Is atopy in early childhood a risk factor for ADHD and ASD? A longitudinal study
Introduction
Atopic diseases of childhood consist of atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and asthma, and have been regarded as the most common chronic disorders of childhood [2], [34], [35], [37]. The prevalence rates of atopic diseases rose gradually over the past several decades, and have been reaching epidemic proportions in both the developed and developing world [1], [17], [19], [36]. The International Study of Asthma and Allergies in Childhood reported that from the 1990s to early 2000, the prevalence of asthma, allergic rhinitis, and atopic dermatitis rose significantly in Australia, from 4.4%, 3.7%, and 10.1% to 5.1%, 4.5%, and 13.8%, respectively, among children [31]. In the United States, the prevalence of childhood asthma doubled from approximately 3% in early 1980 to 7.5% in 1995 [40]. Atopic diathesis or atopic disease has become an important public health problem among children [1], [17], [19], [36].
Similar to the increased prevalence of atopy worldwide over the last few decades, the prevalence rates of childhood neurodevelopmental disorders, including attention-deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD), have risen gradually and simultaneously [4], [9]. The 1997–2008 National Health Interview Surveys in the United States reported that the prevalence of ADHD and ASD increased, respectively, from 5.69% to 7.57% and 0.19% to 0.74% over 12 years [9]. A Danish birth cohort study followed all children born from 1990 through 1999 to the end of 2004 and reported that the cumulative incidence of ADHD and ASD across specific birth years showed statistically significant increases [4]. The temporal concordance of the increased prevalence of atopy, ADHD, and ASD has inspired many scientists in recent years to investigate the possible etiological association between these 3 clinically distinct diseases.
Previous findings regarding the association among atopy, ASD, and ADHD have been inconsistent [6], [7], [21], [27], [32], [42]. Biederman et al. failed to validate the association between asthma and ADHD among 140 ADHD children aged 6–17 years and controls [7]. Bakkaloglu et al. found that young autistic children (n = 30) did not present more allergic features, based on history, skin tests, and serum immunoglobulin (Ig)-E levels, than the normal controls (n = 39) [6]. However, several larger sample-size studies supported the relationship of atopy with ADHD and ASD [27], [32], [42]. The 2007 National Survey of Children's Health in the United States, composed of 92,642 children aged 0 to 17 years, demonstrated that the odds of having ADHD (odds ratio [OR]: 1.87, 95%CI: 1.54–2.27) and ASD (OR: 3.04, 95%CI: 2.13–4.34) were significantly increased in children with atopic dermatitis compared with the control subjects [42]. Mogensen et al. found that children with asthma at age 8–9 years had an almost twofold increased risk (OR: 1.88, 95% CI: 1.18–3.00) of having one or more symptoms of hyperactivity/impulsivity, and a more than twofold increased risk (OR: 2.73, 95% CI: 1.49–5.00) of having 3 or more symptoms of hyperactivity/impulsivity at age 13–14 years [27]. However, the limitations in those previous studies included that the diagnoses of ADHD and ASD were given by parental reports or questionnaires, and not by board certificated psychiatrists, and that a cross-sectional study design, and not a longitudinal follow-up design was used.
In our study, utilizing the Taiwan National Health Insurance Research Database (NHIRD) with a large sample size and a longitudinal follow-up study design, we followed newborns between 1997 and 2000 to the end of 2010, and investigated the association between atopic diathesis in early childhood (before the age of 3) and the risk of ADHD and ASD in later life. We hypothesized that subjects who had any atopic disease in early childhood had an increased risk of developing ADHD and ASD in later life.
Section snippets
Data source
The National Health Insurance (NHI) program was implemented in 1995 and covers up to 99% of the 23,000,000 residents of Taiwan (http://www.nhi.gov.tw/). The NHIRD was audited and released by the National Health Research Institute. Comprehensive information on insured subjects, such as demographic data, dates of clinical visits, and disease diagnoses, is included in the database. To guarantee privacy, all subjects included in the NHIRD are anonymous. The diagnostic codes used were based on the
Results
In all, 14,812 atopic subjects (atopic cohort) with a mean 1.33 ± 0.86 years of diagnosis of any atopic disease and 6944 non-atopic subjects (non-atopic cohort) with no lifetime atopic disease, born between 1997 and 2000, were enrolled in our study, and followed to the onset of events (ASD or ADHD), the study end (December 31, 2010), or the death. During the follow-up, 557 (2.6%) subjects died and withdrew from NHIRD. The atopic cohort was more male-predominant than the non-atopic cohort (55.6%
Discussion
Our results supported the study hypotheses that atopic diathesis in early childhood (before the age of 3) increased the risk of developing ADHD and ASD in later life, and that there was a dose-dependent relationship between more atopic comorbidities with a greater likelihood of ADHD and ASD.
Atopy and ADHD
The comorbid or causal role of atopy and atopic immunological responses in the development of ADHD has been debated for a long time [7], [12], [13], [27], [32], [42]. In the late 1980s, Marshall et al. proposed a potential neuro-immunological model of ADHD, and hypothesized that atopic reactions engendering cholinergic/adrenergic activity imbalances in the central nervous system led to ADHD symptoms in some children [26]. As mentioned in the Introduction, several small sample-size studies in
Conflict of Interest
No conflict of interest.
Financial disclosure
All authors have no financial relationships relevant to this article to disclose.
Acknowledgment
The study was supported by grant from Taipei Veterans General Hospital (V103E10-001).
We thanks Dr MHC, Dr TPS, and Dr YMB, who designed the study, and wrote the protocol and manuscripts, Dr YMB, Dr TPS, Dr YSC, Dr JWH, Dr KLH, and TLP who assisted with the preparation and proof-reading of the manuscript, and Dr YMB, Dr TJC, and Ms WHC, who provided advice on statistical analysis.
We thank Mr I-Fan Hu's friendship and support.
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