Risk Factors For Atopic Dermatitis Research Articles

Atopic dermatitis in children aged 1 - 7 years in Shenzhen city: an epidemiological study

Objective To investigate the prevalence of and influencing factors for atopic dermatitis (AD) in children aged 1 - 7 years in Shenzhen city, and to analyze difference in diagnostic results between two diagnostic criteria. Methods From December 1st 2013 to March 1st 2014, a questionnaire survey and physical examination were conducted to investigate the prevalence of AD in children aged 1 - 7 years in Shenzhen city. Results A total of 1 504 children were enrolled into this study, including 716 males and 788 females. Based on the clinical diagnosis by experienced dermatologists, the prevalence of AD was 11.84% (178/1 504) in total, 11.73% (84/716) and 11.93% (94/788) in males and females, respectively, and there was no significant difference in the prevalence of AD between males and females (χ2 = 0.01, P > 0.05) . Based on the Williams′ diagnostic criteria, the prevalence of AD was 3.92% (59/1 504) in total, and 4.05% (29/716) and 3.81% (30/788) in males and females, respectively. Premature birth was a risk factor for the occurrence of AD (χ2 = 5.43, P < 0.05) . Conclusions The prevalence of AD is evidently increased among children aged 1 - 7 years in Shenzhen city, and premature birth is a risk factor for AD. Missed diagnosis will be reduced based on clinical diagnosis by experienced dermatologists. Key words: Dermatitis, atopic; Child; Prevalence; Population characteristics

Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts

BackgroundAtopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms.ObjectivesWe sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts.MethodsThe presence of AD was examined in 2 birth cohort studies including 9894 children from the United Kingdom (ALSPAC) and 3652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity.ResultsSix latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the 2 cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male sex. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognized class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.ConclusionsSix classes based on temporal trajectories of rash were consistently identified in 2 population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.

Maternal sensitivity and social support protect against childhood atopic dermatitis

BackgroundMany studies have identified associations between qualities of maternal–child relationships and childhood asthma, but few have examined associations with childhood atopic dermatitis (AD), a common precursor to asthma. Moreover, maternal psychological distress, including prenatal and postnatal depression, anxiety and stress, may increase risk, while social support from partners may reduce risk for childhood AD. We sought to uncover the association between maternal–infant relationship qualities (maternal sensitivity towards infant behavioral signals, controlling behavior, and unresponsiveness) and child AD after accounting for risk (i.e., prenatal and postnatal maternal depression, anxiety and stress) and protective (i.e., social support) factors.MethodsWe conducted a secondary analysis of data collected on a subsample of 242 women and their infants enrolled during pregnancy in the ongoing Alberta Pregnancy Outcomes and Nutrition cohort study. Inclusion criteria required mothers to be >16 years of age, English speaking and <22 weeks gestational age at enrollment. Data on depression, anxiety and stress in the prenatal and postnatal periods and physician diagnosis of childhood AD at 18 months were gathered via maternal report. Maternal sensitivity, unresponsiveness and controlling behaviours were assessed via videotaped observations using the Child-Adult Relationship Experimental (CARE)-Index at 6 months of infant age.ResultsHigher maternal sensitivity, or the inability of the mother to appropriately understand and respond to infant needs based on behavioral signals, predicted reduced odds of AD independent of and in combination with low prenatal and postnatal anxiety and high paternal support. After adjustment, higher maternal controlling behaviours and unresponsiveness also predicted greater odds of AD.ConclusionsLow maternal sensitivity is a risk factor for childhood AD, independently and in combination with perinatal anxiety and low social support. Thus, interventions that improve maternal–infant relationship quality, especially sensitivity, reduce anxiety and improve social support from partners could reduce odds of childhood AD.

Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: results from two cross-sectional studies.

