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Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based
Yi Mao1, Xindi Lin1, Yuhan Wu1
1Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Insights
Birth asphyxia (BA) and febrile seizures (FS) are linked to increased autism spectrum disorder (ASD) risk. Their combined presence significantly elevates ASD prevalence more than individual factors, highlighting an additive interaction.
Area of Science:
- Neurodevelopmental disorders
- Pediatric health
- Epidemiology
Background:
- Autism Spectrum Disorder (ASD) significantly impacts social integration.
- Previous research indicates separate links between birth asphyxia (BA) and febrile seizures (FS) with higher ASD prevalence.
- The interactive effect of BA and FS on ASD risk remains under-investigated.
Purpose of the Study:
- To explore the interactive effect of birth asphyxia and febrile seizures in the context of Autism Spectrum Disorder.
- To quantify the combined risk of BA and FS for ASD.
Main Methods:
- A multi-stage stratified cluster sampling method was used, recruiting 84,934 children aged 3-12 years in Shanghai.
- Logistic regression models were employed to estimate interaction effects, controlling for covariates.
- Attributable proportion (AP), relative excess risk due to interaction (RERI), synergy index (SI), and multiplicative-scale interaction were calculated.
Main Results:
- Out of 74,251 children, 192 (0.26%) were diagnosed with ASD.
- The adjusted odds ratio for ASD was 3.82 for BA alone, 3.06 for FS alone, and significantly higher at 21.18 for comorbid BA and FS.
- A statistically significant additive interaction (P < 0.001) was observed between BA and FS, while the multiplicative interaction was not significant (P > 0.05).
Conclusions:
- Both BA and FS are significantly associated with ASD.
- The coexistence of BA and FS demonstrates a statistically significant additive interaction, substantially increasing ASD prevalence beyond the sum of individual risks.
- Further research with larger sample sizes and detailed classifications is needed to confirm these findings and explore underlying neural mechanisms.
Background:
Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD.
Methods:
Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect.
Results:
Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05).
Limitations:
This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD.
Conclusion:
In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor.
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Related Concept Videos
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:13Seizures: Classification
Seizures are typically classified into two main categories: focal and generalized seizures.
Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types: