Maternal health during pregnancy plays a major role in shaping health and disease risks in the offspring. The maternal immune activation hypothesis proposes that inflammatory perturbations in utero can affect fetal neurodevelopment, and evidence from human epidemiological studies supports an association between maternal inflammation during pregnancy and offspring neurodevelopmental disorders (NDDs). Diverse maternal inflammatory factors, including obesity, asthma, autoimmune disease, infection and psychosocial stress, are associated with an increased risk of NDDs in the offspring. In addition to inflammation, epigenetic factors are increasingly recognized to operate at the gene–environment interface during NDD pathogenesis. For example, integrated brain transcriptome and epigenetic analyses of individuals with NDDs demonstrate convergent dysregulated immune pathways. In this Review, we focus on the emerging human evidence for an association between maternal immune activation and childhood NDDs, including autism spectrum disorder, attention-deficit/hyperactivity disorder and Tourette syndrome. We refer to established pathophysiological concepts in animal models, including immune signalling across the placenta, epigenetic ‘priming’ of offspring microglia and postnatal immune–brain crosstalk. The increasing incidence of NDDs has created an urgent need to mitigate the risk and severity of these conditions through both preventive strategies in pregnancy and novel postnatal therapies targeting disease mechanisms.

怀孕期间的母亲健康在塑造后代的健康和疾病风险方面起着重要作用。母体免疫激活假说提出，子宫内的炎症扰动会影响胎儿神经发育，人类流行病学研究的证据支持妊娠期间母体炎症与后代神经发育障碍 (NDD) 之间的关联。多种母体炎症因素，包括肥胖、哮喘、自身免疫性疾病、感染和社会心理压力，与后代患 NDDs 的风险增加有关。除了炎症，越来越多的人认识到表观遗传因素在 NDD 发病机制中在基因-环境界面上起作用。例如，对患有 NDD 的个体进行的脑转录组和表观遗传学分析表明，免疫通路趋同性失调。在这篇综述中，我们关注新出现的人类证据，证明母体免疫激活与儿童 NDD 之间存在关联，包括自闭症谱系障碍、注意力缺陷/多动障碍和图雷特综合征。我们参考动物模型中已建立的病理生理学概念，包括跨胎盘的免疫信号、后代小胶质细胞的表观遗传“启动”和产后免疫-大脑串扰。NDDs 发病率的增加迫切需要通过怀孕期间的预防策略和针对疾病机制的新型产后疗法来减轻这些疾病的风险和严重程度。我们专注于新出现的人类证据，证明母体免疫激活与儿童 NDD 之间存在关联，包括自闭症谱系障碍、注意力缺陷/多动障碍和图雷特综合征。我们参考动物模型中已建立的病理生理学概念，包括跨胎盘的免疫信号、后代小胶质细胞的表观遗传“启动”和产后免疫-大脑串扰。NDDs 发病率的增加迫切需要通过怀孕期间的预防策略和针对疾病机制的新型产后疗法来减轻这些疾病的风险和严重程度。我们专注于新出现的人类证据，证明母体免疫激活与儿童 NDD 之间存在关联，包括自闭症谱系障碍、注意力缺陷/多动障碍和图雷特综合征。我们参考动物模型中已建立的病理生理学概念，包括跨胎盘的免疫信号、后代小胶质细胞的表观遗传“启动”和产后免疫-大脑串扰。NDDs 发病率的增加迫切需要通过怀孕期间的预防策略和针对疾病机制的新型产后疗法来减轻这些疾病的风险和严重程度。我们参考动物模型中已建立的病理生理学概念，包括跨胎盘的免疫信号、后代小胶质细胞的表观遗传“启动”和产后免疫-大脑串扰。NDDs 发病率的增加迫切需要通过怀孕期间的预防策略和针对疾病机制的新型产后疗法来减轻这些疾病的风险和严重程度。我们参考动物模型中已建立的病理生理学概念，包括跨胎盘的免疫信号、后代小胶质细胞的表观遗传“启动”和产后免疫-大脑串扰。NDDs 发病率的增加迫切需要通过怀孕期间的预防策略和针对疾病机制的新型产后疗法来减轻这些疾病的风险和严重程度。