Common loss-of-function mutations in filaggrin gene (FLG) represent a strong genetic risk factor for atopic dermatitis (AD). Homozygous mutation carriers typically display ichthyosis vulgaris (IV) and many have concomitant AD. Previously, homozygous, but not heterozygous, filaggrin gene mutations have been associated with squamous cell carcinomas. The first objective was to examine the association between FLG mutations and actinic keratosis (AK). The second objective was to investigate the occurrence of AK in patients with IV and AD, respectively. FLG mutation status in patients with AK was compared with controls from the general population. Furthermore, based on nationwide data from Danish registers, we compared the risk of AK in patients with IV, AD and psoriasis, respectively. The prevalence of homozygous FLG mutations was significantly higher in the AK group (n = 4, 0.8%) in comparison with the control group (n = 18, 0.2%), whereas the prevalence of heterozygous FLG mutations was lower. In hospital registry data, patients with AD exhibited an increased risk of AK than did psoriasis controls (adjusted OR 1.46; [95% CI 1.12-1.90]), whereas no difference in risk was observed between patients with IV and AD. This study indicates an increased susceptibility to AK in individuals with homozygous, but not heterozygous, FLG mutations and in patients with AD compared to psoriasis. Whether a reduction or absence of epidermal filaggrin could contribute to the susceptibility to AK in patients with IV and AD is unknown and additional research is needed to further explore this relationship.

Insufficient physical activity is a risk factor of atopic dermatitis in Korean adolescents

Insufficient physical activity is a risk factor of atopic dermatitis in Korean adolescents

Identification of novel candidate variants including COL6A6 polymorphisms in early-onset atopic dermatitis using whole-exome sequencing

BackgroundThe prevalence of atopic dermatitis has increased over the last 10 years. Atopic dermatitis tends to run in families and commonly begins to manifest in childhood. The prevalence of atopic dermatitis is as high as 20% in children. Thus, early diagnosis and treatment of atopic dermatitis are important. Understanding its genetic basis is also needed to facilitate early detection.MethodsTo identify family-specific candidate genetic variants associated with early-onset atopic dermatitis in Koreans, we carried out whole-exome sequencing of three separate families with this condition. Additional validation was performed in 112 AD patients and 61 controls using Sanger sequencing.ResultsWe focused on both common functional variants with a minor allele frequency higher than 1% and rare variants with a minor allele frequency less than 1%. The relevance of the respective variants was supported by a program that could predict whether the mutations resulted in damaged protein function. Fourteen overlapping genes were identified during exome sequencing. Three variants of the COL6A6 gene appeared in all three families and were in close proximity to atopic dermatitis-related loci on chromosome 3q21. The homozygous frequency for the rs16830494 minor allele (AA) and the rs59021909 (TT) allele and the rs200963433 heterozygous (CT) frequency were all higher in AD cases compared to controls in a population-based case-control study.ConclusionIdentifying family-specific COL6A6 polymorphisms and genetic variants of other candidate genes associated with AD using WES is a novel approach. Our study suggests that COL6A6 variants may be risk factors for atopic dermatitis. This study provides a genetic basis for early-onset AD diagnosis in Korean patients and the development of new therapies.Trial registrationTrial registration number: IRB NO. C2008030 (133); Name of registry: The collection research of clinical data and patient blood to identify genetic and protein biomarker of atopic dermatitis; Date of registration: 09-July-2008.Trial registration number: IRB NO. C2015258 (1716); Name of registry: The collection study of patient blood and clinical data for the development of the prognosis prediction and early diagnosis of atopic dermatitis; Date of registration: 15-jan-2016.

Analysis of Epidemiology and Risk Factors of Atopic Dermatitis in Korean Children and Adolescents from the 2010 Korean National Health and Nutrition Examination Survey.

Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease, but only few studies involved samples of children and adolescents that are representative of the entire Korean population. This study aimed to estimate the prevalence and risk factors of AD among children and adolescents in Korea by using nationally representative data. Methods We used data from the fifth Korean National Health and Nutrition Examination Survey in 2010 and retrospectively evaluated 2,116 children and adolescents. Logistic regression analysis was performed to determine the relationship between AD and other variables, including IgE levels. Results The prevalence rate of AD in children and adolescents was 15.0%. In the multivariate analysis of ages from 1 to 18 years, age (adjusted odds ratio [aOR], 0.96; p < 0.01) was related to AD. From age of 12 to 18 years, smoking (aOR, 8.99; p < 0.01) and elevated total IgE serum level (aOR, 5.31; p < 0.01) were related to AD. Conclusion Age, smoking, and elevated total IgE level were related to AD in the children and adolescents. Thus, an antismoking policy and public education are necessary for reducing the prevalence of allergic diseases. In addition, measurement of total IgE level and age may be helpful in the diagnosis of AD.

