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CME / ABIM MOC / CE

Are Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Significantly Linked to Childhood Allergies?

  • Authors: News Author: Lorraine L. Janeczko, MPH; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 8/5/2022
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 8/5/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for pediatricians, internists, family medicine and primary care clinicians, pharmacists, nurses, neurologists, allergists and clinical immunologists, physician assistants, adolescent medicine clinicians, and other members of the health care team for patients with childhood allergies who may be at risk for attention-deficit/hyperactivity disorder and autism spectrum disorder.

The goal of this activity is for learners to be better able to describe the association of allergic disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder in a large cohort of pediatric patients (0-18 years), based on a retrospective study using the pediatric database (International Classification of Diseases, 9th revision, Clinical Modification codes) of Clalit Health Services during 2000 to 2018.

Upon completion of this activity, participants will:

  • Assess the association of allergic disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder in a large cohort of pediatric patients, based on a retrospective database study
  • Evaluate the clinical implications of the association of allergic disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder in a large cohort of pediatric patients, based on a retrospective database study
  • Outline implications for the healthcare team


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News Author

  • Lorraine L. Janeczko, MPH

    Freelance writer, Medscape

    Disclosures

    Lorraine L. Janeczko, MPH, has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Are Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Significantly Linked to Childhood Allergies?

Authors: News Author: Lorraine L. Janeczko, MPH; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME / ABIM MOC / CE Released: 8/5/2022

Valid for credit through: 8/5/2023, 11:59 PM EST

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Clinical Context

Allergic disorders including atopic dermatitis and other dermatological diseases, rhino-conjunctivitis, asthma, food, and drug allergies are common in children, with increasing prevalence especially in highly developed countries. These may cause physical discomfort and mental and behavioral problems.

Attention-deficit/hyperactivity disorder (ADHD), characterized by inattention and hyperactivity, affects 9% to 12% of the US population. ASD is characterized by deficits in social interaction and language communication, with US prevalence of approximately 2.47%.

Study Synopsis and Perspective

Young children with allergies may be more likely to develop ADHD and autism spectrum disorder (ASD) by the time they are 18 years old, according to a large retrospective study.[1]

"[O]ur study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD," Shay Nemet, MD, from the Kaplan Medical Center in Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. "The risk of those children to develop ASD was less significant."

The researchers analyzed data from 117,022 consecutive children diagnosed with at least 1 allergic disorder (asthma, conjunctivitis, rhinitis, drug, food, or skin allergy) and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with 1 or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio [OR], 2.45; 95% confidence interval [CI], 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.

Allergy Correlation With ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children's Mercy Kansas City, in Missouri, told Medscape Medical News that children and adults with neurodevelopmental differences are also more likely to have other health problems.

"Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood," he added.

"Studies like this can't be accomplished without large healthcare databases, but this approach has drawbacks, too," Dr Nadler said in an email. "Without more information about these patients' co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations."

Dr Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, sex, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

"It is important to remember not to interpret these study results as causal," he added.

Desha M. Jordan, MD, an assistant professor of pediatrics at UPMC Children's Hospital of Pittsburgh, Pennsylvania, called the study "an interesting new area that has been speculated about for some time," and "one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions."

More Questions for Future Studies

Healthcare providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study's retrospective design and the possibility of recall bias were limitations, said Dr Jordan in an email. She also was not involved in the study.

"For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child's past, while the family of a child without these conditions may not have recalled allergic symptoms as important," she explained.

Another question that arises is whether some patients were treated and managed well while others were not, and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

"Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?

"While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research," Dr Jordan said. "More studies in this area are necessary to confirm the findings of this paper."

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr Nadler, and Dr Jordan have disclosed no relevant financial relationships.

Pediatr Allergy Immunol. Published online June 17, 2022.

Study Highlights

  • The sample for this retrospective study, identified from International Classification of Diseases, 9th revision, Clinical Modification, codes in a pediatric database, included 117,022 consecutive children diagnosed by specialists as having at least 1 allergic disorder (asthma, rhinitis, conjunctivitis, skin, food, or drug allergy) during 2000 to 2018, and 116,968 children without allergic disorder.
  • Mean age of allergic diagnosis was 4.5±4.3 years; mean follow-up was 11±6 years.
  • During follow-up, 14% of patients were diagnosed with ADHD, 0.99% with ASD, and 0.34% with both.
  • Significantly more allergic vs nonallergic patients were diagnosed with ADHD (19.3% vs 8.9%;), ASD (1.1% vs 0.9%), or both (0.4% vs 0.3%; all P<.0001).
  • Mean age at first neurologic disorder diagnosis was 8.5±3.4 years for ADHD, 5.1±3.5 years for ASD, and 5.0±2.9 years for both, and was similar in allergic and nonallergic patients.
  • For boys and girls, the presence of allergic disorders in early childhood was associated with significantly increased risk for development of ADHD (OR, 2.45; 95% CI, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both (OR, 1.5; 95% CI, 1.35-1.79; all P<.0001).
  • Children diagnosed with rhinitis (OR, 0.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were most likely to develop ADHD, but all allergic disorders were significantly associated with increased risk for ADHD and ASD, except for drug allergy, which almost reached statistical significance.
  • In multivariable analysis adjusted for age at study entry, number of yearly visits, and sex, children with more than 1 allergic condition (~40% of allergic patients) had much higher risk, and risk of allergic children for development of ADHD and ADHD + ASD, but not ASD alone, remained significantly higher.
  • OR for development of ASD alone was significant for boys (OR, 1.13; 95% CI 1.03-1.24), but not for girls.
  • The investigators concluded that their study provided strong evidence for the association between allergic disorders in early childhood and subsequent development of ADHD, and to a lesser extent ASD.
  • The dose-dependent relationship, with increased ADHD/ASD risk in children with several allergic conditions, further supports the link between allergic disorders and ADHD/ASD.
  • Clinicians caring for children with allergic conditions may help psychologists identify developmental and behavioral concerns early in childhood.
  • Awareness of the association between allergic disorders and development of ADHD/ASD facilitates early diagnosis and better treatment of allergic children with neurobehavioral symptoms.
  • Early and effective treatment of allergic disorders, including sleep disorders, stress, and physical discomforts, may reduce the development of ADHD, ASD and other neurobehavioral disorders, although this is unproven.
  • Possible mechanisms for the association between allergic disorders and ADHD/ASD may include shared genetic and environmental factors and/or mast cell activation and high levels of inflammatory cytokines in patients with allergic disorders causing neuroimmune microglial and mTOR activation, brain inflammation, and neurobehavioral disorders.
  • In addition, stress, fear, and sleep disturbances, and/or use of antihistamines passing the blood-brain barrier in allergic children, may contribute to ADHD/ASD development.
  • Study limitations include recall bias, retrospective design precluding causal inferences, and those inherent in database analysis, including lack of data about comorbid medical and behavioral conditions that could be contributing to the observed associations.
  • Unanswered questions meriting further research include whether treatment disparity for allergies affected risk for development or severity of ADHD or ASD.

Clinical Implications

  • Allergic disorders in early childhood are associated with subsequent development of ADHD and, to a lesser extent, ASD.
  • Clinicians caring for children with allergic conditions may help psychologists identify developmental and behavioral concerns early in childhood.
  • Implications for the Health Care Team: The healthcare team should advocate for early, effective treatment of allergic disorders to potentially reduce ADHD/ASD development.

 

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