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Comparing Paternal and Maternal Factors in Childhood Atopic Dermatitis
Abstract
Atopic dermatitis (AD) is a common inflammatory skin disease that chronically affects children and adults worldwide. Environmental exposures, heritable factors, immune dysregulation, and skin barrier malfunction all contribute to the multifactorial nature of AD. It is known that maternal and paternal influences are important predictors for the risk of AD in offspring. This review examines and compares the evidence and mechanisms behind specific maternal and paternal factors that may contribute to the pathogenesis of AD.
... A history of atopic disease in the immediate family appears to be more highly correlated with a diagnosis of AD than a history in any family member, 86 and the significance of family history to the development of atopic disease appears to decrease with the age of patients with AD. 54 However, the majority of studies have found a high frequency of parents with allergy among patients with a confirmed AD diagnosis. 87 Family history is also a strong predictor for persistence of other atopic conditions such as asthma. 56,88,89 In the Pollution and Asthma Risk: an Infant Study (PARIS) cohort, parental history of asthma and/or allergic rhinitis and/or eczema was associated with a severe atopic phenotype. ...
... 78 Parental history has been shown to have sex-specific effects on the risk of allergy and asthma. 87,90,91 Atopic dermatitis severity There is general agreement among clinicians that patients with more severe AD tend to present with multimorbidity and more persistent disease. Unfortunately, most birth cohort studies do not include measures of disease severity or have insufficient patients with severe disease; therefore, the rate of persistence may be diluted by the inclusion of patients with mild disease. ...
Eczema (also known as atopic dermatitis or AD) is a complex skin condition that generally develops in early childhood, affecting 15 to 20% of children worldwide. Although it clears by itself in some children, it persists into adulthood in many children, contrary to popular belief. Many children develop related allergic diseases such as asthma, allergic rhinitis and eosinophilic oesophagitis (allergic inflammation of the oesophagus), a pathway known as the “atopic march”. The authors, based in Ireland and the U.S.A., aimed to find reproducible patterns (i.e. clinically relevant characteristics) that could help doctors predict whether childhood AD will clear or progress, by surveying several recent studies with large patient cohorts (groups studied). These studies show that most atopic children, in fact, do not follow the classical “atopic march” but can follow various disease courses. Although the data came from different sources or were described in different ways, the authors identified common characteristics of early‐childhood AD that may help estimate risk of developing persistent disease (i.e. that progresses into adulthood) and related allergic diseases. They found that children who get severe AD at a very young age and who have parents with a history of related diseases, have a higher risk of disease progression. Genetic factors, allergies, and living in an urban environment also increase this risk. The authors provide a practitioner's guide that could help doctors to identify children with AD at higher risk of disease progression and to decide on the best course of action for their treatment, such as regular check‐ups or referring them to a specialist for further testing or treatment. Linked Article: Irvine and Mina‐Osorio Br J Dermatol 2019; 181:895–906
... 12,13 These findings provide a rationale for early life skin-directed treatment to enhance the barrier function and possibly prevent AD. [14][15][16] The most prominent risk factors for the development of AD are parental allergic disease and the presence of mutations in the gene encoding filaggrin (FLG). 1,6,17 The most consistent environmental risk factors are low UV-light exposure, dry climate, urban living, small family size, high parental education level, and repeated treatment with antibiotics in early childhood. 17,18 In addition, the association between caesarean section and offspring allergic disease has been extensively investigated, however with conflicting results. ...
... 1,6,17 The most consistent environmental risk factors are low UV-light exposure, dry climate, urban living, small family size, high parental education level, and repeated treatment with antibiotics in early childhood. 17,18 In addition, the association between caesarean section and offspring allergic disease has been extensively investigated, however with conflicting results. [19][20][21] Increased knowledge of predictive factors of skin barrier dysfunction and AD in infancy is warranted to provide targeted prevention strategies. ...
Background:
Dry skin, associated with increased transepidermal water loss (TEWL), is found to precede atopic dermatitis (AD) in childhood.
Objective:
We aimed to identify parental, prenatal and perinatal predictive factors of dry skin, high TEWL and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months.
Methods:
From the Preventing Atopic Dermatitis and Allergies in children (PreventADALL) prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL and eczema were assessed at 3- and 6 months investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL > 90th percentile, equalling 11.3 g/m2/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts.
Results:
Significant predictive factors (p<0.05) for dry skin at 3 months were delivery > 38 gestational weeks and paternal age > 37 years, for high TEWL; male sex, birth during winter season and maternal allergic disease, and for eczema; elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months, (ORadjusted: 1.92, 95% CI: 1.21-3.05, p=0.005), while high TEWL at 3 months was not.
Conclusion:
In early infancy, distinct parental and pregnancy-related factors were predictive for dry skin, high TEWL and AD. Dry skin at 3 months of age was predictive for AD three months later.
... 54 However, the majority of studies have found a high frequency of parents with allergy among patients with a confirmed AD diagnosis. 87 Family history is also a strong predictor for persistence of other atopic conditions such as asthma. 88,89,56 In the Pollution and Asthma Risk: an Infant Study (PARIS) cohort, parental history of asthma and/or allergic rhinitis and/or eczema was associated with a severe atopic phenotype. ...
... 78 Parental history has been shown to have gender-specific effects on the risk of allergy and asthma. 87,90,91 AD severity There is a general agreement among clinicians that patients with more severe AD tend to present with multimorbidity and more persistent disease. Unfortunately, most birth cohort studies do not include measures of disease severity or have insufficient patients with severe disease; therefore, the rate of persistence may be diluted by the inclusion of patients with mild disease. ...
Background
Atopic dermatitis (AD) is a heterogeneous disease with a multifactorial aetiology and complex pathophysiology. This heterogeneity translates into different trajectories of disease progression with respect to severity, persistence, and risk of development of atopic comorbidities. Determining which possible disease trajectories or comorbidities any individual child might develop is challenging in clinical practice. Tools that help identify paediatric patients at higher risk of disease progression would greatly aid clinicians.
Methods
We reviewed recent cohort studies to synthesise and simplify the epidemiological data to try to identify shared clinically relevant characteristics that may help physicians estimate the risk of disease progression in paediatric patients with AD.
Results
Despite the variability in data collection and methods of analysis and their limitations, there are common patterns of early‐childhood AD which may aid in the estimation of risk for disease progression. Factors associated with risk of AD progression include younger age of onset, family history of atopy, greater AD severity, filaggrin mutations, urban environment and polysensitisation and/or allergic multimorbidity. Based on these factors, we provide a practitioner's guide for identifying, counselling and/or referring infants/children with AD at potentially higher risk of developing persistent AD and atopic comorbidities and clinical scenarios to illustrate how these data relate to real‐life situations.
Conclusions
Useful insights are provided for physicians and patients to better inform about risk of AD progression and to help guide care pathways for the AD paediatric population.
This article is protected by copyright. All rights reserved.
