness eliminated the effect, and removal of infants whose mothers had used antiasthmatics in early pregnancy reduced the risk. less thanbrgreater than less thanbrgreater thanConclusions This study verifies an association between IVF and asthma in children. This can be partly explained by neonatal morbidity and by maternal asthma acting as mediators, but the main risk factor is parental subfertility. The mechanism for this is unclear.

  • 240.
    Kallen, Bengt
    et al.
    Lund University, Sweden .
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Nygren, Karl-Gosta
    Karolinska Institute, Sweden .
    Otterblad Olausson, Petra
    National Board Health and Welf, Sweden .
    Maternal and fetal factors which affect fetometry: use of in vitro fertilization and birth register data2013In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 170, no 2, p. 372-376Article in journal (Refereed)
    Abstract [en]

    Background: Fetometry dating of gestational age is the gold standard in most developed countries but may have some inborn errors. Dating pregnancies after in vitro fertilization can be used for the evaluation of fetometric studies and for studies of variables which may affect them. less thanbrgreater than less thanbrgreater thanMethods: We compared the actual gestational age of 9543 singleton and 869 twin pregnancies with estimates based on second-trimester fetometry. Mean gestational age, percentage of births classified as preterm, and skewness of the distribution of differences between actual and estimated gestational age were studied. Subanalyses were made of data on singletons for males and females, for infants born to overweight or obese women or to smoking women, for infants judged to be small or large for gestational age, and on twins. less thanbrgreater than less thanbrgreater thanResults: In the majority of cases, good agreement was found between actual and estimated gestational age but in singletons there was an excess of positive differences resulting in a moderate over-estimate of the rate of preterm births (8%), more marked for females (11%) than for males (6%) and increased for infants born to overweight (7%) or obese (16%) mothers. Singleton infants born small for gestational age also showed an excess of positive differences (3%). These differences were less marked for twins. less thanbrgreater than less thanbrgreater thanConclusions: In most IVF pregnancies, routine fetometry correctly predicts gestational age but deviations exist which indicate that ultrasound underestimates the age of fetuses that will be born small for gestational age and when the woman is obese. The differences between actual age and estimates based on fetometry seem to be smaller than those between estimates based on last menstrual period and fetometry.

  • 241.
    Kallen, Bengt
    et al.
    Lund University, Sweden .
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nygren, Karl-Gosta
    Karolinska Institute, Sweden .
    Otterblad Olausson, Petra
    National Board Health and Welf, Sweden .
    Maternal drug use during pregnancy and asthma risk among children2013In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 1, p. 28-32Article in journal (Refereed)
    Abstract [en]

    Background Maternal use of some drugs, notably paracetamol and drugs for gastroesophageal reflux, has been associated with an increased risk of childhood asthma in the child. We wanted to analyze these associations with consideration to the confounding of maternal asthma. Methods Childhood asthma was identified from the Swedish National Prescription Register and maternal drug use during the latter part of pregnancy from antenatal records, computerized in the Swedish Medical Birth Register. Risks were estimated as odds ratios (OR) with 95% confidence intervals, using MantelHaenszel technique with adjustment for year of birth, maternal age, parity, smoking habits, and BMI. Results A statistical association between maternal use of many different drugs, including paracetamol, and childhood asthma existed but was mainly due to concomitant drug use, related to maternal asthma. The only associations that appeared to be true were with drugs for gastroesophageal reflux (adjusted (OR) = 1.32, 95% CI, 1.181.54) and with opiates (adjusted OR = 1.56 (96% CI, 1.052.34). Conclusions Maternal use of paracetamol did not seem to increase the risk of childhood asthma, but the previously described association with drugs for gastroesophageal reflux was supported. The analysis is complicated by the confounding from maternal asthma.

  • 242.
    Karlén, Jerker
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Could the social environment trigger the induction of diabetes related autoantibodies in young children?2012In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 40, no 2, p. 177-182Article in journal (Refereed)
    Abstract [en]

