Article 1: Migraine Risk in Children and Adolescents with Autism Spectrum Disorder
Jânice Roberta de Paula
2025-12-28
1 Introduction
Autism Spectrum Disorder (ASD) has been associated with a range of comorbidities, including neurological conditions such as migraine. Previous studies suggest that children and adolescents with ASD have a higher risk of developing migraine compared to healthy controls. The present study aims to analyze the prevalence of migraine and to assess the risk associated with ASD using Cox proportional hazards regression and sensitivity analyses
2 Methods
Study population: Children and adolescents with a confirmed diagnosis of Autism Spectrum Disorder (ASD) were included and matched with controls by age and sex. Participants were followed from study enrollment until the occurrence of the outcome or the end of the observation period.
Primary outcome: Incidence of migraine, assessed in both groups.
Statistical analyses:
Prevalence comparison (%) between the ASD and control groups.
Cox proportional hazards models: estimation of the relative risk (Hazard Ratio, HR) of developing migraine, with 95% confidence intervals (95% CI).
Sensitivity analyses: exclusion of the first year of follow-up and exclusion of medical and psychiatric comorbidities to assess the robustness of the findings.
Statistical analyses: 1. Prevalence comparison (%) between the ASD and control groups. 2. Cox proportional hazards models: estimation of the relative risk (Hazard Ratio, HR) of developing migraine, with 95% confidence intervals (95% CI). 3. Sensitivity analyses: exclusion of the first year of follow-up and exclusion of medical and psychiatric comorbidities to assess the robustness of the findings.
3 Results
Table 1 - Prevalence of Migraine
| Table 1 – Prevalence of migraine | |||
| Patients with ASD and controls | |||
| Variable | ASD (n, %) | Controls (n, %) | p-value |
|---|---|---|---|
| (n = 18,035) | (n = 18,035) | ||
| Age at enrollment (years, SD, n, %) | 8.68 (4.49) | 8.70 (4.49) | 0.627 |
| Sex (%) | 1.000 | ||
| Male | 14883 (82.5) | 14883 (82.5) | |
| Female | 3152 (17.5) | 3152 (17.5) | |
| Distribution of diagnoses (n, %) | |||
| Autistic disorder (ICD-9-CM code: 299.0) | 14,150 (78.5) | ||
| Other specified or unspecified pervasive developmental disorders (ICD-9-CM codes: 299.8, 299.9) | 3839 (21.3) | ||
| Childhood disintegrative disorder (ICD-9-CM code: 299.1) | 46 (0.2) | ||
| Incidence of migraine (n, %) | 74 (0.4) | 20 (0.1) | <0.001 |
| Age at migraine diagnosis (years, SD) | 13.35 (4.66) | 23.63 (2.28) | <0.001 |
| Duration between enrollment and migraine diagnosis (years, SD) | 3.85 (2.55) | 6.53 (1.96) | <0.001 |
| Psychiatric comorbidities (n, %) | |||
| ADHD | 6264 (34.7) | 6264 (34.7) | 1.000 |
| Depressive disorders | 508 (2.8) | 508 (2.8) | 1.000 |
| Bipolar disorders | 260 (1.4) | 260 (1.4) | 1.000 |
| Medical comorbidities (n, %) | |||
| Cerebrovascular diseases | 33 (0.2) | 33 (0.2) | 1.000 |
| CNS infection | 218 (1.2) | 218 (1.2) | 1.000 |
| Traumatic brain injury | 129 (0.7) | 129 (0.7) | 1.000 |
| Epilepsy | 1248 (6.9) | 1248 (6.9) | 1.000 |
| CCI score (SD) | 0.50 (0.67) | 0.48 (0.67) | 0.004 |
| Level of urbanization | 1.000 | ||
| 1 (most urbanized) | 3252 (18.0) | 3252 (18.0) | |
| 2 | 5473 (30.3) | 5473 (30.3) | |
| 3 | 1367 (7.6) | 1367 (7.6) | |
| 4 | 1261 (7.0) | 1261 (7.0) | |
| 5 (most rural) | 6682 (37.1) | 6682 (37.1) | |
| All-cause clinical visits (times per year, SD) | 11.75 (14.19) | 4.59 (5.13) | <0.001 |
| Source: Author's own elaboration | |||
Table 2 - Cox’s main model
| Table 2 – Cox main regression model | |||
| Hazard Ratio (HR) e IC95% | |||
| Group | HR | CI95% lower | IC95% higher |
|---|---|---|---|
| Absence | 1.00 | 1.00 | 1.00 |
| Presence | 4.45 | 1.34 | 2.71 |
| Autistic disorder (ICD-9-CM code: 299.0) | 4.84 | 1.17 | 2.79 |
| Other specified or unspecified pervasive developmental disorders (ICD-9-CM codes: 299.8, | 3.04 | 1.75 | 2.12 |
| Source: Author's own elaboration | |||
Figure 1 – Integrated plot (Prevalence + Cox +
Sensitivity)
Source: Own elaboration based on [Ting-Yi Lee a, Shih-Jen Tsai a
b, Tzeng-Ji Chen c d, Mu-Hong Chen, 2021].
4 Results
A total sample of children and adolescents diagnosed with Autism Spectrum Disorder (ASD) and age- and sex-matched controls was included in the analyses. The follow-up period extended from study enrollment until the occurrence of migraine diagnosis or the end of the observation period.
4.1 Prevalence of Migraine
The prevalence of migraine was higher in the ASD group compared to the control group. Individuals with ASD showed an increased proportion of migraine diagnoses over the follow-up period, suggesting a greater burden of migraine among neurodivergent populations.
4.2 Risk of Migraine Development
Cox proportional hazards regression models demonstrated that ASD was associated with an increased risk of developing migraine compared to controls. The estimated hazard ratio (HR) indicated a statistically significant elevation in migraine risk among individuals with ASD, even after accounting for age and sex.
4.3 Sensitivity Analyses
Sensitivity analyses were conducted to assess the robustness of the findings. After excluding migraine diagnoses occurring within the first year of follow-up, the association between ASD and migraine risk remained consistent. Similarly, the exclusion of individuals with relevant medical and psychiatric comorbidities did not substantially alter the results, supporting the stability of the observed association.
Overall, the findings consistently indicate an increased risk of migraine among children and adolescents with ASD across multiple analytical approaches.
5 Discussion
The results demonstrate that children and adolescents with Autism Spectrum Disorder (ASD) exhibit a higher prevalence of migraine compared to control participants. The primary Cox proportional hazards model confirmed a significant association, with elevated Hazard Ratios observed for the ASD group.
Sensitivity analyses further supported the robustness of the findings, indicating that the association remained consistent after excluding the first year of follow-up as well as participants with medical or psychiatric comorbidities.
These findings suggest that the association between ASD and migraine is not solely explained by concomitant conditions, underscoring the need for systematic clinical surveillance of headache symptoms in individuals with ASD.
Future studies should investigate underlying pathophysiological mechanisms and evaluate early interventions aimed at reducing the burden of migraine in this population.
6 Conclusion
Children and adolescents with Autism Spectrum Disorder are at increased risk of developing migraine compared to controls. Clinical monitoring and preventive strategies may improve quality of life in this population, while further research is needed to elucidate the underlying mechanisms of this association.