TY - JOUR
T1 - Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years
T2 - a prospective birth cohort study
AU - Vacy, Kristina
AU - Thomson, Sarah
AU - Moore, Archer
AU - Eisner, Alex
AU - Tanner, Sam
AU - Pham, Cindy
AU - Saffrey, Richard
AU - Mansell, Toby
AU - Burgner, David
AU - Collier, Fiona
AU - Vuillermin, Peter
AU - O'Hely, Martin
AU - Boon, Wah Chin
AU - Meikle, Peter
AU - Burugupalli, Satvika
AU - Ponsonby, Anne Louise
AU - Tang, Mimi L.K.
AU - Gray, Lawrence
AU - Ranganathan, Sarath
AU - Sly, Peter
AU - Mueller, Jochen
AU - Dwyerm, Terry
AU - Carlin, John
AU - the Barwon Infant Study Investigator Group
N1 - Funding Information:
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.The authors would like to express their gratitude to the BIS participants for their significant contributions to this project. Further, they extend their thanks to both the current and past staff for their tireless work in participant recruitment, cohort maintenance, as well as the procurement and processing of data and biospecimens. 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. The Cotton On Foundation and Creative Force offered their support in-kind. The sponsors of the study did not participate in the data collection, analysis, or interpretation, the drafting of the report, or the decision to submit the report for publication. Research activities at Murdoch Children's Research Institute are sustained by the Operational Infrastructure Support Program from the Victorian Government. The other members of the BIS Investigator Group are Mimi LK Tang, Lawrence Gray, Sarath Ranganathan, Peter Sly and Jochen Mueller. We thank Terry Dwyer and John Carlin for their past work as foundation investigators in the Barwon Infant Study.
Funding Information:
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 . The Cotton On Foundation and Creative Force offered their support in-kind. The sponsors of the study did not participate in the data collection, analysis, or interpretation, the drafting of the report, or the decision to submit the report for publication. Research activities at Murdoch Children's Research Institute are sustained by the Operational Infrastructure Support Program from the Victorian Government.
Publisher Copyright:
© 2023
PY - 2024/2
Y1 - 2024/2
N2 - 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.
AB - 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.
KW - Acylcarnitine
KW - Attention-deficit/hyperactivity disorder symptoms
KW - Autism spectrum disorder symptoms
KW - Cord blood
KW - Fatty acids
KW - Lipidomics
UR - http://www.scopus.com/inward/record.url?scp=85182355134&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2023.104949
DO - 10.1016/j.ebiom.2023.104949
M3 - Article
C2 - 38199043
AN - SCOPUS:85182355134
SN - 2352-3964
VL - 100
JO - EBioMedicine
JF - EBioMedicine
M1 - 104949
ER -