... Вероятно, это обусловлено тем, что группа обследуемых с отягощенным анамнезом по аллергическим заболеваниям была неоднородна, включала детей с отягощенным анамнезом по материнской, отцовской линии и/или со стороны сиблинга. В этом контексте следует отметить, что в литературе продолжает обсуждаться факт разного влияния материнской и отцовской наследственности на риск манифестации аллергического заболевания у ребенка, данные часто противоречивы, зависят от вида аллергического заболевания у отца и матери, пола ребенка [16,17]. Относительно небольшое количество детей в группах в рамках пилотного исследования не позволило провести анализ распределения частот генотипов изучаемых полиморфизмов у детей в зависимости от того, отягощен аллергоанамнез у них по материнской, отцовской линии и/или со стороны сиблинга. ...
Background. Cytokine and toll-like receptor gene polymorphisms may impact oral tolerance formation in infants. Objective: To determine the genotype distribution of IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms in children with different family history of allergy residing in Grodno region; to analyze the association between gene polymorphisms and concentrations of fecal calprotectin (FCP) and urine eosinophil protein X (UEoPX) in infants. Material and Methods. 92 infants were recruited and analyzed for IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms. Concentrations of FCP and UEoPX were examined in dynamics in children aged 1 and 3 months. Results. 80.4% and 48.9% of infants were carriers of the mutant allele of the G1082A and C592A polymorphisms respectively. 70.5% of children with negative family history of allergy were carriers of the wild G allele of G1082A polymorphism. Carriage of the mutant A allele of G1082A polymorphism is associated with lower FCP concentration in infants aged 1 month (AA: 1.9 ng/mL [1.9; 3.1], GA: 15.9 ng/mL [1.9; 93.8]) and GG: 88.3 ng/mL [2.4; 230.1]). The level of UEoPX in 3 months old infants with homozygote AA genotype was significantly (p=0.019) higher than in infants with heterozygote CA genotype (3.2 ng/ml [2.4; 4.5] and 2.3 ng/ml [1.3; 3.3] respectively). Conclusion. Carriage of the wild G allele of G1082A polymorphism is associated with higher fecal calprotectin concentration in one month old infants and significantly lower level of urine eosinophil protein X in 3 months old infants.
... Previous studies have proved that more mothers of children with AD had received therapy for autoimmune diseases compared to mothers of normal children [6]. However, both maternal and paternal autoimmune diseases may be associated with the occurrence of allergic diseases in their children [6][7][8]. ...
Atopic dermatitis (AD) is a common inflammatory skin disorder induced by dysfunction of immune suppression sharing similar pathogenesis to autoimmune diseases. To explore the association between autoimmune diseases and AD in children, we linked the birth data from National Birth Registry with National Health Insurance Research Database. There were 1,174,941 children obtained from 2006 to 2012 birth cohort. A total of 312,329 children diagnosed with AD before 5 years old were compared to 862,612 children without AD in the control group. Conditional logistic regression was utilized to calculate adjusted odds ratio (OR) and Bonferroni-corrected confidence interval (CI) for overall significance level of 0.05. In 2006–2012 birth cohort, the prevalence rate of AD was 26.6% (95% CI 26.5, 26.7) before 5 years of age. Having parental autoimmune disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, ankylosing spondylitis, and psoriasis) was associated with a significant higher risk of children AD development. The other associated factors were maternal obstetric complications (including gestational diabetes mellitus and cervical incompetence), parental systemic diseases (including anemia, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, hyperthyroidism, and obstructive sleep apnea), and parental allergic disease (including asthma and AD). The subgroup analysis showed similar results between children’s sexes. Moreover, maternal autoimmune disease had higher impact on the risk of developing AD in the child compared with paternal autoimmune disease. In conclusion, parental autoimmune diseases were found to be related to their children’s AD before 5 years old.
... 6 On the other hands, both maternal and paternal autoimmune diseases may give rise to the occurrence of allergic diseases in their children. [6][7][8] Genes play an important role in linking AD and autoimmune diseases. The commonality of these two diseases based on the dysfunction of immune suppression, and the mechanism of which could be interpreted by the overlapping genetic loci, molecular pathway and disease-implicated cell type. ...
Atopic dermatitis(AD) is a common inflammatory skin disorder induced by dysfunction of immune suppression, which resembles the mechanism of autoimmune diseases. To explore the association between autoimmune diseases and AD in their children, we linked the birth data from National Birth Registry with National Health Insurance Research Database. Demographic characteristics from 1174,941 parent-child linkages were obtained. There were 312,329 children diagnosed with AD before 5 years old, and they would be compared with the other 862,612 children without AD in the control group. Conditional logistic regression was utilized to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). After adjusting infant’s characteristics, perinatal factors, and other parental diseases, the odds ratio of parental rheumatoid arthritis(RA) was 2.269 (95% CI 1.333–3.861) and parental psoriasis was1.610 (95% CI, 1.094–2.369). Parental allergic diseases such as AD (aOR 2.071, 95% CI 1.952–2.198) and asthma (aOR 1.494, 95% CI 1.400-1.594) were also significant predictors for childhood AD. The subgroup analysis showed significant difference between children’s sex. Parental RA (aOR 3.070, 95% CI, 1.532–6.154) was crucial for boys, while parental psoriasis (aOR 1.945, 95% CI, 1.129–3.350)was a risk factor for girls.
In conclusion, parental autoimmune diseases were found to be related to AD in their children before 5 years old. Additionally, there were different risk factors for AD between children’s sex.
... Variable rates of AD across the included studies, ranging from 1.0% to 43.5%, might reflect differences in environmental exposures or genetic susceptibility. 50 Despite this variability in AD rates across the 30 studies included in these meta-analyses, the relationships between BW and the adjusted OR for AD were remarkably consistent within each meta-analysis of this outcome in children and infants. This is particularly interesting given the report from the ISAAC phase III studies that low BW, defined as BW of less than 2.5 kg and unadjusted for gestational age, was associated with lower risks of AD within affluent countries but not in nonaffluent countries. ...
Background:
Individual susceptibility to allergic diseases is developmentally programmed by early-life exposures. Evidence from preclinical studies suggests that intrauterine growth restriction is protective against later inflammatory responses to allergens.
Objective:
We sought to evaluate whether prenatal growth affects susceptibility to allergy in human subjects.
Methods:
We systematically searched for relevant studies in 11 databases, including Web of Science, ProQuest, EMBASE, and PubMed. We included only studies that corrected for gestational age or were restricted to full-term infants to separate effects of fetal growth from those of prematurity.
Results:
The 42 eligible studies included prospective and retrospective cohort, cross-sectional, and case-control studies. Only 2 studies reported allergic asthma. A birth weight increase of 1 kg was associated with a 44% greater risk of food allergy in children (odds ratio [OR], 1.44; 95% CI, 1.04-1.99; P = .001), a 17% greater risk of ever allergic dermatitis in children (OR, 1.17; 95% CI, 1.04-1.32; P = .008), and a 34% greater risk of ever or current allergic dermatitis in infants up to 2 years of age (OR, 1.34; 95% CI, 1.08-1.68; P = .009). Risks of allergic rhinitis were not associated with birth weight.
Conclusions:
The results of these meta-analyses suggest that intrauterine growth restriction protects against allergic diseases in human subjects consistent with preclinical evidence but that effects might differ between allergic diseases. The strongest evidence is available for infancy and early childhood, and additional studies in older children and adults are needed to determine whether the effects of prenatal growth on each allergic disease persist or differ between those with severe and mild phenotypes.