Atopic Dermatitis: Disease Background and Risk Factors.

Multiple risk factors have been associated with the development of atopic dermatitis (AD). Recent advances in understanding the role of genetics in this disease have been made, with discovery of the filaggrin (FLG) gene as the most notable so far. In addition to FLG gene mutations as a risk factor for AD, a positive family history of atopic or allergic disease in either parent, has been shown to confer a greater risk of developing AD. Atopic dermatitis usually presents early in life and is thought to represent the initial-step in the "atopic march" which is characterized by the development of other atopic diseases later in life such as asthma, allergic rhinitis and/or rhinoconjunctivitis, food allergies and hay fever. Other comorbid diseases that have been associated with AD include increase risk of viral and bacterial skin infections, neuropsychiatric diseases such as attention-deficit hyperactivity disorders (ADHD) and autistic spectrum disorder (ASD). Patients with AD, have also been found to have worse sleep quality overall compared to patients without AD. In this chapter, we will discuss the risk factors associated with development of atopic dermatitis as well as the most commonly reported comorbidities in patients with this disease.

The Value of FLG Null Mutations in Predicting Treatment Response in Atopic Dermatitis: An Observational Study in Finnish Patients.

The contribution of filaggrin null mutations to predicting atopic dermatitis (AD) treatment response is not clear, nor have such mutations been studied in the Finnish population. This study tested the association of the 4 most prevalent European FLG null mutations, the 2 Finnish enriched FLG null mutations, the FLG 12-repeat allele, and 50 additional epidermal barrier gene variants, with risk of AD, disease severity, clinical features, risk of other atopic diseases, age of onset, and treatment response in 501 patients with AD and 1,710 controls. AD, early-onset AD, palmar hyperlinearity, and asthma showed significant associations with the combined FLG null genotype. Disease severity and treatment response were independent of patient FLG status. Carrier frequencies of R501X, 2282del4, and S3247X were notably lower in Finns compared with reported frequencies in other populations. This data confirms FLG mutations as risk factors for AD in Finns, but also questions their feasibility as biomarkers in predicting treatment response.

Association Between Metabolic Syndrome and Atopic Dermatitis in Korean Adults.

Whether metabolic syndrome (MetS) and its components are risk factors for atopic dermatitis (AD) remains unclear. This study investigated the association between MetS and AD in Korean adults. Nationally representative data for 5,007 Korean adults, aged 19-40 years, from the cross-sectional Korea National Health and Nutrition Examination Survey 2010-2011 were analysed. AD in female patients was associated with MetS (p = 0.02) and increased triglyceride level (p = 0.05). After adjusting for confounding factors, the odds ratio for female participants with MetS was 2.92; for central obesity (waist circumference ≥ 85 cm), 1.73; and for hypertriglyceridaemia, 2.20. In this large-scale nationwide study in Korean adults, MetS and its components (central obesity and hypertriglyceridaemia) correlated positively with the presence of AD in women.

ФАКТОРЫ МАКРОУРОВНЯ, ВЛИЯЮЩИЕ НА ПОКАЗАТЕЛЬ ЗАБОЛЕВАЕМОСТИ АТОПИЧЕСКИМ ДЕРМАТИТОМ У ДЕТЕЙ

Research purpose. To establish the macro-level socio-economic factors influencing the incidence rate of atopic&nbsp;dermatitis among the child population of the Grodno region.Material and methods. We used the data of the official statistical reporting of the Grodno Regional Department of&nbsp;Statistics, annual report forms «Form 1 – children» provided by the medical statistics office of the Grodno RegionalClinical Children's Hospital for the period of 2000–2013 years.Results. The factorial analysis revealed 3 main factors influencing the incidence rate of atopic dermatitis among&nbsp;children aged 0–14 years during 2000–2013: the factors characterizing the population’s level of living; the factors&nbsp;of living conditions; medico-demographic factors in combination with the factors of the population’s level of living.The regression equations demonstrating the relationship between the incidence rate of atopic dermatitis and the&nbsp;established factors are presented.Conclusion. The received results can serve as the basis for the directed analysis of regional risk factors of atopic&nbsp;dermatitis in children.

