Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia; Melbourne School of Population and Global Health, University of Melbourne, Parkville 3010, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia.
EBioMedicine. 2024 Feb;100:104949. doi: 10.1016/j.ebiom.2023.104949. Epub 2024 Jan 9.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions with early life origins. Alterations in blood lipids have been linked to ADHD and ASD; however, prospective early life data are limited. This study examined (i) associations between the cord blood lipidome and ADHD/ASD symptoms at 2 years of age, (ii) associations between prenatal and perinatal predictors of ADHD/ASD symptoms and cord blood lipidome, and (iii) mediation by the cord blood lipidome.
From the Barwon Infant Study cohort (1074 mother-child pairs, 52.3% male children), child circulating lipid levels at birth were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. These were clustered into lipid network modules via Weighted Gene Correlation Network Analysis. Associations between lipid modules and ADHD/ASD symptoms at 2 years, assessed with the Child Behavior Checklist, were explored via linear regression analyses. Mediation analysis identified indirect effects of prenatal and perinatal risk factors on ADHD/ASD symptoms through lipid modules.
The acylcarnitine lipid module is associated with both ADHD and ASD symptoms at 2 years of age. Risk factors of these outcomes such as low income, Apgar score, and maternal inflammation were partly mediated by higher birth acylcarnitine levels. Other cord blood lipid profiles were also associated with ADHD and ASD symptoms.
This study highlights that elevated cord blood birth acylcarnitine levels, either directly or as a possible marker of disrupted cell energy metabolism, are on the causal pathway of prenatal and perinatal risk factors for ADHD and ASD symptoms in early life.
The foundational work and infrastructure for the BIS was sponsored by the Murdoch Children's Research Institute, Deakin University, and Barwon Health. Subsequent funding was secured from the Minderoo Foundation, the European Union's Horizon 2020 research and innovation programme (ENDpoiNTs: No 825759), National Health and Medical Research Council of Australia (NHMRC) and Agency for Science, Technology and Research Singapore [APP1149047], The William and Vera Ellen Houston Memorial Trust Fund (via HOMER Hack), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O'Brien Memorial Asthma Foundation, the Our Women Our Children's Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, Geelong Medical and Hospital Benefits Association, Vanguard Investments Australia Ltd, the Percy Baxter Charitable Trust, and Perpetual Trustees.
注意力缺陷多动障碍（ADHD）和自闭症谱系障碍（ASD）是具有早期生命起源的神经发育障碍。血液脂质的改变与 ADHD 和 ASD 有关；然而，前瞻性的早期生活数据有限。本研究探讨了（i）脐带血脂质组与 2 岁时 ADHD/ASD 症状之间的关系，（ii）ADHD/ASD 症状的产前和围产期预测因素与脐带血脂质组之间的关系，以及（iii）脐带血脂质组的中介作用。
来自 Barwon 婴儿研究队列（1074 对母婴，52.3%的男婴），使用超高效液相色谱-串联质谱法分析出生时儿童循环脂质水平。通过加权基因相关网络分析，将这些脂质聚类为脂质网络模块。通过线性回归分析，探讨了脂质模块与 2 岁时 ADHD/ASD 症状（用儿童行为检查表评估）之间的关系。中介分析确定了产前和围产期危险因素通过脂质模块对 ADHD/ASD 症状的间接影响。
酰基辅酶 A 脂质模块与 2 岁时的 ADHD 和 ASD 症状均相关。这些结果的危险因素，如低收入、阿普加评分和母亲炎症，部分通过较高的出生酰基辅酶 A 水平来介导。其他脐带血脂质谱也与 ADHD 和 ASD 症状有关。
本研究强调，脐带血中出生时升高的酰基辅酶 A 水平，无论是直接升高还是作为细胞能量代谢紊乱的可能标志物，都可能与 ADHD 和 ASD 症状的产前和围产期危险因素有关。
BIS 的基础工作和基础设施由默多克儿童研究所、迪肯大学和巴旺健康公司赞助。随后的资金来自米尔杜拉基金会、欧盟地平线 2020 研究和创新计划（ENDpoiNTs：No 825759）、澳大利亚国家卫生与医学研究理事会（NHMRC）和新加坡科学、技术和研究局[APP1149047]、威廉和维拉·艾伦·休斯顿纪念信托基金（通过 HOMER Hack）、谢泼德基金会、克莱尔·麦金农信托基金、斯科比和谢泼德基金会、肖恩·奥布赖恩纪念哮喘基金会、我们的妇女我们的儿童基金筹款委员会巴旺健康、乔治敦扶轮社、伊尔汉食物过敏基金会、吉朗医疗和医院福利协会、先锋投资澳大利亚有限公司、珀西·巴克斯特慈善信托基金和永久受托人。