Background:
Factors predicting allergic sensitization in the first 6 months of life are poorly understood. We aimed to determine whether eczema, dry skin, and high transepidermal water loss (TEWL) at 3 months were associated with allergic sensitization at 6 months of age and, secondarily, to establish whether these characteristics predicted sensitization from 3 to 6 months of age.
Methods:
At 3 months of age, 1,994 infants from the population-based PreventADALL birth cohort in Norway and Sweden were assessed for eczema and dry skin on the cheeks and/or extensors; impaired skin barrier function, defined as TEWL in the upper quartile (>9.4 g/m2 /h), and allergen-specific IgE-levels <0.1 kUA /L, available in 830. At 6 months, we assessed allergic sensitization to any food (egg, cow's milk, peanut, wheat, soy) or inhalant (birch, timothy grass, dog, cat) allergen by a skin prick test wheal diameter ≥2 mm larger than negative control.
Results:
Any sensitization was found in 198 of the 1,994 infants (9.9%), the majority to food allergens (n=177, 8.9%). Eczema, dry skin, and high TEWL at 3 months increased the risk of sensitization at 6 months; adjusted odds ratios 4.20 (95% CI 2.93-6.04), 2.09 (95% CI 1.51-2.90) and 3.67 (95% CI 2.58-5.22), respectively. Eczema predicted sensitization with 55.6% sensitivity and 68.1% specificity; dry skin with 65.3% sensitivity and 57.3% specificity; and high TEWL with 61.7% sensitivity and 78.1% specificity.
Conclusion:
Eczema, dry skin, and high TEWL at 3 months predicted allergic sensitization at 6 months of age.
Background
Although in all sexually reproducing organisms an individual has a mother and a father, non-genetic inheritance has been predominantly studied in mothers. Paternal effects have been far less frequently studied, until recently. In the last 5 years, research on environmentally induced paternal effects has grown rapidly in the number of publications and diversity of topics. Here, we provide an overview of this field using synthesis of evidence (systematic map) and influence (bibliometric analyses).
Results
We find that motivations for studies into paternal effects are diverse. For example, from the ecological and evolutionary perspective, paternal effects are of interest as facilitators of response to environmental change and mediators of extended heredity. Medical researchers track how paternal pre-fertilization exposures to factors, such as diet or trauma, influence offspring health. Toxicologists look at the effects of toxins. We compare how these three research guilds design experiments in relation to objects of their studies: fathers, mothers and offspring. We highlight examples of research gaps, which, in turn, lead to future avenues of research.
Conclusions
The literature on paternal effects is large and disparate. Our study helps in fostering connections between areas of knowledge that develop in parallel, but which could benefit from the lateral transfer of concepts and methods.
Importance:
Pruritus, a hallmark of atopic dermatitis (AD), is thought to disrupt sleep, yet little is known about how variations in disease activity and severity of this common childhood condition may be associated with sleep patterns over time.
Objective:
To determine whether children with active AD have impaired sleep duration and quality at multiple time points throughout childhood and whether disease severity affects sleep outcomes.
Design, setting, and participants:
This longitudinal cohort study used data of children enrolled in the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in Avon, United Kingdom. Participants were children (N = 13 988) alive at 1 year and followed up with repeated measures of self-reported AD and sleep through 16 years of age. This study was based on data collected from 1990 to 2008. Data analysis was performed from September 2017 to September 2018.
Main outcomes and measures:
Standardized measure of sleep duration and composite measure of sleep quality, including nighttime awakenings, early morning awakenings, difficulty falling asleep, and nightmares, were repeated at multiple time points between 2 and 16 years of age.
Results:
The study sample comprised 13 988 children (7220 male [51.6%]) followed up for a median (interquartile range [IQR]) duration of 11 (5-14) years. Of this total, 4938 children (35.3%) met the definition of having atopic dermatitis between 2 and 16 years of age. Total sleep duration was similar between children with active AD and without AD at all ages, and the average estimated difference across childhood was a clinically negligible difference of 2 minutes less per day for children with AD (95% CI, -4 to 0 minutes). In contrast, children with active AD were more likely to report worse sleep quality at all time points, with a nearly 50% higher odds of experiencing more sleep-quality disturbances (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33 to 1.66). Children with more severe active disease (quite bad or very bad AD: aOR, 1.68; 95% CI, 1.42 to 1.98) and with comorbid asthma or allergic rhinitis (aOR, 1.79; 95% CI, 1.54 to 2.09) had worse sleep quality. However, even children with mild AD (OR, 1.40; 95% CI, 1.27 to 1.54) or inactive AD (OR, 1.41; 95% CI, 1.28 to 1.55) had statistically significantly increased odds of impaired sleep quality.
Conclusions and relevance:
Atopic dermatitis appeared to be associated with impaired sleep quality throughout childhood; thus, it is suggested that clinicians should consider sleep quality among all children with AD, especially those with comorbid asthma or allergic rhinitis and severe disease, and that interventions to improve sleep quality are needed.
To determine the association of socioeconomic disadvantage with the prevalence of childhood disabling chronic conditions in high-income countries.
Systematic review and meta-analyses.
6 electronic databases, relevant websites, reference lists and experts in the field.
160 observational studies conducted in high-income countries with data on socioeconomic status and disabling chronic conditions in childhood, published between 1 January 1991 and 31 December 2013.
Abstracts were reviewed, full papers obtained, and papers identified for inclusion by 2 independent reviewers. Inclusion decisions were checked by a third reviewer. Where reported, ORs were extracted for low versus high socioeconomic status. For studies reporting raw data but not ORs, ORs were calculated. Narrative analysis was undertaken for studies without data suitable for meta-analysis.
126 studies had data suitable for meta-analysis. ORs for risk estimates were: all-cause disabling chronic conditions 1.72 (95% CI 1.48 to 2.01); psychological disorders 1.88 (95% CI 1.68 to 2.10); intellectual disability 2.41 (95% CI 2.03 to 2.86); activity-limiting asthma 2.20 (95% CI 1.87 to 2.85); cerebral palsy 1.42 (95% CI 1.26 to 1.61); congenital abnormalities 1.41 (95% CI 1.24 to 1.61); epilepsy 1.38 (95% CI 1.20 to 1.59); sensory impairment 1.70 (95% CI 1.39 to 2.07). Heterogeneity was high across most estimates (I(2)>75%). Of the 34 studies without data suitable for meta-analysis, 26 reported results consistent with increased risk associated with low socioeconomic status.