Home Remodeling and Food Allergy Interact Synergistically to Increase the Risk of Atopic Dermatitis

Purpose The purpose of this study was to investigate the effects of home remodeling and food allergy (FA) on the development of atopic dermatitis (AD) in children. Methods The Modified International Study of Asthma and Allergies in Childhood questionnaire was used to survey 4,111 children recruited from 3 kindergartens and 6 elementary schools from Seongnam, Korea. Participants' parents agreed for them to participate in physical examinations, skin prick tests, and blood tests. Results Home remodeling in the past 12 months (adjusted odds ratio [aOR] 3.40, P = 0.006), lifetime diagnosis of FA (aOR 3.95, P < 0.001), parental history of AD (aOR 2.67, P = 0.001), and FA (aOR 2.35, P = 0.004) were independent risk factors for lifetime diagnosis of AD ever. When history of home remodeling and FA were combined, the risk for moderate-to-severe AD by scoring atopic dermatitis (SCORAD) score increased (aOR, 7.19, P = 0.011, P for interaction = 0.034). Conclusion Home remodeling, lifetime diagnosis of FA, parental history of AD, and parental history of FA were independent risk factors for AD. In addition, we observed a synergistic interaction between home remodeling and FA in the risk of moderate-to-severe AD.

Desmosomes and corneodesmosomes and their relevance to genetic skin diseases.

Desmosomes are critical intercellular junctions between keratinocytes in the living cell layers of the epidermis. When the cells are differentiated and become cornified cells, desmosomes are transformed into corneodesmosomes. Distribution patterns of corneodesmosomes change with cell development. Namely, in the lower stratum corneum, corneodesmosomes are seen all around the cell membrane, but in the upper layers, they are only found at the edges of the flattened cells. Recently, it has been proposed that tight junction-derived structures are involved in this unique distribution of corneodesmosomes by protecting corneodesmosome degradation from proteases. Various types of skin diseases can be caused by abnormalities in the genes encoding components of desmosomes and corneodesmosomes or regulators of the proteolytic processing of these structures. Their clinical symptoms vary greatly: palmoplantar keratoderma on the pressure points, syndromic ichthyosis associated with atopic manifestations, diffuse keratoderma with cardiomyopathy, lethal epidermolysis bullosa, hair abnormalities, or a combination of these symptoms. Polymorphisms in some of the genes are risk factors for atopic dermatitis. Genetic diseases of desmosomes and corneodesmosomes are rare, but by studying them we will be enlightened about pathological mechanisms of more common multifactorial skin diseases such as atopic dermatitis.

Association between sleep duration and the prevalence of atopic dermatitis and asthma in young adults.

Sleep duration affects allergic diseases; however, this association requires further investigation. To evaluate the association between sleep duration and the prevalence of atopic dermatitis and asthma in young Korean adults. We analyzed data of 10,148 subjects (4,239 men; 5,909 women) aged 19-39 years from the Korean National Health and Nutrition Examination Survey 2008-2010. Self-reported sleep duration was categorized into five groups: ≤5h, 6h, 7h, 8h, and ≥9h. The prevalence of atopic dermatitis and asthma was examined based on a questionnaire and compared between participants from five sleep duration groups after adjusting for potential confounding factors, including model 1 [age], model 2 [model 1 + BMI, current smoking, current alcohol use, regular physical activity, household income, and serum 25(OH)D level], and model 3 [model 2 + stress levels]. In female participants, a higher risk of atopic dermatitis was associated with sleep duration ≤5 hours [odds ratio (OR): 1.665, 95% confidence interval (CI): 1.004-2.762; model 1], and ≥9 hours (OR, 1.746, 95% CI, 1.145-2.661; model 3), compared to a 7-hour sleep duration. Similarly, a higher risk of asthma was associated with sleep duration ≤5 hours and ≥9 hours (OR, 1.553, 95% CI, 1.023-2.359 and OR, 1.569, 95% CI, 1.048-2.349, respectively; model 3). In male participants, there was no significant association between sleep duration and the prevalence of atopic dermatitis or asthma. Sleep duration ≤5 and ≥9 hours may be a risk factor for atopic dermatitis and asthma in young female adults.