    Aims: The onset and progression of the autoimmune process leading to type 1 diabetes is partly dependent on genetic predisposition and partly on environmental factors. We have implemented a study design where 1-year-old children, from two equally sized, neighbouring but socioeconomically different cities, were compared for the induction of beta-cell autoantibodies. Methods: This study comprises 2448 newborn infants, all living in the urban parts of the twin cities, followed prospectively with regular biological samples and questionnaires in a major population-based study. Of these, a random sample of 1497 children were tested for tyrosine phosphatase (IA-2A) and 1409 children for glutamic acid decarboxylase (GADA). Other documented risk factors of beta-cell autoimmunity and type 1 diabetes, such as family characteristics, dietary factors, and psychosocial factors were also included in the analysis. Results: The risk for diabetes-related autoantibodies, both against GADA and IA-2A (andgt; 95% cut off), was significantly higher (p andlt; 0.0001) among children from the blue-collar than from the white-collar city. This difference persisted still after adjustment for other previously documented risk factors. Some of these previously known risk factors remained significant in the multivariate analysis as independent explanatory factors, in addition to living in a blue-collar city. Conclusions:Factors in the social environment could trigger the induction of diabetes-related autoantibodies in 1-year-old children. These results point out that our present knowledge of factors influencing the autoimmune process might be widen to also include factors in the social environment of the community.

  • 243.
    Karlén, Jerker
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Frostell, Anneli
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Maternal Influence on Child HPA Axis: A Prospective Study of Cortisol Levels in Hair2013In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 132, no 5, p. E1333-E1340Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate cortisol concentrations in hair as biomarker of prolonged stress in young children and their mothers and the relation to perinatal and sociodemographic factors. less thanbrgreater than less thanbrgreater thanMETHODS: Prospective cohort study of 100 All Babies In Southeast Sweden study participants with repeated measures at 1, 3, 5, and 8 years and their mothers during pregnancy. Prolonged stress levels were assessed through cortisol in hair. A questionnaire covered perinatal and sociodemographic factors during the childs first year of life. less thanbrgreater than less thanbrgreater thanRESULTS: Maternal hair cortisol during the second and third trimester and child hair cortisol at year 1 and 3 correlated. Child cortisol in hair levels decreased over time and correlated to each succeeding age, between years 1 and 3 (r = 0.30, P = .002), 3 and 5 (r = 0.39, P andlt; .001), and 5 and 8 (r = 0.44, P andlt; .001). Repeated measures gave a significant linear association over time (P andlt; .001). There was an association between high levels of hair cortisol and birth weight (beta = .224, P = .020), nonappropriate size for gestational age (beta = .231, P = .017), and living in an apartment compared with a house (beta = .200, P = .049). In addition, we found high levels of cortisol in hair related to other factors associated with psychosocial stress exposure. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: Correlation between hair cortisol levels in mothers and their children suggests a heritable trait or maternal calibration of the childs hypothalamic-pituitary-adrenocortical axis. Cortisol output gradually stabilizes and seems to have a stable trait. Cortisol concentration in hair has the potential to become a biomarker of prolonged stress, especially applicable as a noninvasive method when studying how stress influences childrens health.

  • 244.
    Karlén, Jerker
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Lowert, Yvonne
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Chatziarsenis, KM
    Clinic of Social and Family Medicine, School of Medicine, University of Crete, Greece.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Are children from Crete abandoning a Mediterranean diet?2008In: Rural and remote health, ISSN 1445-6354, Vol. 8, no 4, p. 1034-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Mediterranean countries such as Greece have experienced rapid social change in the last decade. These community changes affect nutritional habits and there is a tendency for the traditional healthy Mediterranean diet to be abandoned.

    METHODS:

    The parents of children from one rural Greek village on Crete (Neapolis), and one rural village in Sweden (Kisa) were invited to their primary health care centers for an interview and to fill in a validated nutrition questionnaire, KidMed.

    RESULTS:

    There were no differences (p = 0.48) in total KidMed score between the Cretan and Swedish children, adjusted for gender and age. However, there were some significant differences in scores on certain KidMed questions. Parents of the Cretan children reported significantly higher daily use of olive oil at home and more regular nut consumption, but also more commercially baked goods or pastries for breakfast. The parents of Swedish children reported significantly higher use of cereals, grains or bread for breakfast. The mean BMIs were similar for the Cretan (Neapolis mean 16.8, 95% CI 13.5-23.0) and for the Swedish children (Kisa mean 17.4, 95% CI 13.7-25.5)

    CONCLUSION:

    The results suggest the possibility of changing nutritional habits, measurable among young children in rural areas. The study raises the question of whether Cretan children may have abandoned some aspects of the traditional Mediterranean diet. It may also be that Swedish children have changed their diet in favor of a more Mediterranean food choice. The major limitation of the study is the small sample size, and further, larger studies are warranted.

