Biomed Environ Sci. 2026 Aug 20;39(8):937-952. doi: 10.3967/bes2026.075.
ABSTRACT
OBJECTIVE: Selective fetal growth restriction (sFGR) in dichorionic-diamniotic (DCDA) twins is associated with the risk of adverse neurodevelopment; however, the underlying metabolic dysregulation remains poorly characterized. We aimed to characterize the neonatal hair metabolome associated with sFGR in DCDA twins and assess its predictive value for long-term neurodevelopment.
METHODS: Forty-two pairs of DCDA twins were stratified into the sFGR-DCDA (twins with birth weight [BW] discordance) and DCDA-C (twins with BW concordance) groups. Neonatal hair metabolites were profiled using gas chromatography-mass spectrometry (GC-MS). Pathway analysis and machine learning were used to identify metabolic signatures predictive of neurodevelopment, which were assessed using the Ages and Stages Questionnaire (Third Edition) at 2-3 and 5-6 years of age.
RESULTS: The smaller neonates in the sFGR-DCDA group (DCDA-S) showed significant downregulation of cysteine, methionine, glutathione, aminoacyl-tRNA, and nicotinate and nicotinamide metabolism in comparison with the neonates in the DCDA-C group. Reduced glutathione and aminoacyl-tRNA pathway activity correlated with lower problem-solving scores. An exploratory machine learning model incorporating pantothenate and coenzyme A biosynthesis, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism showed a preliminary discriminatory capacity for low personal-social scores in DCDA-S children at 2-3 years of age.
CONCLUSION: Neonatal hair metabolomics in DCDA-S children reflect intrauterine disturbances in antioxidant and protein synthesis pathways associated with later neurodevelopmental outcomes, providing a non-invasive window into metabolic programming in sFGR.
PMID:42687614 | DOI:10.3967/bes2026.075
