F1000 - Post-publication peer review of the biomedical literature, 2013
Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac... more Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an illdefined component of innate immunity in celiac disease. We identify the -amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4-MD2-CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients' biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.
Background: An association between cow's milk hypersensitivity (CMH) and gastro-oesophageal reflu... more Background: An association between cow's milk hypersensitivity (CMH) and gastro-oesophageal reflux disease (GERD) in childhood has been reported in the past decade. Aim: To assess whether biopsies from the upper gastrointestinal tract of children with cow's milk sensitive GERD have a specific allergic inflammatory pattern, and to compare two different techniques for measuring inflammatory cells in gastrointestinal biopsies. Methods: GERD was diagnosed by means of endoscopy and oesophageal pH monitoring. Hypersensitivity to cow's milk was determined by an elimination diet and cow's milk challenge. Allergic inflammatory cells in upper gastrointestinal biopsies were identified by immunohistochemistry and their numbers were assessed by two different methods-counting the number of cells/high power field and using the computerised Cast-Grid system. Results: Cow's milk sensitive GERD was identified in 10 of 17 children with severe GERD (median age, 7.8 years). Biopsies from children with endoscopic oesophagitis had significantly increased numbers of mast cells and T cells. No differences in the number of eosinophils, mast cells, or T cells were found between children with CMH and those with primary GERD. Several differences were found between the two different histological quantification methods. Conclusions: CMH was found not only in infants but also in school age children with GERD. Histology did not identify the cow's milk sensitive GERD subgroup. The computerised histological method provides a more complete evaluation based upon total biopsy area, and helped to limit the bias of uneven biopsy size.
This thesis is based on 9 papers on the uptake of dietary antigens and on the humoral immune resp... more This thesis is based on 9 papers on the uptake of dietary antigens and on the humoral immune responses to dietary antigens, in healthy subjects and in patients with coeliac disease or atopic eczema. Work in experimental animals have indicated that dietary antigens are taken up in amounts, which are nutritionally insignificant, but may be of immunological importance. Local or systemic antibodies may retard the uptake, but in addition may increase the uptake of unrelated antigens. In humans the uptake of intact dietary antigen, free or in immune complexes, was reported in studies in healthy subjects and in patients with immune deficiency or atopy. We investigated the uptake of dietary antigen in 8 healthy subjects after a test meal, using ELISA methods and high performance liquid chromatography (HPLC) for the fractionation of serum samples. A significant finding was that ovalbumin (OA) was taken up as intact antigen or as a high MW immune complex constituent in all the 8 subjects. IgG...
Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians... more Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, HLA genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/ undetectable,anIgG-basedtest is indicated.Patientswithpositiveresultsshould...
Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive de... more Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive development in early childhood and increased incidence of infections; however, the longitudinal association between early-life factors and ID in 18-month-old children in Denmark is unknown. The present study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort. The questionnaires were modified from those used in the Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of seventy-nine children due to chronic disease, acute infection, C-reactive protein >10 mg/l, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for ...
Introduction Many aspects of the management of esophageal atresia (EA) and tracheoesophageal fist... more Introduction Many aspects of the management of esophageal atresia (EA) and tracheoesophageal fistula (TEF) are controversial and the evidence for decision making is limited. Members of the European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) conducted a consensus conference on the surgical management of EA/TEF based on expert opinions referring to the latest literature. Materials and Methods Nineteen ERNICA representatives from nine European countries participated in the conference. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing the domains diagnostics, preoperative, operative, and postoperative management, and literature review. The 2-day conference was held in Berlin in October 2018. Anonymous voting was conducted via an internet-based system. Consensus was defined when 75% of the votes scored 6 to 9. Results Fifty-two items were generated with 116 relevant articles of which five s...
Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into ad... more Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into adulthood, and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in breast milk have been suggested as mediators of the beneficial long-term effect of breastfeeding on BP and BLP. We aimed to investigate associations between n-3 LC-PUFA content in breast milk at 4 months postpartum and offspring BP and BLP in early life. BP and BLP were measured at 4, 18, and 36 months. Statistical analyses were sex-stratified and adjusted for gestational age, maternal pre-pregnancy body mass index (BMI), and maternal educational level. Based on 336 mother-child dyads, high n-3 LC-PUFA in breast milk was inversely associated with systolic and diastolic BP in boys at 4 months (β = −20.0 (95% CI = −33.4, −6.7), p = 0.004 and β = −10.2 (95% CI = −19.8, −0.5), p = 0.039, respectively); inversely associated with HDL cholesterol, and directly associated with triglyceride in girls at 4 months (β = −0.7 (95% C...
Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoyleth... more Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA), which induce satiety through endogenous formation in the small intestine upon feeding, but also when orally or systemic administered. OEA, SEA, and PEA are present in human milk, and we hypothesized that the content of OEA, SEA, and PEA in mother’s milk differed for infants being heavy (high weight-for-age Z-score (WAZ)) or light (low WAZ) at time of milk sample collection. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of OEA, SEA, and PEA in milk samples collected four months postpartum from mothers to high (n = 50) or low (n = 50) WAZ infants. Associations between OEA, SEA, and PEA concentration and infant anthropometry at four months of age as well as growth from birth were investigated using linear and logistic regression analyses, adjusted for birth ...
Introduction: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that... more Introduction: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that have resulted in global environmental exposures. Previous epidemiological studies have reported possible effects on the immune system after developmental PFAS exposure, but the possible impact on childhood infectious disease is unclear. Objectives: To investigate the association between prenatal exposure to PFAS and symptoms of infections at age 1-4 years. Methods: The Odense Child Cohort is an ongoing prospective study on children's health, where serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in 649 pregnant women before gestational week 16. Of these women, 359 reported on symptoms of infection in their child every two weeks for a one-year period. The association between prenatal exposure to PFAS and the symptoms was estimated using a logistic regression model and a negative binomial regression model. For the latter, the outcome was reported as an incidence rate-ratio (IRR), and all models were adjusted for maternal age, educational level, parity and child age. Results: On average, and accounting for incomplete reporting, the children experienced symptoms of infection 23% of the time during one year. PFOS exposure in the high tertile compared to the low tertile was associated with a statistically significant increased proportion of days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), p-trend<0.001) and an increased odds of experiencing days with fever above the median (OR: 2.35 (95%CI: 1.31, 4.11). The latter tendency was also apparent for PFOA (OR: 1.97 (95%CI: 1.07, 3.62). Further, higher concentrations of PFOS and PFOA tended to increase the number of episodes of cooccurrence of fever and coughing and fever and nasal discharge during the one-year study period. 4 Conclusion: We found a positive association between prenatal exposure to PFOS and PFOA and the prevalence of fever, which may be a sensitive marker of infection. This finding is in agreement with an immunotoxic effect of prenatal exposure to PFAS. The wider implications for childhood infectious disease deserve attention.
Phthalates comprise a large class of chemicals used in a variety of consumer products. Several ha... more Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD); the distance from the anus to the genitals in male offspring. Few human studies have been conducted but associations between the anti-androgenic phthalates and male AGD have been reported. To study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their infants at 3 months of age (N=273). In the Odense child cohort urinary concentrations of 12 phthalate metabolites of di-ethyl, di-n-butyl-, di-iso-butyl-, di-(2-ethylhexyl)-, butyl-benzyl- and di-iso-nonyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP and DiNP, respectively) were measured among 245 mothers to boys at approximately gestational week 28 (range 20.4-30.4) and adjusted for osmolality. AGD, penile width and weight were measured 3 months after the expected...
Scandinavian journal of primary health care, Jan 20, 2015
To evaluate the effect of two intervention modalities concerning overweight and obesity among chi... more To evaluate the effect of two intervention modalities concerning overweight and obesity among children in general practice. Prospective randomized controlled trial. A total of 60 general practices in the former County of Funen, Denmark. Overweight children, identified by International Obesity Task Force criteria, aged 5-9 years. Model 1 with health consultations in general practice during a two-year period or Model 2, an educational programme for the children and their families in addition to the health consultations. Change in body mass index (BMI) z-score in order to compare the results, independent of gender- and age-related changes over time. A total of 80 children were recruited with 35 and 45 children allocated to Model 1 and Model 2, respectively. No significant differences were found in the change in BMI z-score (SDS) between the two groups. A decrease in the mean BMI z-score from baseline to study end of -0.20 (95%CI -0.38 to -0.01) in Model 1 and -0.26 (95%CI -0.44 to -0.0...