  • 245.
    Karlén, Jerker
    et al.
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Frostell, Anneli
    Linköping University, Department of Behavioural Sciences and Learning, Cognition, Development and Disability. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Cortisol in hair measured in young adults - a biomarker of major life stressors?2011In: BMC Clinical Pathology, ISSN 1472-6890, E-ISSN 1472-6890, Vol. 11, no 1, p. 12-Article in journal (Refereed)
    Abstract [en]

    Background Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults. Methods Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised. Results Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems. Conclusions These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.

  • 246.
    Karlén, Jerker
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Hedmark, Max
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Impact of prenatal psychosocial exposures on hair cortisol levels and child health: cohort study2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background Early psychosocial exposures are increasingly recognized as crucial for health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker, assessing long-term HPA axis activity. The objective was to investigate whether prenatal adverse psychosocial circumstances influence infant cortisol levels in hair and health outcome in children prospectively until age 10.

    Methods True prospective cohort study in the general community with a questionnaire covering 11 psychosocial items in the family during pregnancy formed a composite scale of prenatal psychosocial vulnerability, and cumulative incidence of diseases through diagnoses until age 10 in n=1876 children. At age 1, cortisol levels in hair were measured using a competitive radioimmunoassay on a subsample of n=209.

    Results Children with added prenatal psychosocial exposures had higher infant cortisol levels in hair (B=0.40, p<0.0001, adjusted for gender and size for gestational age) in a cumulative manner and were more often (p≤0.05) affected by 12 of the 14 most common childhood diagnoses with a general pattern of rising ORs.

    Conclusions These findings support the model of physiologic dysregulation as a plausible mechanism in how the duration and number of early detrimental psychosocial exposures determine health outcome. It indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance.

  • 247.
    Kivling, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Sollvander, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Johanson, Calle
    Ryhov Jonkoping City Hospital.
    Faresjö, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Diverse FOXP3 Expression in Children with Type 1 Diabetes and Celiac Disease2008In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1150, p. 273-277Article in journal (Refereed)
    Abstract [en]

    Imbalance between different types of T lymphocytes, such as T helper (Th) and regulatory T cells (Tregs), has been reported to play a part in the pathogenesis behind such autoimmune diseases as type 1 diabetes (T1D) and celiac disease (CD). Defects in Tregs are proposed to at least partly explain the imbalance of Th cells found in children with immunologic diseases. Peripheral blood mononuclear cells from 24 children with T1D and/or CD, and reference children (that is, those without any of these diseases) were stimulated with disease-associated antigens (insulin, gluten, transglutaminase [tTG]), and phytohemagglutinin (PHA). The mRNA expression of the Treg-associated marker FOXP3 was analyzed with multiplex real-time RT-PCR. Children with T1D showed both a low spontaneous (P < 0.05) and PHA-induced (P < 0.01) expression of FOXP3 mRNA compared to children with CD. Children with T1D also had a low PHA-induced FOXP3 mRNA expression compared to the group of children diagnosed with both T1D and CD (P < 0.05). Spontaneous (P < 0.05) and PHA-induced (P < 0.05) FOXP3 mRNA expression was high in children with CD compared to reference children. In contrast, stimulation with insulin tended to induce high FOXP3 mRNA expression in T1D children compared to reference children (P = 0.057). In conclusion, children with only T1D generally showed a lower FOXP3 mRNA expression than did children with CD, or with T1D in combination with CD, which suggests impaired regulation of the immune system in children with T1D.

  • 248.
    Kivling, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Åkesson, Karin
    Clinic of Paediatrics, Ryhov County Hospital, Jönköping, Sweden 4.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Faresjö, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Diverging immune responses when allergy, type 1 diabetes and celiac disease coexistManuscript (preprint) (Other academic)
    Abstract [en]

    An imbalance between different immune cells, among them T-cells and inflammatory cells, has been proposed to be part of the disease process in type 1 diabetes (T1D), celiac disease and allergy. T-cells and inflammatory cells exert their actions through cytokines and chemokines, and the secretion of those can be used to describe the cell milieu during an immune response.

    This study included seventy-two children, diagnosed with T1D, celiac disease, allergy, or a combination of two of these diseases and compared to reference children. The study aimed to evaluate the secretion of 27 different cytokines and chemokines in cell culture supernatant after in vitro stimulation with disease-associated antigens (birch, gluten, insulin) detected by Luminex technique.

    Combination of allergy with either T1D or celiac disease gave diverging results. Children with combination of T1D and allergy showed an increased secretion of several cytokines (IL-2, IL-4, IL-5, IL-7, IL-9, IL-10, IL-12, IL-15, IL-17 and CCL11), in comparison to almost all groups from birch stimulation. In contrast, when allergy was combined with celiac disease, the spontaneous secretion of IL-1β, IL-5, IL-6, IL-9, IL-10, IL-12 and CCL3 was decreased compared to children with T1D or allergy, as well as children with celiac disease alone, children with combination of T1D and allergy and reference children.