The findings indicate that, in high-income countries, childhood disabling chronic conditions are associated with social disadvantage. Although evidence of an association is consistent across different countries, the review provides limited evidence to explain the association; future research, using longitudinal data, will be required to distinguish low socioeconomic status as the cause or consequence of childhood disabling chronic conditions and the aetiological pathways and mechanisms.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Background
The mechanism(s) responsible for acquisition of maternal antibody isotypes other than IgG are not fully understood. This uncertainty is a major reason underlying the continued controversy regarding whether cord blood (CB) IgE originates in the mother or fetus.Objective
To investigate the capacity of maternal IgE to be transported across the placenta in the form of IgG anti-IgE/IgE immune complexes (ICs) and to determine the role of the neonatal Fc receptor (FcRn) in mediating this process.Methods
Maternal and CB serum concentrations of IgE, IgG anti-IgE, and IgG anti-IgE/IgE ICs were determined in a cohort of allergic and non-allergic mother/infant dyads. Madin-Darby Canine Kidney (MDCK) cells stably transfected with human FcRn were used to study the binding and transcytosis of IgE in the form of IgG anti-IgE/IgE ICs.ResultsMaternal and CB serum concentrations of IgG anti-IgE/IgE ICs were highly correlated, regardless of maternal allergic status. IgG anti-IgE/IgE ICs generated in vitro bound strongly to FcRn-expressing MDCK cells and were transcytosed in an FcRn-dependent manner. Conversely, monomeric IgE did not bind to FcRn and was not transcytosed. IgE was detected in solutions of transcytosed IgG anti-IgE/IgE ICs, even though essentially all the IgE remained in complex form. Similarly, the majority of IgE in CB sera was found to be complexed to IgG.Conclusions and Clinical RelevanceThese data indicate that human FcRn facilitates the transepithelial transport of IgE in the form of IgG anti-IgE/IgE ICs. They also strongly suggest that the majority of IgE in CB sera is the result of FcRn-mediated transcytosis of maternal-derived IgG anti-IgE/IgE ICs. These findings challenge the widespread perception that maternal IgE does not cross the placenta. Measuring maternal or CB levels of IgG anti-IgE/IgE ICs may be a more accurate predictor of allergic risk.This article is protected by copyright. All rights reserved.
Atopic dermatitis is a chronic inflammatory skin disease that affects 10–20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31–33, 6p21.3, 12q15–24.1, 13q12–31, and 14q11.2/14q32.1–32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS'90), parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12–14 and 5q31–33.Keywords: genetics, marker analysis
The aim was to investigate suicide and "undetermined" deaths by age, economic activity status, and social class in Great Britain among males of working age.
The study was a cross sectional analysis of Registrar General's data for England and Wales around 1981, repeated for around 1971, and for Scotland around 1971 and 1981.
For England and Wales around 1971, suicide and undetermined death rates showed a progressive increase with age and a markedly higher rate in the lower social classes. A significant interaction effect was identified in the central age groups of the lower occupational categories. This interaction was confirmed in the remaining three data sets, notwithstanding some differences in the profile of age specific mortality. Other findings included a higher standardised mortality ratio for the economically inactive, who also showed an earlier peak in age specific mortality, and a relative concentration of undetermined as compared to suicide deaths in the lower social classes, but not all these further results were fully replicated.
There is a concentration of suicide and undetermined deaths in the middle age groups of the lower social classes. Plausible explanations include both the social drift and the social genesis hypotheses, the latter including the effects of long term unemployment.
Chronic alcohol consumption polarizes the immune response away from Th1-mediated cell-mediated immunity. In the present report we investigate the first onset of alteration in immune parameters during ethanol consumption in terms of changes in splenic leukocyte cellularity and surface phenotype as well as alterations in Th1 and Th2 function.
BALB/c and C57BL/6 mice were fed ethanol-containing liquid diets, were pair-fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum for up to 12 days. At intervals during the feeding period, splenic leukocytes were assessed for phenotypic markers by flow cytometry and for their ability to support antigen-induced interferon-gamma (IFNgamma) production in a coculture system. Mice were bled at intervals throughout the feeding period, and serum immunoglobin E (IgE) and alcohol levels were determined.
Data show that phenotypic and functional alterations occur within the first few days of alcohol consumption. Both liquid diets affect splenic cellularity, and by dietary day 5, ethanol-containing liquid diets further reduce B and NK cell numbers. The decline in B cells is accompanied by a concomitant decline in the amount of major histocompatibility complex class II expressed on this population. Functional alteration in Th1-mediated IFNgamma production occurred in the population fed ethanol-containing liquid diets by dietary day 5. Th2 function, as indicated by systemic serum IgE levels in these unimmunized mice, is increased by dietary day 6 to 8 and correlated with significant blood alcohol levels.
Ethanol consumption by mice causes a rapid decrease in splenic cellularity accompanied by a decrease in Th1 function and a rapid increase in systemic IgE levels.
Socioeconomic status (SES) is one of the most widely studied constructs in the social sciences. Several ways of measuring SES have been proposed, but most include some quantification of family income, parental education, and occupational status. Research shows that SES is associated with a wide array of health, cognitive, and socioemotional outcomes in children, with effects beginning prior to birth and continuing into adulthood. A variety of mechanisms linking SES to child well-being have been proposed, with most involving differences in access to material and social resources or reactions to stress-inducing conditions by both the children themselves and their parents. For children, SES impacts well-being at multiple levels, including both family and neighborhood. Its effects are moderated by children's own characteristics, family characteristics, and external support systems.
Linkage of atopy and associated traits to a locus on chromosome 13q14 has been identified by several studies in diverse populations. We have previously shown the putative atopy gene to be contained within an interval of approximately 5 Mb flanked by D13S328 and D13S1269 and centred on D13S273. We have now extended this work using a top-down approach to physical mapping. A YAC contig was constructed covering the D13S328 and D13S1269 interval. Thirty-one ESTs were mapped to the contig. We constructed a BAC and PAC contig flanking D13S273 by approximately 750 kb in either direction. The interval contained 27 of the 31 ESTS from the YAC contig. Seven previously unknown microsatellites were recovered and then typed in two subject panels. A positive association between the total serum Immunoglobulin E concentration and the novel USAT24G1 microsatellite was discovered (P(corrected)<0.005) and replicated in a second panel of families. The discovery of a region of positive association within the BAC/PAC contig will permit identification of the atopy gene from this locus.
To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child.
Prospective study.
Princess Anne Maternity Hospital, Southampton, UK.
A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years.
Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed.
There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy >75 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l.
Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies.
Genomic imprinting is a phenomenon by which the expression of an allele at a locus depends on the parent of origin. Two different two-locus evolutionary models are presented in which a second locus modifies the imprinting status of the primary locus, which is under differential selection in males and females. In the first model, a modifier allele that imprints the primary locus invades the population when the average dominance coefficient among females and males is >12 and selection is weak. The condition for invasion is always heavily contingent upon the extent of dominance. Imprinting is more likely in the sex experiencing weaker selection only under some parameter regimes, whereas imprinting by either sex is equally likely under other regimes. The second model shows that a modifier allele that induces imprinting will increase when imprinting has a direct selective advantage. The results are not qualitatively dependent on whether the modifier locus is autosomal or X linked.
Background:
Although alcohol consumption has been suggested to have an effect on the immune system, it is unknown whether alcohol consumption has a role in developing allergic diseases. We aimed to examine the associations of total alcohol intake during pregnancy with the risks of childhood asthma and atopic eczema in a birth cohort in Japan.