Coeliac disease (CD) affects about 1 % of the general population. Information concerning gluten i... more Coeliac disease (CD) affects about 1 % of the general population. Information concerning gluten intake in the general population is scarce. In particular, variation in gluten intake during the complementary feeding period may be an independent risk factor in CD pathogenesis. We determined the intake of gluten from wheat, barley, rye and oats in a cross-sectional National Danish Survey of Dietary Habits among Infants and Young Children (2006-2007). The study population comprised a random sample of 1743 children aged 6-36 months, recruited from the National Danish Civil Registry. The protein contents from wheat, rye, barley and oats were found in the National Danish Food Composition Table, and multiplied with the amounts in the recipes. The amounts of gluten were calculated as the amount of cereal protein × 0•80 for wheat and oats, ×0•65 for rye and ×0•50 for barley. Dietary intake was recorded daily for seven consecutive days in pre-coded food records supplemented with open-answer possibilities. Gluten intake increased with age (P < 0•0001). Oats were introduced first, rapidly outpaced by wheat, the intake of which continued to increase with age, whereas oats started to decrease at 12 months. Boys had a higher intake of energy (P ≤ 0•0001) and all types of gluten, except for barley (P ≤ 0•87). In 8-10-month-old (P < 0•0001) and 10-12-month-old (P = 0•007), but not in 6-8-month-old infants (P = 0•331), non-breast-fed infants had higher total gluten intake than partially breast-fed infants. In conclusion, this study presents representative population-based data on gluten intake in Danish infants and young children.
Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in hu... more Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in humans. They are found in consumer products, including food wrapping, cosmetics and building materials. The foetus is particularly vulnerable and exposure to these chemicals therefore is of concern for pregnant women. We investigated current exposure to several commonly used phthalates, parabens and phenols in healthy, pregnant Danish women. A total of 200 spot urine samples were collected between 8 and 30 weeks of gestation and analysed for metabolites of ten phenols, seven parabens and 16 phthalate by liquid chromatography–tandem mass spectrometry representing 26 non-persistent compounds. The majority of analytes were present in the urine sample collected from most women who participated. Thus, in 174 of the 200 women, metabolites of more than 13 (>50%) of 26 compounds were detected simultaneously. The number of compounds detected per woman (either as the parent compound or its metabo...
Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal stu... more Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA), triclosan (TCS), and parabens because of their anti-androgenic and/or estrogenic effects. Phthalates are plasticizers used in numerous industrial products. Bisphenol A is the main component of polycarbonate plastics and epoxy resins. Parabens and TCS are antimicrobial preservatives and other phenols such as benzophenone-3 (BP-3) act as a UV-screener, while chlorophenols and phenyl phenols are used as pesticides and fungicides in agriculture. In spite of the widespread use of industrial chemicals, knowledge of exposure sources and human biomonitoring studies among different segments of the population is very limited. In Denmark, we have no survey programs for non-persistent environmental chem...
Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune syst... more Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system and takes part in the surfactant homeostasis by regulating the surfactant pool size. The aims of this study were to investigate the values of SP-D in umbilical cord blood and capillary blood of premature infants and to relate the levels to perinatal conditions. A total of 254 premature infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at regular intervals throughout the admission. The concentration of SP-D in umbilical cord blood and capillary blood was measured using ELISA technique. The median concentration of SP-D in umbilical cord blood was twice as high as in mature infants, 769 ng/mL (range 140-2,551), with lowest values in infants with intrauterine growth retardation (IUGR) and rupture of membranes (ROM). The median concentration of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant treatment and susceptibility to infections. We conclude that SP-D concentrations in umbilical cord blood and capillary blood in premature infants are twice as high as in mature infants and depend on several perinatal conditions. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be related to increased risk of RDS and infections.
