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The gut microbiota of preterm infants is affected by perinatal factors and, in turn, may impact upon infant health. In this study, we collected fecal samples at Day-10 (D10) and 4-months corrected-age (4M) from 227 moderate–late preterm (MLPT) babies enrolled in a randomized controlled trial of nutritional management. A total of 320 samples underwent 16S amplicon sequencing, and shotgun metagenomic sequencing was performed on 94 samples from the 4M time point. The microbiome of babies whose families lived in lower socioeconomic status (SES) areas exhibited a significantly higher microbial alpha diversity at D10 (Wilcoxon test , p  = 0.021), greater abundance of  Bifidobacterium  (linear model, q = 0.020) at D10 and  Megasphaera  (q = 0.031) at 4M. Hospital of birth explained 5.2% of the observed variance in 4M samples (PERMANOVA,  p  = 0.038), with  Staphylococcus aureus  more abundant in fecal samples from babies born in Middlemore hospital (linear model, q = 0.016). Maternal antibiotic (Wilcoxon test,  p  = 0.013) and probiotic ( p  = 0.04) usage within the four-week period before sample collection was associated with a reduction in the alpha diversity of D10 samples. Infant probiotic intake explained 2.1% (PERMANOVA,  p  = 0.021) of the variance in the D10 microbial profile with increased  Lactobacillus  (linear model, q = 1.1 × 10 −10 ) levels. At 4M, the microbiome of infants who were breastmilk fed had reduced alpha diversity when compared to non-breastmilk fed infants (Wilcoxon test,  p  < 0.05). Although causality cannot be inferred within our study, we conclude that in MLPT babies, maternal socioeconomic factors, as well as the perinatal medical environment and nutrition impact on the development of the newborn microbiome.

Factors Associated With the Microbiome in Moderate–Late Preterm Babies: A Cohort Study From the DIAMOND Randomized Controlled Trial