    In conclusion, our results shed some light on the immune responses in children with common immunological diseases. Our study indicates diverging immune responses when allergy, type 1 diabetes and celiac disease coexist.

  • 249.
    Kivling, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Åkesson, Karin
    Clinic of Paediatrics, Ryhov County Hospital, Jönköping, Sweden 4.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Faresjö, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Combined type 1 diabetes and celiac disease in children give raise to a pronounced Treg populationManuscript (preprint) (Other academic)
    Abstract [en]

    Regulatory T-cells (Treg) suppress the immune response in order to avoid harmful effects. A wide range of highly expressed markers are associated to Treg, among them are CD4, CD25, CD39 and forkhead box p3 (FOXP3). Others are expressed in a low number on Tregs, for example CD45RA and CD127. Type 1 diabetes (T1D) and celiac disease are both autoimmune diseases, caused by an unwanted immune response, and Treg cells have been associated to both diseases. As T1D and celiac disease share same risk genes, patients have the risk of developing the other disease subsequently. Treg cells have been implicated to be associated with development of T1D combined with celiac disease.

    This pilot study aimed to investigate the expression of Treg associated markers in both CD4+CD25+ and CD4+CD25high cells by flow cytometry. In order to evaluate the involvement of Treg cells, CD39, CD45RA, CD127 and FOXP3 were studied in children with combination of T1D and celiac disease, in comparison to children with either T1D or celiac disease, and healthy children.

    Our data point out that children with combination of T1D and celiac disease have higher expression of FOXP3 as well as CD39, together with a decreased expression of both CD127 and CD45RA, in comparison to children with exclusively T1D or celiac disease. Even though none of the groups differed from the reference group, our data indicates that children with combination of T1D and celiac disease have a more pronounced Treg population, both in frequency and MFI, compared to children with either T1D or celiac disease.

  • 250.
    Kjellman, Britt-Marie
    et al.
    Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Glad Mattsson, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Huss, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Comparing ambient, air-convection, and fluid-convection heating techniques in treating hypothermic burn patients, a clinical RCT2011In: Annals of Surgical Innovation and Research, ISSN 1750-1164, Vol. 5Article in journal (Refereed)
    Abstract [en]

    Background: Hypothermia in burns is common and increases morbidity and mortality. Several methods are available to reach and maintain normal core body temperature, but have not yet been evaluated in critical care for burned patients. Our units ordinary technique for controlling body temperature (Bair Hugger®+ radiator ceiling + bed warmer + Hotline®) has many drawbacks e.g.; slow and the working environment is hampered.The aim of this study was to compare our ordinary heating technique with newly-developed methods: the Allon™2001 Thermowrap (a temperature regulating water-mattress), and Warmcloud (a temperature regulating air-mattress).Methods: Ten consecutive burned patients (andgt; 20% total burned surface area and a core temperature andlt; 36.0C) were included in this prospective, randomised, comparative study. Patients were randomly exposed to 3 heating methods. Each treatment/measuring-cycle lasted for 6 hours. Each heating method was assessed for 2 hours according to a randomised timetable. Core temperature was measured using an indwelling (bladder) thermistor. Paired t-tests were used to assess the significance of differences between the treatments within the patients. ANOVA was used to assess the differences in temperature from the first to the last measurement among all treatments. Three-way ANOVA with the Tukey HSD post hoc test and a repeated measures ANOVA was used in the same manner, but included information about patients and treatment/measuring-cycles to control for potential confounding. Data are presented as mean (SD) and (range). Probabilities of less than 0.05 were accepted as significant.Results: The mean increase, 1.4 (SD 0.6C; range 0.6-2.6C) in core temperature/treatment/measuring-cycle highly significantly favoured the Allon™2001 Thermowrap in contrast to the conventional method 0.2 (0.6)C (range -1.2 to 1.5C) and the Warmcloud 0.3 (0.4)C (range -0.4 to 0.9C). The procedures for using the Allon™2001 Thermowrap were experienced to be more comfortable and straightforward than the conventional method or the Warmcloud.Conclusions: The Allon™2001 Thermowrap was more effective than the Warmcloud or the conventional method in controlling patients temperatures. © 2011 Kjellman et al; licensee BioMed Central Ltd.

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