Methods:
Pregnant women were recruited at a maternal clinic from May 2000 to October 2001. The children who were born to these mothers were followed until November 2007. Total alcohol intake, including alcohol as a cooking ingredient, was assessed using 5-day dietary records. Mother reports of physician-diagnosed asthma and atopic eczema were annually obtained from the questionnaires. Asthma assessed by the American Thoracic Society Division of Lung Diseases questionnaire and atopic eczema assessed by International Study of Asthma and Allergies in Childhood questions were also obtained in 2007. A total of 350 children participated in the follow-up survey.
Results:
Maternal total alcohol intake during pregnancy was associated with increased risks of atopic eczema before age 3. The positive association with atopic eczema was also observed when it was defined as before age 5. In the high versus the low tertile of maternal total alcohol intake, the estimated hazard ratios (HRs) of child's eczema were 1.90 (95% CI: 0.96 to 3.76) before age 3 and 1.74 (95% CI: 0.93 to 3.24) before age 5, respectively. The estimated HRs of child's asthma before age 3 was 1.61 (95% CI: 0.70 to 3.69) in the high versus the low of maternal total alcohol intake and 2.11 (95% CI: 0.93 to 4.81) among children having drinking mothers versus nondrinking mothers in pregnancy, although maternal alcohol intake during pregnancy was not significantly associated with the risk of asthma before age 5.
Conclusions:
Alcohol consumption during pregnancy might have an effect on developing atopic eczema in offspring.
The role of socioeconomic position (SEP) in the development of asthma and allergies is unclear, with some pointing to the risks of low SEP and other research pointing in the direction of higher SEP being associated with higher prevalence rates. The aim of this systematic review is to clarify associations between SEP and the prevalence of asthma and allergies. Out of 4407 records identified, 183 were included in the analysis. Low SEP was associated with a higher prevalence of asthma in 63% of the studies. Research on allergies, however, showed a positive association between higher SEP and illness in 66% of studies. Pooled estimates for the odds ratio of disease for the highest compared with the lowest SEP confirmed these results for asthma (unadjusted OR 1.38, 95% CI 1.37-1.39), allergies in general (OR 0.67, 95% CI 0.62-0.72), atopic dermatitis (unadjusted OR 0.72, 95% CI 0.61-0.83) and allergic rhinoconjunctivitis (unadjusted OR 0.52, 95% CI 0.46-0.59). Sensitivity analyses with a subsample of high-quality studies led to the same conclusion. Evidence from this systematic review suggests that asthma is associated with lower SEP, whereas the prevalence of allergies is associated with higher SEP.
Copyright ©ERS 2014.
Background Considering the early onset of atopic dermatitis (AD), which most often arises in the first year of life, risk factors occurring very early in life must be considered. Little is known about the effects of maternal occupational exposure on the development of atopic disorders in children.
Objectives The aim of this study was to evaluate associations between maternal employment and childhood AD.
Methods We used multistage stratified systematic sampling to recruit 24 200 mother–newborn pairs from the Taiwan national birth register. Information on maternal occupation categories, work stress, working time, shift work and potential confounders during pregnancy was gathered by questionnaires after birth. At 3 years of age, information on the development of AD was assessed by home interviews. Multiple logistic regression analysis was performed to estimate the association of maternal employment and AD.
Results Overall, 11 962 out of 19 381 mothers (61·7%) worked during pregnancy. The children of mothers who worked during pregnancy had an increased risk of AD compared with those whose mothers did not work [odds ratio (OR) 1·38, 95% confidence interval (CI) 1·25–1·53]. The children of mothers with a professional or technical occupation had a higher risk of AD (OR 1·64, 95% CI 1·44–1·87). The risk of AD was found to increase with maternal work stress during pregnancy in a dose–response manner (Ptrend < 0·01). The mothers of children with AD had a longer working time than those without AD (P < 0·0001). However, no significant association between AD and maternal shift work was found.
Conclusions Working in professional or technical occupations increased the risk of childhood AD in addition to work stress during pregnancy.
To cite this article: Hicks WB, Nageotte CG, Wegienka G, Havstad S, Johnson CC, Ownby DR, Zoratti EM. The association of maternal prenatal IgE and eczema in offspring is restricted to non-atopic mothers. Pediatric Allergy Immunology 2011; 22: 684–687.
The risk of developing eczema is thought to be influenced by both genetic and environmental factors. Prenatal factors including the intrauterine environment may influence risk. We examined the relationship of maternal total IgE obtained during pregnancy to the incidence of atopic dermatitis in their 2-yr-old offspring. Subjects were participants in an unselected Detroit area birth cohort. Serum IgE was measured from 458 mothers in the third trimester of pregnancy along with prenatal family and environmental histories. Children were evaluated at approximately 2 yr of age for current or past eczema by maternal questionnaire and physician examination. Among the 458 children, 20.3% (n = 93) had a doctor confirmed diagnosis of eczema. Prenatal IgE was higher among women whose children developed AD vs. women whose children did not [Geometric means and 95% confidence intervals 52.7 IU/ml (40.9–68.0) vs. 32.9 IU/ml (28.0–38.7), p = 0.010]. The association was only seen in a subgroup of 181 women without allergic sensitization (specific IgE >0.35 IU/ml) to a panel of eight common allergens. Of the women without allergic sensitization, the mean serum IgE was 24.1 IU/ml (15.5–37.6) among those whose children had a diagnosis of eczema. The mean serum IgE was 11.2 IU/ml (9.2–13.6) among those whose children did not have a diagnosis of eczema (p-value 0.002). Maternal prenatal IgE level among women who are not sensitized to common allergens is associated with increased risk of eczema in offspring.
IgE dysregulation is a major pathogenic feature of atopic dermatitis and other IgE-mediated allergic diseases such as asthma and rhinitis. Allergen complexed to IgE binds to the high affinity receptor for IgE (Fc epsilon RI) on the surface of epidermal Langerhans cells, mast cells and basophils, triggering the release of inflammatory mediators. The beta subunit of Fc epsilon RI has been localized to human chromosome 11q12-13, and variants within this gene have been shown to associate with asthma and measures of atopy. We have tested several polymorphisms within Fc epsilon RI-beta for association to atopic dermatitis in a panel of 60 families (panel A), recruited through a proband with atopic dermatitis. The findings were tested in a second panel of families (panel B). Significant sharing of maternal alleles was seen for atopic dermatitis and allele 2 of RsaI intron 2 (RsaIvin2*2) (P = 0.0022) and allele 1 of RsaI exon 7 (RsaIvex7*1) (P = 0.0036) Fc epsilon RI-beta gene polymorphisms. These findings were replicated in Panel B, confirming the association of Fc epsilon RI-beta RsaI polymorphisms with atopic dermatitis. The combined significance of the association of atopic dermatitis to RsaI polymorphisms was P = 0.0002 (RsaIvin2*2) and P = 0.00034 (RsaIvex7*1). The polymorphisms also showed association with asthma: P = 0.0068 (RsaIvin2*2) and P = 0.018 (RsaIvex7*1). Polymorphisms within the Fc epsilon RI-beta gene are strongly associated with atopic dermatitis.
Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs.
We published a systematic review on atopic dermatitis (AD) and the hygiene hypothesis in 2005. Since then, the body of literature has grown significantly.
