Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort studyResearch in context
Kristina Vacy,
Sarah Thomson,
Archer Moore,
Alex Eisner,
Sam Tanner,
Cindy Pham,
Richard Saffrey,
Toby Mansell,
David Burgner,
Fiona Collier,
Peter Vuillermin,
Martin O’Hely,
Wah Chin Boon,
Peter Meikle,
Satvika Burugupalli,
Anne-Louise Ponsonby,
Mimi L.K. Tang,
Lawrence Gray,
Sarath Ranganathan,
Peter Sly,
Jochen Mueller,
Terry Dwyerm,
John Carlin
Affiliations
Kristina Vacy
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
Sarah Thomson
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia
Archer Moore
Melbourne School of Mathematics and Statistics, University of Melbourne, Parkville 3010, Australia
Alex Eisner
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia
Sam Tanner
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia
Cindy Pham
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville 3010, Australia; Department of Paediatrics, University of Melbourne, Parkville 3010, Australia
Richard Saffrey
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville 3010, Australia; Department of Paediatrics, University of Melbourne, Parkville 3010, Australia
Toby Mansell
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville 3010, Australia; Department of Paediatrics, University of Melbourne, Parkville 3010, Australia
David Burgner
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville 3010, Australia; Department of Paediatrics, University of Melbourne, Parkville 3010, Australia; Department of Paediatrics, Monash University, Clayton 3168, Australia
Fiona Collier
Child Health Research Unit, Barwon Health, Geelong 3220, Australia; School of Medicine, Deakin University, Geelong 3220, Australia
Peter Vuillermin
Child Health Research Unit, Barwon Health, Geelong 3220, Australia
Martin O’Hely
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville 3010, Australia; School of Medicine, Deakin University, Geelong 3220, Australia
Wah Chin Boon
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia
Peter Meikle
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne 3004, Australia; Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Bundoora, VIC 3086, Australia
Satvika Burugupalli
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne 3004, Australia
Anne-Louise Ponsonby
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville 3010, Australia; Department of Paediatrics, University of Melbourne, Parkville 3010, Australia; Corresponding author. Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, Parkville, VIC 3052, Australia.
Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: 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.
