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Maternal preconception circulating blood biomarker mixtures, child behavioural symptom scores and the potential mediating role of neonatal brain microstructure: the S-PRESTO cohort

Maternal preconception circulating blood biomarker mixtures, child behavioural symptom scores and the potential mediating role of neonatal brain microstructure: the S-PRESTO cohort
Maternal preconception circulating blood biomarker mixtures, child behavioural symptom scores and the potential mediating role of neonatal brain microstructure: the S-PRESTO cohort
Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed.
Huang, Jian
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Tan, Ai Peng
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Law, Evelyn C.
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Godfrey, Keith
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Qiu, Anqi
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Daniel, Lourdes Mary
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Fortier, Marielle
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Tan, Kok Hian
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Chan, Jerry Kok Yen
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Cameron-Smith, David
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Chong, Yap-Seng
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Chan, Shiao-Yng
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Eriksson, Johan G.
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Meaney, Michael J.
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Huang, Jonathan
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Huang, Jian
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Tan, Ai Peng
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Law, Evelyn C.
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Godfrey, Keith
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Qiu, Anqi
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Daniel, Lourdes Mary
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Fortier, Marielle
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Tan, Kok Hian
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Chan, Jerry Kok Yen
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Cameron-Smith, David
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Chong, Yap-Seng
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Chan, Shiao-Yng
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Eriksson, Johan G.
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Meaney, Michael J.
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Huang, Jonathan
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Huang, Jian, Tan, Ai Peng, Law, Evelyn C., Godfrey, Keith, Qiu, Anqi, Daniel, Lourdes Mary, Fortier, Marielle, Tan, Kok Hian, Chan, Jerry Kok Yen, Cameron-Smith, David, Chong, Yap-Seng, Chan, Shiao-Yng, Eriksson, Johan G., Meaney, Michael J. and Huang, Jonathan (2023) Maternal preconception circulating blood biomarker mixtures, child behavioural symptom scores and the potential mediating role of neonatal brain microstructure: the S-PRESTO cohort. Translational Psychiatry, 13 (1), [38]. (doi:10.1038/s41398-023-02332-6).

Record type: Article

Abstract

Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed.

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Accepted/In Press date: 20 January 2023
Published date: 3 February 2023
Additional Information: Open Access - CC-BY

Identifiers

Local EPrints ID: 474505
URI: http://eprints.soton.ac.uk/id/eprint/474505
PURE UUID: eaa31909-cdb0-40ab-b6e6-d4ff96aa8c9a
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

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Date deposited: 23 Feb 2023 17:40
Last modified: 17 Mar 2024 02:38

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Contributors

Author: Jian Huang
Author: Ai Peng Tan
Author: Evelyn C. Law
Author: Keith Godfrey ORCID iD
Author: Anqi Qiu
Author: Lourdes Mary Daniel
Author: Marielle Fortier
Author: Kok Hian Tan
Author: Jerry Kok Yen Chan
Author: David Cameron-Smith
Author: Yap-Seng Chong
Author: Shiao-Yng Chan
Author: Johan G. Eriksson
Author: Michael J. Meaney
Author: Jonathan Huang

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