This cross-sectional study examines whether atopic dermatitis is associated with symptoms of learning or memory difficulties in US children.
Key Points
Question
Is atopic dermatitis (AD) associated with symptoms of cognitive impairment in children?
Findings
In this cross-sectional study that used 2021 US National Health Interview Survey data, a weighted sample of 69 732 807 children with AD were more likely to experience learning and memory difficulties than those without AD. However, these associations were primarily limited to children with neurodevelopmental comorbidities, such as attention-deficit/hyperactivity disorder or learning disabilities, and were not observed among children without comorbid neurodevelopmental disorders.
Meaning
The findings of this study suggest that evaluation for cognitive impairment in children with AD should be prioritized among those with comorbid neurodevelopmental disorders.
Abstract
Importance
Previous studies suggest that atopic dermatitis (AD) is associated with cognitive impairment in children, but these studies have relied primarily on neurodevelopmental diagnoses (rather than symptoms) as proxy measures of cognitive function. It remains unknown if certain subpopulations of children with AD are at greater risk of cognitive impairment.
Objective
To examine the association of AD with symptoms of cognitive impairment (difficulty in learning or memory) among US children and whether this association varies according to the presence or absence of neurodevelopmental comorbidities (attention-deficit/hyperactivity disorder [ADHD], developmental delay, or learning disability).
Design, Setting, and Participants
This cross-sectional study used 2021 data from the US National Health Interview Survey collected on children aged 17 years or younger without intellectual disability or autism. The presence of AD was based on a parent or adult caregiver’s report indicating either a current diagnosis of AD or a previous medical confirmation of AD by a health care professional.
Main Outcomes and Measures
Difficulty with learning or memory as reported by the child’s caregiver.
Results
Among the weighted total of 69 732 807 participants, 9 223 013 (13.2%) had AD. Compared with children without AD, children with AD were more likely to experience difficulties with learning (10.8% [95% CI, 7.8%-15.8%] vs 5.9% [95% CI, 5.1%-6.9%]; P < .001) and difficulties with memory (11.1% [95% CI, 8.0%-15.9%] vs 5.8% [95% CI, 4.9%-6.9%]; P < .001). In multivariable logistic regression models adjusted for sociodemographic factors, asthma, food allergies, and seasonal allergies or hay fever, AD was associated with increased odds of difficulties in learning (adjusted odds ratio [AOR], 1.77; 95% CI, 1.28-2.45) and memory (AOR, 1.69; 95% CI, 1.19-2.41). In analyses stratified by neurodevelopmental comorbidities, AD was associated with 2- to 3-fold greater odds of memory difficulties among children with any neurodevelopmental disorder (AOR, 2.26; 95% CI, 1.43-3.57), including ADHD (AOR, 2.90; 95% CI, 1.60-5.24) or learning disabilities (AOR, 2.04; 95% CI, 1.04-4.00). However, AD was not associated with learning or memory difficulties among children without neurodevelopmental conditions.
Conclusions and Relevance
Results of this cross-sectional study suggest that pediatric AD was generally associated with greater odds of reported difficulties in learning and memory. However, this association was primarily limited to children with neurodevelopmental comorbidities, such as ADHD or learning disabilities. These findings may improve the risk stratification of children with AD for cognitive impairments and suggest that evaluation for cognitive difficulties should be prioritized among children with AD and neurodevelopmental disorders.
Introduction
Atopic dermatitis (AD) in children has been linked with sleep disturbances, inattention, and learning disabilities.1,2,3 Cognitive dysfunction has been reported among children with AD,4,5 but whether specific subgroups are more susceptible is unknown. Additionally, previous studies have often relied on caregiver-reported diagnoses of attention-deficit/hyperactivity disorder (ADHD) or developmental delay as proxies of cognitive dysfunction rather than examining symptoms of cognitive impairment. Thus, we investigated the association between AD and learning or memory difficulties and whether this association varies according to the presence or absence of comorbid neurodevelopmental conditions (ie, ADHD, developmental delay, or learning disability).
