TY - JOUR

T1 - Delayed Motor Milestones Achievement in Infancy Associates with Perturbations of Amino Acids and Lipid Metabolic Pathways

AU - Vinding, Rebecca Kofod

AU - Rago, Daniela

AU - Kelly, Rachel S.

AU - Gürdeniz, Gözde

AU - Rasmussen, Morten Arendt

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Litonjua, Augusto A.

AU - Weiss, Scott T.

AU - Lasky-Su, Jessica

AU - Bisgaard, Hans

AU - Chawes, Bo Lund

PY - 2020

Y1 - 2020

N2 - The relationship between developmental milestone achievement in infancy and later cognitive function and mental health is well established, but underlying biochemical mechanisms are poorly described. Our study aims to discover pathways connected to motor milestone achievement during infancy by using untargeted plasma metabolomic profiles from 571 six-month-old children in connection with age of motor milestones achievement (Denver Developmental Index) in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) mother-child cohort. We used univariate regression models and multivariate modelling (Partial Least Squares Discriminant Analysis: PLS-DA) to examine the associations and the VDAART (Vitamin D Antenatal Asthma Reduction Trial) cohort for validation. The univariate analyses showed 62 metabolites associated with gross-motor milestone achievement (p<0.05) as well as the PLS-DA significantly differentiated between slow and fast milestone achievers (AUC = 0.87,p= 0.01). Higher levels of tyramine-O-sulfate in the tyrosine pathway were found in the late achievers in COPSAC (p= 0.0002) and in VDAART (p= 0.02). Furthermore, we observed that slow achievers were characterized by higher levels of fatty acids and products of fatty acids metabolism including acyl carnitines. Finally, we also observed changes in the lysine, histidine, glutamate, creatine and tryptophan pathways. Observing these metabolic changes in relation to gross-motor milestones in the first year of life, may be of importance for later cognitive function and mental health.

AB - The relationship between developmental milestone achievement in infancy and later cognitive function and mental health is well established, but underlying biochemical mechanisms are poorly described. Our study aims to discover pathways connected to motor milestone achievement during infancy by using untargeted plasma metabolomic profiles from 571 six-month-old children in connection with age of motor milestones achievement (Denver Developmental Index) in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) mother-child cohort. We used univariate regression models and multivariate modelling (Partial Least Squares Discriminant Analysis: PLS-DA) to examine the associations and the VDAART (Vitamin D Antenatal Asthma Reduction Trial) cohort for validation. The univariate analyses showed 62 metabolites associated with gross-motor milestone achievement (p<0.05) as well as the PLS-DA significantly differentiated between slow and fast milestone achievers (AUC = 0.87,p= 0.01). Higher levels of tyramine-O-sulfate in the tyrosine pathway were found in the late achievers in COPSAC (p= 0.0002) and in VDAART (p= 0.02). Furthermore, we observed that slow achievers were characterized by higher levels of fatty acids and products of fatty acids metabolism including acyl carnitines. Finally, we also observed changes in the lysine, histidine, glutamate, creatine and tryptophan pathways. Observing these metabolic changes in relation to gross-motor milestones in the first year of life, may be of importance for later cognitive function and mental health.

KW - motor milestones

KW - metabolomics

KW - children

KW - neurodevelopment

KW - HYDROXYLYSYL GLYCOSIDES

KW - SCHIZOPHRENIA

KW - BIOMARKERS

KW - EXERCISE

KW - IDENTIFICATION

KW - CREATININE

KW - MUTATION

KW - COLLAGEN

KW - SERUM

KW - LEADS

U2 - 10.3390/metabo10090337

DO - 10.3390/metabo10090337

M3 - Journal article

C2 - 32824932

VL - 10

JO - Metabolites

JF - Metabolites

SN - 2218-1989

IS - 9

M1 - 337

ER -