Integrated multi-omics analysis to explore correlations among cord blood IGF-1 levels, metabolomic profiles, and meconium gut microbiota in small-for-gestational-age neonates

Background Small for gestational age (SGA) infants carry high risks of neonatal complications and lifelong metabolic disorders. This study explored correlations among cord blood IGF-1, cord blood metabolome, and meconium microbiota in SGA neonates to clarify the underlying pathophysiology. Methods We consecutively recruited 113 term newborns (53 SGA, 60 AGA) delivered at Hainan Women and Children's Medical Centre from June 2024 to March 2025. Cord blood IGF-1 was tested via chemiluminescence. UHPLC-MS/MS untargeted metabolomics and 16S rRNA high-throughput sequencing were applied to characterize cord blood metabolites and meconium microbiota. Intergroup differences and partial Spearman correlations across IGF-1, metabolites, microbes and birth indices were analyzed, adjusting for gestational age, infant sex, and maternal delivery mode,where applicable. Results (1) SGA infants had markedly lower cord blood IGF-1 ( P < 0.001), which positively correlated with birth weight and length. (partial Spearman r = 0.634 and 0.494, respectively, P < 0.001, after adjusting for gestational age, sex, and maternal BMI). (2) Two groups presented distinct metabolic profiles. SGA infants showed depleted glycerophospholipids, elevated chlorobenzene pollutants, and altered pathways involving bile secretion, choline and steroid metabolism. (3) No alpha diversity difference existed, yet beta diversity confirmed divergent microbial structures (R 2 = 0.0284, P = 0.046). SGA overrepresented Clostridium and Klebsiella , with reduced facultative pioneer bacteria. (4) SGA-enriched anaerobes negatively correlated with birth size and IGF-1, while chlorobenzene levels were positively associated with these pathogenic genera. Conclusions SGA neonates feature suppressed IGF-1, intrauterine metabolic disorders and disordered initial gut colonization. Disturbed prenatal metabolism and pollutant exposure may jointly drive aberrant early microbiota development in growth-restricted newborns. The cross-sectional design precludes causal inference, and the chlorobenzene finding warrants independent validation.