We therefore repeated our systematic review to examine the evidence from population-based studies for an association between AD risk and specific infections, childhood immunizations, the use of antibiotics and environmental exposures that lead to a change in microbial burden.
Medline was searched from 1966 until June 2010 to identify relevant studies.
We found an additional 49 papers suitable for inclusion. There is evidence to support an inverse relationship between AD and endotoxin, early day care, farm animal and dog exposure in early life. Cat exposure in the presence of skin barrier impairment is positively associated with AD. Helminth infection at least partially protects against AD. This is not the case for viral and bacterial infections, but consumption of unpasteurized farm milk seems protective. Routine childhood vaccinations have no effect on AD risk. The positive association between viral infections and AD found in some studies appears confounded by antibiotic prescription, which has been consistently associated with an increase in AD risk.
There is convincing evidence for an inverse relationship between helminth infections and AD but no other pathogens. The protective effect seen with early day care, endotoxin, unpasteurized farm milk and animal exposure is likely to be due to a general increase in exposure to non-pathogenic microbes. This would also explain the risk increase associated with the use of broad-spectrum antibiotics. Future studies should assess skin barrier gene mutation carriage and phenotypic skin barrier impairment, as gene-environment interactions are likely to impact on AD risk.
Several studies have investigated the association between socioeconomic status and the occurrence of allergies. Nevertheless, the results remain contradictory. The aim of this study was to evaluate the associations between parental education and the occurrence of atopic sensitization, recurrent wheezing and eczema during the first year of life, differentiating between atopic and non-atopic disorders based on specific serum IgE. We conducted an aetiological study in 690 children, based on a prospective birth cohort project in which environmental and health information was gathered using questionnaires. At the age of 1 yr a blood sample was taken for quantification of specific IgE. Adjusted odds ratios and 95% confidence intervals were computed as measures of association between the outcomes and parental education. Parental educational level was positively associated with the occurrence of atopic sensitization (OR: 2.1; 95% CI: 1.0-4.4) and eczema (OR: 1.9; 95% CI: 1.1-3.4), but negatively with the occurrence of recurrent wheezing (OR: 0.4; 95% CI: 0.2-0.8) in the first year of life. Atopic recurrent wheezing was positively associated with the education of the parents, whereas non-atopic recurrent wheezing was negatively associated. When maternal and paternal education were considered separately, only maternal education had a significant influence. Our results suggest that aspects associated with a high maternal educational level may play an important role in the development of atopic disorders.
Epigenetics is the study of differences in phenotype, in the absence of variation in the genetic code. Epigenetics is relevant in the pathogenesis of many skin diseases. In the case of the common skin cancers, aberrant methylation of tumor suppressor gene promoters is associated with their transcriptional inactivation. Environmental carcinogens such as ultraviolet radiation and arsenic may act through epigenetic mechanisms. Hypomethylation is associated with activation of systemic autoimmune diseases, such as systemic lupus erythematosus, subacute cutaneous lupus erythematosus and scleroderma. This may be through a mechanism of immunological cross-reactivity with hypomethylated DNA from pathogenic bacteria. Epigenetic factors may also be relevant in the pathogenesis of psoriasis and other inflammatory skin diseases, as well as in the pathogenesis of the disorders of genomic imprinting with cutaneous features.
The risk of infantile atopic dermatitis (AD) posed by maternal atopy and paternal atopy, respectively, were compared in the infants from a birth cohort in whom one of the parents had been designated atopic by skin prick testing. Nineteen with atopic mothers were compared with 20 with atopic fathers. AD, other atopic manifestations and potentially influential factors such as breast-feeding were documented prospectively during the first year in all infants. At 3, 6 and 12 month assessments skin prick sensitivity and total serum IgE concentration were determined. Nine of 19 infants with atopic mothers and two of 20 with atopic fathers had AD (P = 0.023) giving a relative risk of 4.7 (95% confidence interval 2.5 to 9.0). Seven of 19 with atopic mothers and none with atopic fathers had AD with onset before 6 months (P = 0.007). When all types of disease evidence (AD, recurrent wheeze and food reactions) were analysed together no significant difference was apparent between the groups. The two groups were found to be well matched with regard to breast-feeding, time of starting cow's milk, solids and egg, sex, month of birth, parental AD and smoking, race, household pets and neonatal IgE concentration. IgE concentrations at each age and the prevalence of skin prick positivity were similar between the groups. Maternal atopy poses a higher risk for infantile AD and paternal atopy. Whether this may be due to genetic or congenital factors or both is uncertain, but clearly the finding is of relevance in the prediction of allergy in childhood.
We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma.
To determine whether the increased prevalence of childhood eczema in advantaged socioeconomic groups is due to increased parental reporting.
Comparison of parental reports of eczema with visible eczema recorded by medical officers during a detailed physical examination.
National birth cohort study.
8279 children from England, Wales, and Scotland born during 3-9 March 1958 and followed up at the ages of 7, 11, and 16.
Prevalence of eczema according to parental report compared with medical officer's examination at the ages of 7, 11, and 16.
Prevalence of both reported and examined eczema increased with rising social class at the ages of 7, 11, and 16 years. The point prevalence of examined eczema at age 7 was 4.8%, 3.6%, 3.6%, 2.4%, 2.2%, and 2.4% in social classes I, II, III non-manual, III manual, IV, and V respectively (chi 2 value for linear trend 12.6, P < 0.001). This trend persisted after adjustment for potential confounders such as region and family size and was not present for examined psoriasis or acne.
Eczema is more prevalent among British schoolchildren in social classes I and II than those in lower classes. Exposures associated with social class are probably at least as important as genetic factors in the expression of childhood eczema.
Maternal smoking during pregnancy has been shown to lead to immunologic changes in the offspring. However, little is known about the influence of this exposure on atopic manifestations.
Our purpose was to investigate the influence of air pollutants on manifestations of atopy in preschool children.
Unselected cohorts of a total of 678 5- to 6-year-old preschool children (350 boys, 328 girls) were investigated in areas with different degrees of air pollution in Bavaria. Data on the history of atopic diseases and other relevant factors were obtained by questionnaire. A skin-prick test was performed with common aeroallergens. Manifestation of atopy was defined as personal history of atopic disease or positive prick test to either grass pollen, house dust mite, or cat and analyzed multivariately.
Of all children, 38.9% exhibited at least one manifestation of atopy. Atopic eczema was reported in 7.9% to 15.5%, hayfever in 4.1% to 25.6%, and asthma in 3.0% to 8.1%. Of the mothers, 12.6% smoked during pregnancy or lactation or both. Analysis of the manifestation of atopy including sex, location, nitrogen oxide and sulfur dioxide exposure and maternal smoking as covariates revealed an influence of the maternal smoking during pregnancy/lactation. Of children whose mothers had smoked during pregnancy/lactation, 52.2% exhibited manifestations of atopy in contrast to 35.7% of children of nonsmoking mothers (p < 0.044). A history of atopic eczema was the only component of the variable "manifestation of atopy" that was significantly associated with maternal smoking during pregnancy and lactation. A causal interpretation of this finding, however, was not supported by a follow-up study.
