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. 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. 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). 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. 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.

中文翻译：

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出生窒息和热性惊厥对自闭症谱系障碍的叠加相互作用：一项基于人群的研究

自闭症谱系障碍 (ASD) 是一种普遍存在的神经发育障碍，可显着影响个人的社会融入和适应能力。确定与 ASD 相关的关键因素至关重要。最近的研究将出生窒息 (BA) 和热性惊厥 (FS) 分别与较高的自闭症谱系障碍 (ASD) 患病率联系起来。然而，对于 BA 和 FS 的相互作用及其与 ASD 的关系尚未进行调查。本研究主要探讨 ASD 背景下 BA 和 FS 之间的交互作用。采用多阶段分层整群抽样方法，我们于2014年6月至2015年6月期间首次招募了84,934名上海3-12岁儿童，最终纳入了74,251名符合排除标准的儿童。在控制相关协变量后，使用逻辑回归模型来估计交互作用。计算归因比例（AP）、交互作用导致的相对超额风险（RERI）、协同指数（SI）和乘性尺度交互作用，以确定交互作用。在总共 74,251 名儿童中，192 名（0.26%）被诊断患有 ASD。单独患有 BA 的儿童 ASD 的调整后比值比为 3.82（95% 置信区间 [CI] 2.42-6.02），单独 FS 为 3.06（95%CI 1.48-6.31），合并 BA 和 FS 为 21.18（95%CI） 9.10–49.30），与没有 BA 或 FS 的儿童相比。 BA 和 FS 之间的加性交互作用具有统计学意义（P < 0.001），而乘性交互作用则具有统计学意义（P > 0.05）。本研究只能证明BA和FS的相互作用与ASD之间的关系，但不能证明因果关系。动物大脑实验对于揭示其神经机制是必要的。需要更大的样本量、持续监测和详细的 FS 分类来确认 ASD 中的 BA-FS 相互作用。在这项广泛的横断面研究中，BA 和 FS 均与 ASD 显着相关。这些因素的共存与自闭症谱系障碍患病率的叠加增加有关，超过了每个单独因素的累积风险。