Díaz-Pons Alexandre, Castaño-Castaño Sergio, Ortiz-García de la Foz Víctor, Ayesa-Arriola Rosa
Departamento de Investigación en Enfermedades Mentales, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, 39011, España.
Escuela de Doctorado de la Universidad de Cantabria (EDUC), Universidad de Cantabria (UC), Santander, 39005, España.
Eur Child Adolesc Psychiatry. 2025 Aug 27. doi: 10.1007/s00787-025-02837-z.
This study examines the effects of SARS-CoV-2-induced maternal immune activation (MIA) on early neurodevelopment, focusing on sex-specific vulnerabilities related to early behavioral and regulatory functions, which may be precursors to later developmental or cognitive challenges. A total of 107 mother-infant dyads from the COGESTCOV-19 study were analyzed to assess neurodevelopmental outcomes in male and female infants at six weeks using the Neonatal Behavioral Assessment Scale (NBAS). Maternal and newborn cytokine levels-specifically interleukin-6 (IL-6), interleukin-10 (IL-10), and the IL-6/IL-10 ratio-were measured at the first prenatal visit at the time of study enrolment and at birth to evaluate inflammatory responses and homeostatic balance. Neither maternal nor newborn cytokine levels differed significantly between cases and controls. Significant sex-specific differences were observed in neurodevelopmental outcomes related to maternal SARS-CoV-2 exposure. Female infants exposed in utero showed significantly reduced performance in orientation and state regulation measures compared to exposed male infants and unexposed male and female controls. The findings suggest that SARS-CoV-2-induced MIA - not limited to IL-6/IL-10 balance - may have a differential impact on early neurodevelopment based on sex, underscoring the necessity for targeted interventions to mitigate these effects. Future studies should explore the mechanisms underlying these sex-specific differences and their long-term implications for neurodevelopment.
本研究考察了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）诱导的母体免疫激活（MIA）对早期神经发育的影响，重点关注与早期行为和调节功能相关的性别特异性脆弱性，这些可能是后期发育或认知挑战的先兆。对来自COGESTCOV-19研究的107对母婴进行了分析，使用新生儿行为评估量表（NBAS）评估六周龄男婴和女婴的神经发育结果。在研究入组时的首次产前检查以及出生时测量母体和新生儿的细胞因子水平，特别是白细胞介素-6（IL-6）、白细胞介素-10（IL-10）以及IL-6/IL-10比值，以评估炎症反应和内稳态平衡。病例组和对照组的母体及新生儿细胞因子水平均无显著差异。在与母体SARS-CoV-2暴露相关的神经发育结果中观察到了显著的性别特异性差异。与暴露的男婴以及未暴露的男婴和女婴对照组相比，子宫内暴露的女婴在定向和状态调节测量中的表现显著降低。研究结果表明，SARS-CoV-2诱导的MIA——不限于IL-6/IL-10平衡——可能基于性别对早期神经发育产生不同影响，强调了采取针对性干预措施减轻这些影响的必要性。未来的研究应探索这些性别特异性差异的潜在机制及其对神经发育的长期影响。