Maternal smoking during pregnancy or lactation or both might play a role in the development of atopic eczema and should be avoided.
Recent research consistently reports that persistent poverty has more detrimental effects on IQ, school achievement, and socioemotional functioning than transitory poverty, with children experiencing both types of poverty generally doing less well than never-poor children. Higher rates of perinatal complications, reduced access to resources that buffer the negative effects of perinatal complications, increased exposure to lead, and less home-based cognitive stimulation partly account for diminished cognitive functioning in poor children. These factors, along with lower teacher expectancies and poorer academic-readiness skills, also appear to contribute to lower levels of school achievement among poor children. The link between socioeconomic disadvantage and children's socioemotional functioning appears to be mediated partly by harsh, inconsistent parenting and elevated exposure to acute and chronic stressors. The implications of research findings for practice and policy are considered.
To investigate the association between social circumstances in childhood and mortality from various causes of death in adulthood.
Prospective observational study.
27 workplaces in the west of Scotland.
5645 men aged 35-64 years at the time of examination.
Death from various causes.
Men whose fathers had manual occupations when they were children were more likely as adults to have manual jobs and be living in deprived areas. Gradients in mortality from coronary heart disease, stroke, lung cancer, stomach cancer, and respiratory disease were seen (all P<0.05), generally increasing from men whose fathers had professional and managerial occupations (social class I and II) to those whose fathers had semiskilled and unskilled manual occupations (social class IV and V). Relative rates of mortality adjusted for age for men with fathers in manual versus non-manual occupations were 1.52 (95% confidence interval 1.24 to 1.87) for coronary heart disease, 1.83 (1.13 to 2. 94) for stroke, 1.65 (1.12 to 2.43) for lung cancer, 2.06 (0.93 to 4. 57) for stomach cancer, and 2.01 (1.17 to 3.48) for respiratory disease. Mortality from other cancers and accidental and violent death showed no association with fathers' social class. Adjustment for adult socioeconomic circumstances and risk factors did not alter results for mortality from stroke and stomach cancer, attenuated the increased risk of coronary heart disease and respiratory disease, and essentially eliminated the association with lung cancer.
Adverse socioeconomic circumstances in childhood have a specific influence on mortality from stroke and stomach cancer in adulthood, which is not due to the continuity of social disadvantage throughout life. Deprivation in childhood influences risk of mortality from coronary heart disease and respiratory disease in adulthood, although an additive influence of adulthood circumstances is seen in these cases. Mortality from lung cancer, other cancer, and accidents and violence is predominantly influenced by risk factors that are related to social circumstances in adulthood.
Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onset mainly in early childhood It is commonly the initial clinical manifestation of allergic disease, often preceding the onset of respiratory allergies. Along with asthma and allergic rhinitis, atopic dermatitis is an important manifestation of atopy that is characterized by the formation of allergy antibodies (IgE) to environmental allergens. In the developed countries, the prevalence of atopic dermatitis is approximately 15%, with a steady increase over the past decades. Genetic and environmental factors interact to determine disease susceptibility and expression, and twin studies indicate that the genetic contribution is substantial. To identify susceptibility loci for atopic dermatitis, we ascertained 199 families with at least two affected siblings based on established diagnostic criteria. A genome-wide linkage study revealed highly significant evidence for linkage on chromosome 3q21 (Zall=4.31, P= 8.42 10(-6)). Moreover, this locus provided significant evidence for linkage of allergic sensitization under the assumption of paternal imprinting (hlod=3.71,alpha=44%), further supporting the presence of an atopy gene in this region. Our findings indicate that distinct genetic factors contribute to susceptibility to atopic dermatitis and that the study of this disease opens new avenues to dissect the genetics of atopy.
We have carried out a genome screen for atopic dermatitis (AD) and have identified linkage to AD on chromosomes 1q21, 17q25 and 20p. These regions correspond closely with known psoriasis loci, as does a previously identified AD locus on chromosome 3q21. The results indicate that AD is influenced by genes with general effects on dermal inflammation and immunity.
Although atopic eczema (AE) is a common disease, little is known about its causes.
To investigate the role of dietary and environmental factors associated with the development of AE by the age of 2 years.
A cohort of children was recruited before birth from a consecutive series of newly pregnant mothers presenting for antenatal care at three general practices in Ashford, Kent, U.K. Data up to the age of 2 years were available for 624 (97%) of the original cohort. AE was defined using components of the U.K. diagnostic criteria for AE, maternal report of doctor-diagnosed eczema and maternally reported eczema. Exposures of interest were family history of allergic disease, dietary and breastfeeding patterns, family size and exposure to indoor domestic allergens.
The cumulative prevalence of AE using the U.K. diagnostic criteria was 14% (95% confidence interval, CI 11-17%). The prevalence of maternally reported doctor-diagnosed eczema was much higher (31%, 95% CI 27-35%) and almost half (45%) the mothers reported that their child had ever had eczema (95% CI 41-49%). The relationship between parental atopy, parental history of allergic disease and the child's eczema was consistently stronger for the mothers than the fathers. There was a marked increase in the prevalence of eczema with increasing maternal education and in less crowded homes, associations that remained significant after controlling for other factors.
The associations with environmental factors are consistent with the hypothesis that more crowded houses, increased family size and birth order, which may possibly increase early exposure to infections, may offer protection from subsequent development of eczema.
Atopic dermatitis is a hereditary, pruritic, inflammatory and chronic skin disease that typically presents in early childhood and may continue or recur later. The etiology of atopic dermatitis is unknown, but several lines of evidence indicate that it is a multifactorial disorder caused by the combined influence of genetic and environmental factors, even though the relative contributions of genes and environment are not known. To identify important loci that contribute to the development of atopic dermatitis, we conducted a genome-wide linkage analysis with 367 microsatellite markers, using a non-parametric affected relative-pair method in 109 pedigrees. Three qualitative phenotypes and one semi-quantitative phenotype were studied. For the phenotype atopic dermatitis, linkage to chromosome region 3p24-22 was found. For another phenotype, atopic dermatitis combined with raised allergen-specific IgE levels, a suggestive linkage was found to chromosome region 18q21. For the semi-quantitative phenotype severity score of atopic dermatitis, suggestive linkage was found to chromosome regions 3q14, 13q14, 15q14-15 and 17q21. Identifying chromosome regions linked to susceptibility genes for atopic dermatitis provides a platform from which the search for atopic dermatitis genes can proceed.
The aetiology of atopic dermatitis (AD) is presumably multi-factorial, with interactions between genetic and environmental factors.
To investigate the relation between atopic family history and development of AD up to 4 years.
Using annual questionnaires, we studied the cumulative incidence of AD in 0-4-year-olds in a prospective birth cohort of 4089. Atopic diseases in parents and siblings were recorded at birth. The occurrence of serum immunoglobulin E (IgE) antibodies to inhalant and food allergens was analysed in 2614 4-year-olds, and AD was divided into non-IgE-associated and IgE-associated.
