Carey Meghan E, Kivumbi Apollo, Rando Juliette, Mesaros A Clementina, Melnyk Stepan, James S Jill, Croen Lisa A, Volk Heather, Lyall Kristen
A.J. Drexel Autism Institute, Drexel University, 3020 Market Street, Suite 560, Philadelphia, PA, 19104, USA.
Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd, Philadelphia, PA, 17104, USA.
Brain Behav Immun Health. 2024 Apr 24;38:100775. doi: 10.1016/j.bbih.2024.100775. eCollection 2024 Jul.
Oxidative stress during pregnancy has been a mechanistic pathway implicated in autism development, yet few studies have examined this association directly. Here, we examined the association of prenatal levels of 8-iso-PGF2α, a widely used measure of oxidative stress, and several neurodevelopmental outcomes related to autism in children. Participants included 169 mother-child pairs from the Early Autism Risk Longitudinal Investigation (EARLI), which enrolled mothers who had an autistic child from a previous pregnancy and followed them through a subsequent pregnancy and until that child reached age 3 years. Maternal urine samples were collected during the second trimester of pregnancy and were later measured for levels of isoprostanes. Child neurodevelopmental assessments included the Mullen Scales of Early Learning (MSEL), the Social Responsiveness Scale (SRS), and the Vineland Adaptive Behavior Scale (VABS), and were conducted around 36 months of age. Primary analyses examined associations between interquartile range (IQR) increases in 8-iso-PGF2α levels, and total composite scores from each assessment using quantile regression. In adjusted analyses, we did not observe statistically significant associations, though estimates suggested modestly lower cognitive scores (β for MSEL = -3.68, 95% CI: -10.09, 2.70), and minor increases in autism-related trait scores (β for SRS T score = 1.68, 95% CI: -0.24, 3.60) with increasing 8-iso-PGF2α. These suggestive associations between decreased cognitive scores and increased autism-related traits with increasing prenatal oxidative stress point to the need for continued investigation in larger samples of the role of oxidative stress as a mechanistic pathway in autism and related neurodevelopmental outcomes.
孕期氧化应激一直被认为是与自闭症发展相关的一种机制途径,但很少有研究直接考察这种关联。在此,我们研究了8-异前列腺素F2α(一种广泛用于衡量氧化应激的指标)的产前水平与儿童自闭症相关的几种神经发育结局之间的关联。研究对象包括169对母婴,来自早期自闭症风险纵向调查(EARLI),该调查招募了曾孕育过自闭症患儿的母亲,并跟踪她们经历后续妊娠,直至孩子3岁。在孕期的第二个月收集母亲的尿液样本,随后检测其中异前列腺素的水平。儿童神经发育评估包括莫伦早期学习量表(MSEL)、社会反应量表(SRS)和文兰适应行为量表(VABS),在36个月左右进行。主要分析使用分位数回归研究8-异前列腺素F2α水平的四分位数间距(IQR)增加与各评估的总综合得分之间的关联。在调整分析中,我们未观察到具有统计学意义的关联,不过估计结果显示,随着8-异前列腺素F2α水平升高,认知得分略有降低(MSEL的β值 = -3.68,95%置信区间:-10.09,2.70),自闭症相关特质得分略有增加(SRS T得分的β值 = 1.68,95%置信区间:-0.24,3.60)。认知得分降低与产前氧化应激增加导致自闭症相关特质增加之间的这些提示性关联表明,需要在更大样本中继续研究氧化应激作为自闭症及相关神经发育结局的一种机制途径所起的作用。