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

Loss-of-function mutations in the FLG gene cause ichthyosis vulgaris (IV) and represent the major predisposing genetic risk factor for atopic dermatitis (AD). Although both conditions are characterized by epidermal barrier impairment, AD also exhibits signs of inflammation. This work was aimed at delineating the role of FLG loss-of-function mutations on eicosanoid metabolism in IV and AD. Using human epidermal equivalents (HEEs) generated with keratinocytes isolated from nonlesional skin of patients with FLG wild-type AD (WT/WT), FLG-mutated AD (FLG/WT), IV (FLG/FLG), or FLG WT control skin, we assessed the potential autocrine role of epidermal-derived eicosanoids in FLG-associated versus FLG-WT AD pathogenesis. Ultrastructural analyses demonstrated abnormal stratum corneum lipid architecture in AD and IV HEEs, independent of FLG genotype. Both AD (FLG/WT) and IV (FLG/FLG) HEEs showed impaired late epidermal differentiation. Only AD (FLG/WT) HEEs exhibited significantly increased levels of inflammatory cytokines. Analyses of lipid mediators revealed increased arachidonic acid and 12-lipoxygenase metabolites. Whereas treatment of control HEEs with arachidonic acid increased expression of inflammatory cytokines, 12-hydroxy-eicosatetraenoic acid attenuated expression of late differentiation markers. Thus, FLG mutations lead to alterations in epidermal eicosanoid metabolism that could serve as an autocrine trigger of inflammation and impaired late epidermal differentiation in AD.

Gram-positive anaerobe cocci are underrepresented in the microbiome of filaggrin-deficient human skin

Mutations in the filaggrin gene, which cause the skin disease ichthyosis vulgaris and are a genetic risk factor for atopic dermatitis, alter the cutaneous microbiome thereby affecting keratinocyte host defense responses following skin barrier disruption

Atopic Dermatitis Susceptibility Variants in Filaggrin Hitchhike Hornerin Selective Sweep.

Human skin has evolved rapidly, leaving evolutionary signatures in the genome. The filaggrin (FLG) gene is widely studied for its skin-barrier function in humans. The extensive genetic variation in this gene, especially common loss-of-function (LoF) mutations, has been established as primary risk factors for atopic dermatitis. To investigate the evolution of this gene, we analyzed 2,504 human genomes and genotyped the copy number variation of filaggrin repeats within FLG in 126 individuals from diverse ancestral backgrounds. We were unable to replicate a recent study claiming that LoF of FLG is adaptive in northern latitudes with lower ultraviolet light exposure. Instead, we present multiple lines of evidence suggesting that FLG genetic variation, including LoF variants, have little or no effect on fitness in modern humans. Haplotype-level scrutinization of the locus revealed signatures of a recent selective sweep in Asia, which increased the allele frequency of a haplotype group (Huxian haplogroup) in Asian populations. Functionally, we found that the Huxian haplogroup carries dozens of functional variants in FLG and hornerin (HRNR) genes, including those that are associated with atopic dermatitis susceptibility, HRNR expression levels and microbiome diversity on the skin. Our results suggest that the target of the adaptive sweep is HRNR gene function, and the functional FLG variants that involve susceptibility to atopic dermatitis, seem to hitchhike the selective sweep on HRNR. Our study presents a novel case of a locus that harbors clinically relevant common genetic variation with complex evolutionary trajectories.

