Neonatal hair metabolome of birthweight discordant twins is associated with neurobehavioral impairments at 2-3 years of age

Abstract

Objective: To characterize the metabolic variation in neonatal hair samples associated with intrauterine growth discordance in dichorionic-diamniotic (DCDA) twins and to evaluate the effects of specific metabolic alterations on later neurobehavioural outcomes in infancy. Design: Cohort-based case-control study Setting: Peking University Third Hospital Population: DCDA twins with birth weight discordance(DCDA-D) and birthweight concordance (DCDA-C) within a twin cohort recruited between September 2017 and December 2018 in Beijing, China. Methods: A specific hair metabolic profile of 14 pairs of DCDA-D twins was revealed using gas chromatography-mass spectrometry by comparing that of 28 pairs of DCDA-C twins. Pearson’s correlation was used to assess the relationship between the neonatal hair metabolome and neurocognitive outcomes, assessed using the Ages and the Infant’s Stages Questionnaires, third edition (ASQ-3) at 2 or 3 years of age. Main outcome measure: neonatal hair metabolome and long-term neurodevelopment. Results: A total of seventeen hair metabolites were significantly different within DCDA-D twin pairs compared to DCDA-C twins. Particularly, reduced levels of cysteine, threonine, and leucine were identified in both the larger and smaller DCDA-D twins compared with DCDA-C twins. The deregulated metabolic pathways including cysteine, methionine, aminoacyl-tRNA, nicotinate, and nicotinamide metabolism biosynthesis pathways in DCDA-D groups were positively correlated with infant neurocognitive development at 2 or 3 years of age, especially in problem-solving domains. Conclusion: Neonatal hair metabolic variations in utero of growth discordance in DCDA twins may be associated with poor neurocognitive development. Metabolome profiles of hair may be novel predictors of infant neurodevelopment longitudinally.