Methods
We used data from the 2021 National Health Interview Survey (NHIS), which captures a representative sample of US households. The survey randomly selects 1 child per surveyed household for whom a parent or adult caregiver provides information.6The study was considered exempt by the Johns Hopkins Institutional Review Board due to the use of publicly available deidentified data. This cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
We included all children aged 17 years or younger without intellectual disability or autism. Atopic dermatitis was defined by answering yes to either of the following questions: “Does the child get an itchy rash due to eczema or atopic dermatitis?” or “Have you ever been told by a doctor or other health professional that the child had eczema or atopic dermatitis?” Learning disability, developmental delay, and ADHD were also determined by direct questions. Learning and memory difficulties were assessed using the following question: “Compared with children of the same age, does the child have difficulty learning [or difficulty remembering] things?”
Statistical Analysis
Learning and memory difficulties were analyzed as dichotomous outcomes (any difficulty vs no difficulty). Logistic regression was performed to compare the odds of learning or memory difficulties between children with and without AD. Analyses were stratified by neurodevelopmental comorbidities and adjusted for sex, age, race and ethnicity, region, ratio of household income to poverty threshold, highest educational attainment of adult in household, insurance status, and general health. As disparities by race, ethnicity, and socioeconomic factors have been identified in the diagnosis and treatment of AD and neurodevelopmental disorders,7,8 these data were included as covariates. Race was self-reported as Asian, American Indian or Alaska Native, Black or African American, White, or other (including Native Hawaiian or Other Pacific Islander, multiracial, or declined to answer). Ethnicity was self-reported as Hispanic or not Hispanic. Considering the co-occurrence of AD with other atopic disorders that may also affect cognition,9 we additionally adjusted for asthma, seasonal allergies, and food allergies. To account for NHIS sampling design, weight adjustments were used to obtain population estimates. Sensitivity analyses limited to children aged older than 5 years were also conducted. Data were analyzed in Stata, version 17 (StataCorp, LLC) and significance was determined by χ2 test for categorical variables and t test for continuous variables; a 2-sided P < .05 was considered statistically significant.
Results
The 7957 children sampled represented a weighted total of 69 732 807 children. Within the weight-adjusted population, 9 223 013 children (13.2%) had AD (Table 1). Children with AD were more likely to be of Black or non-Hispanic race and ethnicity, have poorer health, and have other atopy. Compared with children without AD, all 3 neurodevelopmental conditions were more common in the children with AD: ADHD, 11.3% (95% CI, 9.1%-14.0%) vs 7.2% (95% CI, 6.6%-8.0%); developmental delay, 7.8% (95% CI, 6.1%-10.1%) vs 4.1% (95% CI, 3.5%-4.7%); and learning disability, 7.5% (95% CI, 5.7%-9.7%) vs 4.5% (95% CI, 4.0%-5.2%).
Table 1. Characteristics of Study Participants by AD Status.
