Effect of Antibiotic Use Within First 48 Hours of Life on the Preterm Infant Microbiome: A Randomized Clinical Trial

Abstract

This randomized clinical trial investigates whether withholding the standard 48 hours of intravenous empirical antibiotics immediately after birth in preterm infants protects the developing microbiome and improves clinical outcomes.

Figure 1.. CONSORT Figure

Figure depicting patient characteristics of the placebo and treatment groups of study. Inclusion criteria for study as per https://clinicaltrials.gov/ct2/show/NCT02477423 included delivery at 28 weeks' to 34 weeks and 6 days’ gestation without congenital anomalies, rupture of membranes greater than 18 hours, evidence of maternal chorioamnionitis, 5-minute Apgar score less than 5, fraction of inspired oxygen requirement greater than 40%, immature to total neutrophil ratio (I:T) greater than 0.2 on complete blood cell count and differential (CBC/diff) at less than 6 hours of life, seizures or requirement for cardiovascular support in the first 3 hours of life. Sites: the University of Chicago Comer Children’s Hospital, Chicago, Illinois, and Northshore University HealthSystem Evanston Hospital, Evanston, Illinois, from 2015 to 2018. Abx indicates antibiotics.

Figure 2.. Effects of Placebo or Antibiotic Treatment on Early Fecal Microbiome Composition and Intestinal Development

16S rRNA gene sequencing. A, No significant difference in β-diversity at all examined taxonomic levels by permutational multivariate analysis of variance shown in nonmetric multidimensional scaling plot. B, Most phyla (only >1% mean relative abundance presented) were not significantly different between placebo (Ab⁻) and antibiotic (Ab⁺), as determined by analysis of variance with patient as a random effect, except Actinobacteriota. C and D, Immunohistochemistry staining of the ileal samples of 2-week-old mice colonized with donor microbiota from Ab⁻ and Ab⁺ groups (n = 4 to 6 mice). No significant difference in villus length or crypt depth (average of 12 villi or crypts per animal). D, No significant difference in NF-κB activation quantified by percentage of phosphorylated p65 subunit (pp65) positive nuclei/total nuclei. Results are presented as mean (SEM) in C and D. The t test was used to compare between Ab⁻ and Ab⁺. NMDS indicates nonmetric multidimensional scaling. ^aP < .05.