Of the children without atopic parents, 27.1% developed AD; of those with single or double parental atopic history, 37.9% and 50.0%, respectively, did so. The effects of parental history of eczema and of atopic respiratory disease (ARD) did not differ significantly, nor did those of maternal and paternal history. Parental history of ARD increased the risk significantly more for IgE-associated AD than for non-IgE-associated AD (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.5-2.8 vs. OR 1.3; 95% CI 1.0-1.8), whereas the two forms lacked major differences in the effect of parental eczema. A history of eczema in older siblings was a risk indicator for both forms of AD (OR 2.1; 95% CI 1.4-3.3 vs. OR 1.8; 95% CI 1.2-2.6).
We found no difference between the effects of maternal and paternal atopic history. Parental eczema was a risk factor for AD irrespective of its association with IgE, but parental history of ARD mainly increased the risk of IgE-associated AD.
The atopic history of parents has long been used to predict infant atopy. However, bias from questionnaires of allergic history are also frequently suspected, because a large number of vasomotor rhinitis, intrinsic asthma, and seborrheic dermatitis cases are probably misinterpreted to be atopic diseases.
We attempted to identify a risk factor other than parental atopic history to predict elevated infant IgE levels and infant atopy.
A total of 655 core families were prenatally recruited, and finally 545 families completed the study for the prospective analysis of infant atopy at 6 months of age. Atopic history and blood samples of parents were collected in the third trimester during pregnancy. Cord blood (CB) was collected immediately after birth. Infant blood samples and history of infant eczema were collected in the 6-month physical checkup clinic. Blood total IgE and specific IgE levels were determined by use of the Pharmacia CAP system.
In univariate analysis, maternal, but not paternal, atopic history correlated with elevated CB IgE levels and the occurrence of infant eczema. Elevated maternal, but not paternal, total IgE levels (>150 KU/L) significantly correlated with increases of CB IgE levels (median, 0.54 vs 0.17 KU/L, P <.001), infant IgE levels (log-transformed mean values, 1.32 +/- 0.51 vs 1.13 +/- 0.51 KU/L, P <.001), and infant eczema (P =.008). Multivariate logistical regression analysis, however, showed that only maternal total IgE levels correlated with CB and infant IgE levels and the development of infant eczema.
The maternal, but not paternal, total IgE level correlates with elevated infant IgE levels and infant atopy. This provides a high specificity (83%) and a sensitivity of 34% for prediction of infant atopy. This suggests that maternal factors, placental factors, or both have an impact on perinatal allergic sensitization.
To evaluate the association of parental history of atopic disease with childhood atopic dermatitis, and to examine the relative strength of associations with maternal and paternal disease.
Mothers were recruited to the Avon longitudinal study of parents and children (ALSPAC) from the eighth week of pregnancy. Before parturition, both parents were asked, separately, to report their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms of atopic dermatitis in their children at ages 6, 18, 30, and 42 months.
Of 8530 children with complete information on rash at ages 6, 18, 30, and 42 months, 7969 had complete information on maternal atopic disease and 5658 on maternal and paternal atopic disease. There was a strong association between parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents. Associations with parental asthma or hayfever were attenuated after controlling for parental eczema. There was no evidence that associations with maternal atopy were stronger than with paternal.
Associations between parents' atopic disease and the risk of atopic dermatitis in offspring vary according to the type of atopic disease in the parents, but not according to parental sex. These results are at variance with previous studies reporting stronger associations with maternal than paternal atopy, and suggest that there is no "parent-of-origin" effect in atopic dermatitis. Parental eczema may be a better marker than parental asthma/hayfever in predisposing to childhood eczema.
Atopic Dermatitis (AD), hayfever and asthma are commonly summarized as atopic diseases. The spatial distribution of AD differs from that of asthma and hayfever, suggesting that AD might follow a different risk pattern than these diseases. AD can be differentiated into an allergic extrinsic form (EAD) and a non-allergic intrinsic form (IAD). Only EAD might follow the distribution and risk pattern that have been ascribed to asthma and hayfever.
To investigate the distribution and risk factor profile of AD and EAD focusing on environmental factors relating to the hygiene hypothesis.
Population-based cross-sectional study on 12,601 children aged 5-7 and 9-11 years from Dresden (Eastern Germany) and Munich (Western Germany). Information was obtained by International Study of Asthma and Allergic Childhood questionnaires, dermatological examinations and skin prick testing. AD-diagnosis ever, current AD-symptoms and visible eczema were investigated with their respective extrinsic forms.
Maternal and paternal history of AD were equally strong determinants of the child's AD status. Factors related to the hygiene hypothesis like day-care attendance and number of older siblings were not associated with a decreased risk of AD. The proportion of EAD within AD was higher in Eastern than in Western Germany. The determinants of the diseases appeared to be similar for both EAD and IAD.
There was no evidence of the hygiene hypothesis holding true for AD or EAD. AD might be a separate entity than respiratory atopic diseases. Little is known about the risk factors of AD and factors different from those of respiratory allergic diseases should be considered in future research.
Among early-life environmental factors, parental smoking (ETS) has been associated with adverse respiratory outcomes in children. The aim of the study was to evaluate whether parental smoking might lead to asthma and allergies taking into account family history of asthma, personal atopy, breast feeding as confounders and owing pets and day-care during the first 6 months of life as modifiers. About 9000 children of fourth and fifth grade were selected in six cities of France. About 7798 answered an epidemiological questionnaire, underwent a medical examination including skin prick test positivity to common allergens, skin examination for eczema, and run test to assess exercise-induced asthma (EIA). Prevalence of allergies was, respectively, 25.2% for eczema, 12.9% for rhinitis, 9.9% for asthma and 25% for atopy. About 8.3% had an EIA. About 21.6% of children were exposed to maternal tobacco smoking during pregnancy. Maternal smoking, in utero and later, was significantly related to lifetime wheezing (odds ratio (OR): 1.24[1.10-1.56]) and asthma (OR: 1.22[1.04-1.66]). There was no association between atopy, rhinitis, eczema and parental smoking, respectively. ETS remains a risk factor of wheezing in childhood. Counselling parents of children to quit smoking still remains a public health policy.
Allergy and asthma risk share strong inherited components; however, the relative importance of maternal and paternal atopy in predicting child atopy remain unclear.
We sought to identify relationships between parents' and children's total and specific IgE levels within family units as predictors of allergic risk in children.
Total and allergen-specific IgE (to dust mite, cockroach, mouse, and cat) were determined by means of ImmunoCap (Phadia, Inc, Portage, Mich) in a sample of families participating in New York City Head Start programs. Regression models were developed to determine the associations of parents' and children's total IgE levels and sensitization patterns.
Blood specimens were collected from 161 family triads of mother, father, and child (83 boys and 78 girls). At a mean age of 4 years, boys had significantly higher total IgE levels than girls. Boys' total IgE levels were highly correlated with both mothers' (P < .002) and fathers' (P = .002) total IgE levels; girls' total IgE levels were not. Unlike total IgE levels, specific IgE levels among both boys and girls were associated with their mothers' specific IgE levels. Dust mite sensitization among mothers was predictive of children's sensitization to each of the 4 aeroallergens.
The strong associations between parents' and children's IgE levels suggest that assessment of parents' total and locally relevant allergen-specific IgE levels might have value in predicting atopy in children of preschool age.
The genetics of atopic dermatitis