| Characteristic | Weighted sample, % (95% CI) | P value | ||
|---|---|---|---|---|
| Total (N = 69 732 807) | Children with AD (n = 9 223 013) | Children without AD (n = 60 509 794) | ||
| Sex | ||||
| Male | 50.3 (48.9-51.6) | 49.2 (45.7-52.7) | 50.4 (49.0-51.9) | .69 |
| Female | 49.7 (48.4-51.1) | 50.8 (47.3-54.3) | 49.6 (48.1-51.0) | |
| Age, y, mean (SD) | 8.6 (5.2) | 8.4 (5.1) | 8.7 (5.2) | .11 |
| Race | ||||
| Asian | 4.8 (4.2-5.4) | 4.8 (3.7-6.2) | 4.8 (4.2-5.4) | <.001 |
| Black or African American | 12.1 (11.0-13.4) | 15.3 (12.6-18.4) | 11.7 (10.4-13.0) | |
| White | 77.0 (73.0-81.1) | 71.1 (64.1-78.4) | 77.9 (73.6-82.2) | |
| Othera | 6.1 (5.0-7.6) | 8.9 (6.4-12.5) | 5.7 (4.6-7.3) | |
| Ethnicity | ||||
| Hispanic | 25.7 (23.8-27.7) | 24.0 (20.9-27.4) | 26.0 (23.9-28.1) | <.001 |
| Non-Hispanic | 74.3 (69.5-79.7) | 76.0 (66.0-88.1) | 74.0 (68.9-79.8) | |
| Highest educational attainment of adult in household | ||||
| Did not graduate high school | 5.5 (4.6-6.6) | 3.2 (1.7-6.2) | 5.8 (4.9-7.0) | .05 |
| High school graduate or GED | 18.4 (17.0-20.0) | 17.7 (14.3-22.0) | 18.5 (17.0-20.2) | |
| Some college | 14.2 (13.3-15.1) | 14.6 (12.3-17.2) | 14.1 (13.2-15.1) | |
| Associate’s degree | 13.3 (12.0-14.7) | 12.7 (9.9-16.2) | 13.4 (12.0-15.0) | |
| Bachelor’s degree | 25.2 (24.0-26.5) | 27.3 (24.3-30.5) | 24.9 (23.6-26.3) | |
| Graduate or professional degree | 23.4 (21.7-25.2) | 24.6 (20.6-29.2) | 23.2 (21.4-25.1) | |
| Ratio of household income to poverty thresholdb | ||||
| 0-0.99 | 16.3 (14.3-18.7) | 15.9 (11.2-22.5) | 16.4 (14.2-18.9) | .84 |
| 1.00-1.99 | 22.9 (20.4-25.6) | 22.9 (17.0-30.8) | 22.9 (20.2-25.8) | |
| 2.00-2.99 | 15.7 (14.3-17.2) | 13.9 (11.0-17.6) | 16.0 (14.5-17.6) | |
| 3.00-3.99 | 13.2 (12.0-14.5) | 13.7 (10.7-17.5) | 13.1 (11.8-13.9) | |
| 4.00-4.99 | 9.4 (8.4-10.6) | 8.9 (6.7-11.9) | 9.5 (8.4-10.8) | |
| ≥5.00 | 22.5 (21.2-23.8) | 24.6 (21.8-27.6) | 22.1 (20.8-23.5) | |
| Region | ||||
| Northeast | 15.6 (14.2-17.0) | 12.4 (10.2-15.1) | 16.0 (14.6-17.6) | .07 |
| Midwest | 21.1 (19.5-22.8) | 21.8 (18.6-25.4) | 21.0 (19.4-22.7) | |
| South | 39.2 (37.2-41.2) | 39.7 (35.8-43.7) | 39.1 (37.0-41.1) | |
| West | 24.2 (22.2-26.2) | 26.1 (22.6-29.9) | 23.9 (22.0-25.9) | |
| Has health insurance | 96.2 (95.6-96.7) | 97.5 (95.6-98.6) | 96.0 (95.3-96.5) | .23 |
| General health status | ||||
| Excellent | 67.6 (66.3-68.9) | 55.0 (51.5-58.5) | 69.6 (68.1-70.9) | <.001 |
| Very good | 21.4 (20.3-22.5) | 26.1 (23.0-29.5) | 20.7 (19.6-21.8) | |
| Good | 9.2 (8.4-10.1) | 14.4 (12.0-17.2) | 8.4 (7.6-9.4) | |
| Fair | 1.6 (1.3-2.0) | 4.3 (2.8-6.5) | 1.2 (0.9-1.6) | |
| Poor | 0.2 (0.1-0.3) | 0.3 (0.1-0.7) | 0.1 (0.1-0.3) | |
| History of asthma | 9.9 (9.1-10.6) | 20.5 (17.9-23.4) | 8.2 (7.5-9.0) | <.001 |
| History of seasonal allergies or hay fever | 31.8 (30.6-33.2) | 54.3 (50.7-57.7) | 28.4 (27.1-29.8) | <.001 |
| History of food allergies | 7.8 (7.1-8.5) | 20.6 (17.8-23.6) | 5.8 (5.2-6.5) | <.001 |
| History of ADHD | 7.8 (7.1-8.5) | 11.3 (9.1-14.0) | 7.2 (6.6-8.0) | <.001 |
| History of developmental delay | 4.6 (4.0-5.1) | 7.8 (6.1-10.1) | 4.1 (3.5-4.7) | <.001 |
| History of learning disability | 4.9 (4.4-5.6) | 7.5 (5.7-9.7) | 4.5 (4.0-5.2) | .01 |
| Difficulty learning | ||||
| No difficulty | 93.4 (92.7-94.0) | 89.2 (86.5-91.4) | 94.0 (93.3-94.7) | <.001 |
| Some difficulty | 5.7 (5.1-6.3) | 8.6 (6.7-11.0) | 5.2 (4.6-5.9) | |
| A lot of difficulty | 0.9 (0.6-1.2) | 2.1 (1.1-4.0) | 0.7 (0.5-0.9) | |
| Cannot do at all | 0.0 (0.0-0.1) | 0.1 (0.0-0.8) | 0.0 (0.0-0.1) | |
| Difficulty remembering | ||||
| No difficulty | 93.5 (92.7-94.2) | 88.8 (85.9-91.2) | 94.2 (93.4-95.0) | <.001 |
| Some difficulty | 5.7 (5.0-6.5) | 9.0 (6.9-11.7) | 5.2 (4.5-6.0) | |
| A lot of difficulty | 0.8 (0.5-1.1) | 1.9 (1.1-3.4) | 0.6 (0.4-0.9) | |
| Cannot do at all | 0.0 (0.0-0.1) | 0.2 (0.0-0.8) | 0.0 (0.0-0.0) | |
Abbreviations: AD, atopic dermatitis; ADHD, attention-deficit/hyperactivity disorder; GED, General Educational Development.
Includes American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, White, or other (including multiracial or declined to answer).
Denotes the relationship between the reported household income and the poverty threshold. Established by the US Census Bureau, the poverty threshold is the minimum level of income required to meet basic needs. The following categories are used to interpret the values: 0-0.99: below the poverty threshold; 1.00-1.99: near to moderately above the poverty threshold; 2.00 and above: well above the poverty threshold.
Compared with children without AD, children with AD were more likely to experience difficulties with learning (10.8% [95% CI, 7.8%-15.8%] vs 5.9% [95% CI, 5.1%-6.9%]; P < .001) and difficulties with memory (11.1% [95% CI, 8.0%-15.9%] vs 5.8% [95% CI, 4.9%-6.9%]; P < .001) (Table 1). Only 58.7% (95% CI, 49.9%-66.9%) of children with AD and any neurodevelopmental comorbidity reported no learning difficulty compared with 96.4% (95% CI, 94.4%-97.7%) of children with AD but without neurodevelopmental comorbidities (Table 2). Similarly, 60.4% (95% CI, 51.5%-68.6%) of children with AD and any neurodevelopmental comorbidity reported no memory difficulties compared with 96.3% (95% CI, 94.1%-97.7%) of children with AD but without neurodevelopmental comorbidities.
Table 2. Prevalence of Symptoms of Cognitive Impairment by AD Status, Stratified by the Presence or Absence of Neurodevelopmental Comorbidity.
