Neonatal Hair Metabolic Signatures of Selective Fetal Growth Restriction in DCDA Twins are Linked to Adverse Neurobehavioral Outcomes at Infancy and Early Childhood.

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.