Association of atopic dermatitis with smoking: A systematic review and meta-analysis

Tobacco exposure might be a modifiable risk factor for atopic dermatitis (AD). We examine the associationbetween AD and exposure to tobacco smoke. We performed a systematic review and meta-analysis of observational studies (n=86) in MEDLINE, EMBASE, Scopus, and Cochrane Library (1823-2015). Quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). A meta-analysis was performed using random-effects models to estimate pooled odds ratios (OR). Subset analyses were performed for different ages (children, adult), regions, study designs (cross-sectional, longitudinal), study sizes (<5000, ≥5000), study quality (NOS score <6, ≥6), and amount of smoking (mild, extensive). A diagnosis of AD was associated with higher odds of active smoking (OR 1.87, 95% confidence interval 1.32-2.63) and exposure to passive smoke (OR 1.18, 95% confidence interval 1.01-1.38), but not maternal smoking during pregnancy (OR 1.06, 95% confidence interval 0.80-1.40). The association between active smoking and AD remained significant in children and adults, all continents studied, and study sizes, but all were cross-sectional designs and had NOS score 6 or greater. Passive smoke was associated with AD in children and adults, cross-sectional studies, South/Central American and African studies, study size less than 5000, and NOS score less than 6. AD severity and distribution were not assessed. Active and passive exposure to smoke are associated with increased AD prevalence.

Residential Risk Factors for Atopic Dermatitis in 3- to 6-Year Old Children: A Cross-Sectional Study in Shanghai, China

Background: Atopic dermatitis (AD) is common among pre-school children in Shanghai. This study aimed to identify the risk factors for childhood AD from the perspectives of home environment, demographics and parents-grandparents’ atopic disease. Methods: A cross-sectional study was conducted in Shanghai in April–June, 2010. Preschool children’s parents or guardians were invited to participate a questionnaire survey in six districts (two urban and four suburban/rural) and 6624 children were finally recruited (51.3% boys). AD diagnosis was based on the U.K. Working Party’s (UKWP) criteria. Adjusted odds ratios (AOR) with 95% confidence intervals (95% CI) were calculated by multiple logistic regression. Results: A total of 8.5% of children ever had AD. Around 10.2% of the mothers had lived in newly renovated/decorated homes (NRDH) during the prenatal period (one year before or during pregnancy) and 9.5% got new home furniture (NHF) during the same period. AD was more common in children when mothers had lived in NRDH homes during the prenatal period (AOR = 1.41; 95% CI 1.03–1.93), the current home had indoor mold (2.00, 1.48–2.70), parents-grandparents’ had atopic diseases (3.85, 3.05–4.87), the children had food allergy (3.40, 2.63–4.40) or children lived in urban area (1.52, 1.18–1.96). Associations between AD and NRDH, NHF and indoor molds were only significant in children without parents-grandparents’ atopic diseases. There was an interaction effect between parents-grandparents’ atopic diseases and NRDH (p < 0.05). Conclusions: Home renovation/ redecoration, new furniture and indoor mold, urban residency, heredity disposition and food allergy can be risk factors for childhood AD in Shanghai.

Neonatal risk factors of atopic dermatitis in Denmark - Results from a nationwide register-based study.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a multifactorial etiopathogenesis. Studies have suggested that several perinatal factors may influence the risk of AD in early childhood. We investigated possible neonatal risk factors such as jaundice, blue light phototherapy, birthweight, gestational age at birth, and season of birth on the risk of developing AD in the first 5years of life. Data were collected through Danish nationwide administrative registers. All newborn children between 1997 and 2007 (n=673,614) were included in the cohort. Incidence rate ratios (IRRs) were estimated with 95% confidence intervals (95% CIs) by multivariate Poisson regression analyses. We identified a total of 85,743 children with AD in the first 5years of life. The risk of AD was slightly increased in children with neonatal jaundice (IRR 1.13 [95% CI 1.06-1.21]). Preterm birth was inversely associated with the risk of AD (IRR 0.74, [95% CI 0.68-0.81]) as well as low birthweight (IRR 0.68, [95% CI 0.61-0.75]). Children born in fall and winter seasons had an increased risk of AD compared to spring and summer. No association between neonatal blue light therapy and the risk of AD was found. Low birthweight and preterm birth were inversely associated with AD, while neonatal jaundice and cold seasons of birth were associated with an increased risk of AD.