| Outcome | Weighted sample, % (95% CI) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No neurodevelopmental comorbidities | Any neurodevelopmental comorbidities | ADHD | Developmental delay | Learning disabilities | ||||||
| AD | No AD | AD | No AD | AD | No AD | AD | No AD | AD | No AD | |
| Difficulty learning | ||||||||||
| No difficulty | 96.4 (94.4-97.7) | 97.7 (97.2-98.2) | 58.7 (49.9-66.9) | 67.4 (63.4-71.2) | 60.6 (48.8-71.2) | 73.5 (68.7-77.8) | 54.5 (40.4-68.0) | 58.6 (51.1-65.8) | 38.2 (26.6-51.3) | 36.4 (30.0-43.6) |
| Some difficulty | 3.5 (2.2-5.5) | 2.2 (1.7-2.7) | 30.3 (33.0-38.8) | 26.9 (23.3-30.9) | 27.8 (18.9-39.0) | 21.4 (17.4-26.1) | 29.5 (19.0-42.7) | 31.9 (25.0-39.6) | 37.6 (25.5-51.5) | 54.0 (46.9-60.8) |
| A lot of difficulty | 0.1 (0.0-0.7) | 0.1 (0.1-0.2) | 10.5 (5.4-19.5) | 5.1 (3.6-7.1) | 11.6 (4.7-25.9) | 5.1 (3.3-7.8) | 16.0 (6.7-33.6) | 7.8 (4.7-12.5) | 22.7 (11.2-40.7) | 9.1 (6.1-13.5) |
| Cannot do at all | 0 | 0 | 0.6 (0.1-3.9) | 0.2 (0.0-0.8) | 0 | 0 | 0 | 0.5 (0.1-2.1) | 1.4 (0.2-9.5) | 0.5 (0.1-2.0) |
| Difficulty remembering | ||||||||||
| No difficulty | 96.3 (94.1-97.7) | 96.8 (96.1-97.4) | 60.4 (51.5-68.6) | 77.7 (74.0-81.1) | 52.8 (41.2-64.1) | 76.0 (71.2-80.2) | 61.6 (44.8-76.0) | 70.7 (62.6-77.7) | 51.8 (38.4-64.9) | 67.9 (60.9-74.1) |
| Some difficulty | 3.4 (2.0-5.6) | 3.0 (2.5-3.8) | 30.3 (22.6-39.3) | 18.9 (15.8-22.5) | 38.9 (28.1-50.9) | 20.7 (16.9-25.2) | 25.1 (12.7-43.5) | 22.9 (16.7-30.6) | 35.3 (22.7-50.3) | 26.5 (20.6-33.3) |
| A lot of difficulty | 0.3 (0.1-1.2) | 0.1 (0.1-0.3) | 8.2 (4.4-14.7) | 3.4 (2.1-5.4) | 7.6 (3.4-16.0) | 3.3 (1.8-5.9) | 12.7 (5.4-27.1) | 6.3 (3.3-11.9) | 11.5 (5.3-23.0) | 5.7 (3.1-10.1) |
| Cannot do at all | 0 | 0 | 0.9 (0.2-3.9) | 0 | 0.4 (0.1-2.6) | 0 | 0.6 (0.1-4.5) | 0 | 1.4 (0.2-9.6) | 0 |
Abbreviations: AD, atopic dermatitis; ADHD, attention-deficit/hyperactivity disorder.
In adjusted analyses, AD was associated with increased odds of difficulties in learning (adjusted odds ratio [AOR], 1.77; 95% CI, 1.28-2.45) and memory (AOR, 1.69; 95% CI, 1.19-2.41) (Figure). Older age was associated with slightly increased odds of difficulties in learning (AOR, 1.07; 95% CI, 1.05-1.10) and memory (AOR, 1.11; 95% CI, 1.08-1.13). Female sex was associated with lower odds of learning difficulties (AOR, 0.76; 95% CI, 0.60-0.96).
Figure. Adjusted Odds Ratios (AORs) of Symptoms of Cognitive Impairment Among Children With Atopic Dermatitis (AD) Relative to Children Without AD.
All models were adjusted for sex, age, race and ethnicity, highest educational attainment of adult in household, ratio of household income to poverty threshold, geographic region, insurance status, general health status, history of asthma, history of food allergies, and history of seasonal allergies or hay fever. ADHD indicates attention-deficit/hyperactivity disorder.
aComorbid neurodevelopmental conditions include ADHD, developmental delay, and learning disability.