Based on the observation that children with a history of atopic disease show significantly increa... more Based on the observation that children with a history of atopic disease show significantly increased levels of cleaved secretory IgA in nasopharyngeal secretions, wc have previously formulated the hypothesis that bacteria-induced local deficiencies of the immune barrier of the upper respiratory tract may be a contributing factor in the development and perpetuation of atopic diseases. To evaluate this hypothesis, 25 infants were subjected to clinical, bacteriologic, and immunologic examination at the age of 18 mo, 30 mo, and 5 y. The 11 infants, who showed clinical and immunologic evidence of atopic disease at the age of 18 mo, harbored significantly higher proportions of IgAl protease-producing bacteria (median, 36%; range, 14-64%) than the 14 healthy infants (median, 5%; range. 0.4-14%). No statistically significant differences were observed at the two subsequent examinations, but healthy children showed a statistically significant increase in proportions of IgAl protease-producing bacteria in the pharynx with increasing age. IgAl protease
Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune syst... more Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system. The role of SP-D in the metabolism of surfactant is as yet quite unclear. The aims of this study were to establish normal values of SP-D in the umbilical cord blood and capillary blood of mature newborn infants and to assess the influence of perinatal conditions on these levels. A total of 458 infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at age 4 to 10 d. The concentration of SP-D in umbilical cord blood and capillary blood was measured by enzyme-linked immunosorbent assay. The median concentration of SP-D in umbilical cord blood was 392.1 ng/mL and was found to be influenced by maternal smoking and labor. The median concentration of SP-D in capillary blood was 777.5 ng/mL and was found to be influenced by the mode of delivery, the highest levels being observed in infants born by cesarean section. It was concluded that SP-D concentrations in umbilical cord blood and capillary blood are highly variable and depend on several perinatal conditions. Further studies are needed to elucidate the effect of respiratory distress and infection on SP-D concentrations.
Bovine colostrum, the first milk that cows produce after parturition, contains high levels of gro... more Bovine colostrum, the first milk that cows produce after parturition, contains high levels of growth factors and immunomodulatory components. Some healthy and diseased individuals may gain health benefits by consuming bovine colostrum as a food supplement. This review provides a systematic, critical evaluation of the current state of knowledge in this area. Fifty-one eligible studies were identified from the following databases: Medline, Embase, Global Health, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature. Studies were heterogeneous with regard to populations, outcomes, and methodological quality, as judged by the Jadad assessment tool. Many studies used surrogate markers to study the effects of bovine colostrum. Studies suggesting clinical benefits of colostrum supplementation were generally of poor methodological quality, and results could not be confirmed by other investigators. Bovine colostrum may provide gastrointestinal and immunological benefits, but further studies are required before recommendations can be made for clinical application. Animal models may help researchers to better understand the mechanisms of bovine colostrum supplementation, the dosage regimens required to obtain clinical benefits, and the optimal methods for testing these effects in humans.
F1000 - Post-publication peer review of the biomedical literature, 2013
Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac... more Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an illdefined component of innate immunity in celiac disease. We identify the -amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4-MD2-CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients' biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.
Background: An association between cow's milk hypersensitivity (CMH) and gastro-oesophageal reflu... more Background: An association between cow's milk hypersensitivity (CMH) and gastro-oesophageal reflux disease (GERD) in childhood has been reported in the past decade. Aim: To assess whether biopsies from the upper gastrointestinal tract of children with cow's milk sensitive GERD have a specific allergic inflammatory pattern, and to compare two different techniques for measuring inflammatory cells in gastrointestinal biopsies. Methods: GERD was diagnosed by means of endoscopy and oesophageal pH monitoring. Hypersensitivity to cow's milk was determined by an elimination diet and cow's milk challenge. Allergic inflammatory cells in upper gastrointestinal biopsies were identified by immunohistochemistry and their numbers were assessed by two different methods-counting the number of cells/high power field and using the computerised Cast-Grid system. Results: Cow's milk sensitive GERD was identified in 10 of 17 children with severe GERD (median age, 7.8 years). Biopsies from children with endoscopic oesophagitis had significantly increased numbers of mast cells and T cells. No differences in the number of eosinophils, mast cells, or T cells were found between children with CMH and those with primary GERD. Several differences were found between the two different histological quantification methods. Conclusions: CMH was found not only in infants but also in school age children with GERD. Histology did not identify the cow's milk sensitive GERD subgroup. The computerised histological method provides a more complete evaluation based upon total biopsy area, and helped to limit the bias of uneven biopsy size.
This thesis is based on 9 papers on the uptake of dietary antigens and on the humoral immune resp... more This thesis is based on 9 papers on the uptake of dietary antigens and on the humoral immune responses to dietary antigens, in healthy subjects and in patients with coeliac disease or atopic eczema. Work in experimental animals have indicated that dietary antigens are taken up in amounts, which are nutritionally insignificant, but may be of immunological importance. Local or systemic antibodies may retard the uptake, but in addition may increase the uptake of unrelated antigens. In humans the uptake of intact dietary antigen, free or in immune complexes, was reported in studies in healthy subjects and in patients with immune deficiency or atopy. We investigated the uptake of dietary antigen in 8 healthy subjects after a test meal, using ELISA methods and high performance liquid chromatography (HPLC) for the fractionation of serum samples. A significant finding was that ovalbumin (OA) was taken up as intact antigen or as a high MW immune complex constituent in all the 8 subjects. IgG...
Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians... more Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, HLA genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/ undetectable,anIgG-basedtest is indicated.Patientswithpositiveresultsshould...
Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive de... more Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive development in early childhood and increased incidence of infections; however, the longitudinal association between early-life factors and ID in 18-month-old children in Denmark is unknown. The present study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort. The questionnaires were modified from those used in the Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of seventy-nine children due to chronic disease, acute infection, C-reactive protein >10 mg/l, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for ...
Introduction Many aspects of the management of esophageal atresia (EA) and tracheoesophageal fist... more Introduction Many aspects of the management of esophageal atresia (EA) and tracheoesophageal fistula (TEF) are controversial and the evidence for decision making is limited. Members of the European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) conducted a consensus conference on the surgical management of EA/TEF based on expert opinions referring to the latest literature. Materials and Methods Nineteen ERNICA representatives from nine European countries participated in the conference. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing the domains diagnostics, preoperative, operative, and postoperative management, and literature review. The 2-day conference was held in Berlin in October 2018. Anonymous voting was conducted via an internet-based system. Consensus was defined when 75% of the votes scored 6 to 9. Results Fifty-two items were generated with 116 relevant articles of which five s...
Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into ad... more Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into adulthood, and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in breast milk have been suggested as mediators of the beneficial long-term effect of breastfeeding on BP and BLP. We aimed to investigate associations between n-3 LC-PUFA content in breast milk at 4 months postpartum and offspring BP and BLP in early life. BP and BLP were measured at 4, 18, and 36 months. Statistical analyses were sex-stratified and adjusted for gestational age, maternal pre-pregnancy body mass index (BMI), and maternal educational level. Based on 336 mother-child dyads, high n-3 LC-PUFA in breast milk was inversely associated with systolic and diastolic BP in boys at 4 months (β = −20.0 (95% CI = −33.4, −6.7), p = 0.004 and β = −10.2 (95% CI = −19.8, −0.5), p = 0.039, respectively); inversely associated with HDL cholesterol, and directly associated with triglyceride in girls at 4 months (β = −0.7 (95% C...
Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoyleth... more Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA), which induce satiety through endogenous formation in the small intestine upon feeding, but also when orally or systemic administered. OEA, SEA, and PEA are present in human milk, and we hypothesized that the content of OEA, SEA, and PEA in mother’s milk differed for infants being heavy (high weight-for-age Z-score (WAZ)) or light (low WAZ) at time of milk sample collection. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of OEA, SEA, and PEA in milk samples collected four months postpartum from mothers to high (n = 50) or low (n = 50) WAZ infants. Associations between OEA, SEA, and PEA concentration and infant anthropometry at four months of age as well as growth from birth were investigated using linear and logistic regression analyses, adjusted for birth ...
Introduction: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that... more Introduction: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that have resulted in global environmental exposures. Previous epidemiological studies have reported possible effects on the immune system after developmental PFAS exposure, but the possible impact on childhood infectious disease is unclear. Objectives: To investigate the association between prenatal exposure to PFAS and symptoms of infections at age 1-4 years. Methods: The Odense Child Cohort is an ongoing prospective study on children's health, where serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in 649 pregnant women before gestational week 16. Of these women, 359 reported on symptoms of infection in their child every two weeks for a one-year period. The association between prenatal exposure to PFAS and the symptoms was estimated using a logistic regression model and a negative binomial regression model. For the latter, the outcome was reported as an incidence rate-ratio (IRR), and all models were adjusted for maternal age, educational level, parity and child age. Results: On average, and accounting for incomplete reporting, the children experienced symptoms of infection 23% of the time during one year. PFOS exposure in the high tertile compared to the low tertile was associated with a statistically significant increased proportion of days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), p-trend<0.001) and an increased odds of experiencing days with fever above the median (OR: 2.35 (95%CI: 1.31, 4.11). The latter tendency was also apparent for PFOA (OR: 1.97 (95%CI: 1.07, 3.62). Further, higher concentrations of PFOS and PFOA tended to increase the number of episodes of cooccurrence of fever and coughing and fever and nasal discharge during the one-year study period. 4 Conclusion: We found a positive association between prenatal exposure to PFOS and PFOA and the prevalence of fever, which may be a sensitive marker of infection. This finding is in agreement with an immunotoxic effect of prenatal exposure to PFAS. The wider implications for childhood infectious disease deserve attention.
