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

Abstract

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.

Diet‐associated vertically transferred metabolites and risk of asthma, allergy, eczema, and infections in early childhood

“…An association between maternal dietary intake during pregnancy and the newborn child's health has been proposed from several observational studies 1,2 . In particular, pregnancy supplementation regimes have emphasized this mother–child link by demonstrating protective effects on the child's risk of developing asthma and infections from different micronutrients 3–5 .…”

“…An association between maternal dietary intake during pregnancy and the newborn child's health has been proposed from several observational studies. 1,2 In particular, pregnancy supplementation regimes have emphasized this mother-child link by demonstrating protective effects on the child's risk of developing asthma and infections from different micronutrients. [3][4][5] These effects are mainly hypothesized to be explained by optimizing the nutrient supply during the rapid growth period of the fetus where the organs and the immune system develop and mature, which has also been referred to as the first window of opportunity.…”

Vertical Transfer of Metabolites Detectable from Newborn’s Dried Blood Spot Samples Using UPLC-MS: A Chemometric Study

“…During pregnancy, the mother and child are exposed to the same nutrients intake and to some extent the same environment. Thus, environmental factors and nutritional status during pregnancy and lactation can have effects on the baby's health including brain development [3], motor milestones achievement [4], digestive tract development [5], metabolism [6], and immune maturation [7]. Additionally, the life changing event of birth including mode of delivery (vaginal or cesarean section) as well as gestational age, also have lifelong effects [8,9].…”