In stratified analyses, AD was associated with greater odds of memory difficulties among children with neurodevelopmental disorders (AOR, 2.26; 95% CI, 1.43-3.57), including children with ADHD (AOR, 2.90; 95% CI, 1.60-5.24) or learning disabilities (AOR, 2.04; 95% CI, 1.04-4.00). Atopic dermatitis was also associated with 52% greater odds of learning difficulties among children with neurodevelopmental disorders (AOR, 1.52; 95% CI, 1.00-2.32), particularly ADHD (AOR, 1.78; 95% CI, 0.97-3.26), albeit this finding was not statistically significant (Figure). Among children without neurodevelopmental comorbidities, there were no significant associations between AD and memory or learning difficulties. A statistically significant interaction between AD and neurodevelopmental comorbidity was observed for memory difficulties (P for interaction = .02) but not for learning difficulties (P for interaction = .90). As ADHD and learning disabilities are rarely diagnosed before the child is of school age, we repeated analyses among children aged older than 5 years; findings were similar.
Discussion
The findings of this cross-sectional, population-based study suggest that US children with AD have higher odds of having learning and memory difficulties than children without AD, but this association was primarily limited to those with known ADHD or learning disability. In contrast, AD was not associated with learning or memory difficulties among children without an existing neurodevelopmental disorder.
Our findings align with those of other studies reporting cognitive impairments, including worse memory and lower IQ, in children with AD.5,10 Our study also expands upon previous US population–based pediatric studies of AD and cognition by separating symptoms of cognitive impairment from diagnoses of neurodevelopmental conditions that serve as proxies for cognitive dysfunction. Our finding that cognitive impairment associated with AD was primarily limited to children with concomitant ADHD or learning disabilities suggests that these are the subgroups of children with AD who are at highest risk of cognitive impairments. Additionally, our findings suggest that the combination of AD and neurodevelopmental disorders may impair memory more than either alone. While the mechanisms by which AD may interact with neurodevelopmental disorders to impair cognition are unknown, one possibility is that AD-related sleep disturbances may be more likely to negatively impact functions, such as memory in children with ADHD or learning disability, than in children without neurodevelopmental conditions.11
Our results also suggest that memory and learning difficulties related to AD may vary by neurodevelopmental condition. Among children with ADHD, AD was associated with nearly 3-fold greater odds of memory difficulties but was not associated with learning difficulties. In contrast, among children with learning disabilities, AD was associated with twice the odds of memory difficulties but half the odds of learning difficulties (Figure). Several possible explanations for these latter findings may be posited. One is that children with concomitant learning disabilities and AD are more likely to receive appropriate interventions, perhaps due to greater health care use or awareness by caregivers or clinicians, thus leading to the relatively lower odds of learning difficulties reported. Another possibility is that AD affects different areas of cognition to varying degrees, with perhaps a greater impact on memory than on learning. For example, sleep disturbances from AD may contribute to greater difficulties with memory in this context.12,13
Strengths and Limitations
Study strengths include the population-based nature and data adjustment for multiple confounders. However, we were limited by the cross-sectional design and reliance on caregiver reports. Although caregiver-reported AD data are widely used to study AD epidemiology in the US and have been validated,5,14,15 caregiver-perceived cognitive difficulties may be biased. Finally, we were unable to examine factors, such as AD severity, age at AD diagnosis, and sleep, which were not collected in the NHIS data.
Conclusions
The results of this population-based, cross-sectional study suggest that AD is associated with higher odds of symptoms of cognitive impairment primarily among children with neurodevelopmental disorders, such as ADHD or learning disability. These findings may improve the risk stratification of children with AD for cognitive impairment and suggest that evaluation for cognitive impairment should be prioritized among children with AD and comorbid ADHD or learning disability.
Data Sharing Statement
References
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Supplementary Materials
Data Sharing Statement