Phthalates comprise a large class of chemicals used in a variety of consumer products. Several ha... more Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD); the distance from the anus to the genitals in male offspring. Few human studies have been conducted but associations between the anti-androgenic phthalates and male AGD have been reported. To study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their infants at 3 months of age (N=273). In the Odense child cohort urinary concentrations of 12 phthalate metabolites of di-ethyl, di-n-butyl-, di-iso-butyl-, di-(2-ethylhexyl)-, butyl-benzyl- and di-iso-nonyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP and DiNP, respectively) were measured among 245 mothers to boys at approximately gestational week 28 (range 20.4-30.4) and adjusted for osmolality. AGD, penile width and weight were measured 3 months after the expected...
Scandinavian journal of primary health care, Jan 20, 2015
To evaluate the effect of two intervention modalities concerning overweight and obesity among chi... more To evaluate the effect of two intervention modalities concerning overweight and obesity among children in general practice. Prospective randomized controlled trial. A total of 60 general practices in the former County of Funen, Denmark. Overweight children, identified by International Obesity Task Force criteria, aged 5-9 years. Model 1 with health consultations in general practice during a two-year period or Model 2, an educational programme for the children and their families in addition to the health consultations. Change in body mass index (BMI) z-score in order to compare the results, independent of gender- and age-related changes over time. A total of 80 children were recruited with 35 and 45 children allocated to Model 1 and Model 2, respectively. No significant differences were found in the change in BMI z-score (SDS) between the two groups. A decrease in the mean BMI z-score from baseline to study end of -0.20 (95%CI -0.38 to -0.01) in Model 1 and -0.26 (95%CI -0.44 to -0.0...
Coeliac disease (CD) affects about 1 % of the general population. Information concerning gluten i... more Coeliac disease (CD) affects about 1 % of the general population. Information concerning gluten intake in the general population is scarce. In particular, variation in gluten intake during the complementary feeding period may be an independent risk factor in CD pathogenesis. We determined the intake of gluten from wheat, barley, rye and oats in a cross-sectional National Danish Survey of Dietary Habits among Infants and Young Children (2006-2007). The study population comprised a random sample of 1743 children aged 6-36 months, recruited from the National Danish Civil Registry. The protein contents from wheat, rye, barley and oats were found in the National Danish Food Composition Table, and multiplied with the amounts in the recipes. The amounts of gluten were calculated as the amount of cereal protein × 0•80 for wheat and oats, ×0•65 for rye and ×0•50 for barley. Dietary intake was recorded daily for seven consecutive days in pre-coded food records supplemented with open-answer possibilities. Gluten intake increased with age (P < 0•0001). Oats were introduced first, rapidly outpaced by wheat, the intake of which continued to increase with age, whereas oats started to decrease at 12 months. Boys had a higher intake of energy (P ≤ 0•0001) and all types of gluten, except for barley (P ≤ 0•87). In 8-10-month-old (P < 0•0001) and 10-12-month-old (P = 0•007), but not in 6-8-month-old infants (P = 0•331), non-breast-fed infants had higher total gluten intake than partially breast-fed infants. In conclusion, this study presents representative population-based data on gluten intake in Danish infants and young children.
Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in hu... more Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in humans. They are found in consumer products, including food wrapping, cosmetics and building materials. The foetus is particularly vulnerable and exposure to these chemicals therefore is of concern for pregnant women. We investigated current exposure to several commonly used phthalates, parabens and phenols in healthy, pregnant Danish women. A total of 200 spot urine samples were collected between 8 and 30 weeks of gestation and analysed for metabolites of ten phenols, seven parabens and 16 phthalate by liquid chromatography–tandem mass spectrometry representing 26 non-persistent compounds. The majority of analytes were present in the urine sample collected from most women who participated. Thus, in 174 of the 200 women, metabolites of more than 13 (>50%) of 26 compounds were detected simultaneously. The number of compounds detected per woman (either as the parent compound or its metabo...
Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal stu... more Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA), triclosan (TCS), and parabens because of their anti-androgenic and/or estrogenic effects. Phthalates are plasticizers used in numerous industrial products. Bisphenol A is the main component of polycarbonate plastics and epoxy resins. Parabens and TCS are antimicrobial preservatives and other phenols such as benzophenone-3 (BP-3) act as a UV-screener, while chlorophenols and phenyl phenols are used as pesticides and fungicides in agriculture. In spite of the widespread use of industrial chemicals, knowledge of exposure sources and human biomonitoring studies among different segments of the population is very limited. In Denmark, we have no survey programs for non-persistent environmental chem...
Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune syst... more Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system and takes part in the surfactant homeostasis by regulating the surfactant pool size. The aims of this study were to investigate the values of SP-D in umbilical cord blood and capillary blood of premature infants and to relate the levels to perinatal conditions. A total of 254 premature infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at regular intervals throughout the admission. The concentration of SP-D in umbilical cord blood and capillary blood was measured using ELISA technique. The median concentration of SP-D in umbilical cord blood was twice as high as in mature infants, 769 ng/mL (range 140-2,551), with lowest values in infants with intrauterine growth retardation (IUGR) and rupture of membranes (ROM). The median concentration of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant treatment and susceptibility to infections. We conclude that SP-D concentrations in umbilical cord blood and capillary blood in premature infants are twice as high as in mature infants and depend on several perinatal conditions. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be related to increased risk of RDS and infections.
Based on the observation that children with a history of atopic disease show significantly increa... more Based on the observation that children with a history of atopic disease show significantly increased levels of cleaved secretory IgA in nasopharyngeal secretions, wc have previously formulated the hypothesis that bacteria-induced local deficiencies of the immune barrier of the upper respiratory tract may be a contributing factor in the development and perpetuation of atopic diseases. To evaluate this hypothesis, 25 infants were subjected to clinical, bacteriologic, and immunologic examination at the age of 18 mo, 30 mo, and 5 y. The 11 infants, who showed clinical and immunologic evidence of atopic disease at the age of 18 mo, harbored significantly higher proportions of IgAl protease-producing bacteria (median, 36%; range, 14-64%) than the 14 healthy infants (median, 5%; range. 0.4-14%). No statistically significant differences were observed at the two subsequent examinations, but healthy children showed a statistically significant increase in proportions of IgAl protease-producing bacteria in the pharynx with increasing age. IgAl protease
Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune syst... more Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system. The role of SP-D in the metabolism of surfactant is as yet quite unclear. The aims of this study were to establish normal values of SP-D in the umbilical cord blood and capillary blood of mature newborn infants and to assess the influence of perinatal conditions on these levels. A total of 458 infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at age 4 to 10 d. The concentration of SP-D in umbilical cord blood and capillary blood was measured by enzyme-linked immunosorbent assay. The median concentration of SP-D in umbilical cord blood was 392.1 ng/mL and was found to be influenced by maternal smoking and labor. The median concentration of SP-D in capillary blood was 777.5 ng/mL and was found to be influenced by the mode of delivery, the highest levels being observed in infants born by cesarean section. It was concluded that SP-D concentrations in umbilical cord blood and capillary blood are highly variable and depend on several perinatal conditions. Further studies are needed to elucidate the effect of respiratory distress and infection on SP-D concentrations.
Bovine colostrum, the first milk that cows produce after parturition, contains high levels of gro... more Bovine colostrum, the first milk that cows produce after parturition, contains high levels of growth factors and immunomodulatory components. Some healthy and diseased individuals may gain health benefits by consuming bovine colostrum as a food supplement. This review provides a systematic, critical evaluation of the current state of knowledge in this area. Fifty-one eligible studies were identified from the following databases: Medline, Embase, Global Health, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature. Studies were heterogeneous with regard to populations, outcomes, and methodological quality, as judged by the Jadad assessment tool. Many studies used surrogate markers to study the effects of bovine colostrum. Studies suggesting clinical benefits of colostrum supplementation were generally of poor methodological quality, and results could not be confirmed by other investigators. Bovine colostrum may provide gastrointestinal and immunological benefits, but further studies are required before recommendations can be made for clinical application. Animal models may help researchers to better understand the mechanisms of bovine colostrum supplementation, the dosage regimens required to obtain clinical benefits, and the optimal methods for testing these effects in humans.
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Papers by Steffen Husby