Routine Early Antibiotic Use in SymptOmatic Preterm Neonates: A Pilot Randomized Controlled Trial

Ruoss, J. Lauren; Bazacliu, Catalina; Russell, Jordan T.; Cruz, Diomel de la; Li, Nan; Gurka, Matthew J.; Filipp, Stephanie L.; Polin, Richard A.; Triplett, Eric W.; Neu, Josef

doi:10.1016/j.jpeds.2020.09.056

Cited by 15 publications

(14 citation statements)

References 24 publications

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“…Seven infants had no samples due to early mortality. Eligible infants were enrolled into groups based on previously described enrollment criteria 30 : group A-antibiotics indicated (n = 28), group B-antibiotics not indicated (n = 11), and group C-eligible for randomization (n = 52). Twenty-six infants were from group C1 (antibiotics in first 48 h) and 14 infants were from group C2 and did not receive antibiotics 48 h after birth.…”

Section: Resultsmentioning

confidence: 99%

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Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

Russell

Ruoss

Cruz

et al. 2021

Sci Rep

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Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.Trial Registration This project is registered at clinicaltrials.gov under the name “Antibiotic ‘Dysbiosis’ in Preterm Infants” with trial number NCT02784821.

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Section: Resultsmentioning

confidence: 99%

“…Likewise, we summarize the types of antibiotics and the number of times antibiotics were prescribed by group (Supplementary Table S1). A full description of enrollment has been described previously 30 . There were no statistically significant adverse clinical events between the randomized groups.…”

Section: Resultsmentioning

confidence: 99%

Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

Russell

Ruoss

Cruz

et al. 2021

Sci Rep

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“… 62 This difference allows the effect of dispersal limitation on infant microbiome succession to be more closely examined in preterm infants, and a major finding of this study is that its influence exceeds habitat filtering. That could explain why studies of the effects of enteral feeding 20 , 58 and antibiotics 58 , 63 , 64 on health and microbiome composition have yielded somewhat inconsistent results for preterm infants, despite their known effects on the term infant microbiome.…”

Section: Discussionmentioning

confidence: 99%

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment

et al. 2021

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“…This difference allows the effect of dispersal limitation on infant microbiome succession to be more closely examined in preterm infants, and a major nding of this study is that its in uence exceeds habitat ltering. That could explain why studies on enteral feeding [23,76] and antibiotics [76,81,82] for their health bene ts and effects on microbiome composition have yielded somewhat inconsistent results for preterm infants, despite their known effects on the term infant microbiome.…”

Section: Discussionmentioning

confidence: 99%

Bacteroidota and Lachnospiraceae Integration Into the Gut Microbiome at Key Time Points in Early Life are Critical for Neurodevelopment

Oliphant

Ali

D’Souza

et al. 2021

Preprint

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Background: The early life microbiome plays critical roles in host development, shaping long-term outcomes including brain functioning. It is not known which initial infant colonizers elicit optimal neurodevelopment; thus, this study investigated the association between gut microbiome succession from the first week of life and head circumference growth (HCG), the earliest validated marker for neurodevelopment. Faecal samples were collected weekly from a preterm infant cohort during their neonatal intensive care unit stay and subjected to 16S rRNA gene sequencing for evaluating gut microbiome composition, in conjunction with clinical data and head circumference measurements. Results: Preterm infants with suboptimal HCG trajectories had a depletion in the abundance/prevalence of Bacteroidota and Lachnospiraceae, independent of morbidity and caloric restriction. The severity of gut microbiome depletion matched the timing of significant HCG pattern separation between study groups at 30 weeks postmenstrual age. Consideration of the clinical variables indicated that optimal infant microbiome succession is primarily driven by dispersal limitation (i.e., delivery mode) and secondarily by habitat filtering (i.e., antibiotics and enteral feeding). Conclusions: Bacteroidota and Lachnospiraceae are known core taxa of the adult microbiome, with roles in dietary glycan foraging, beneficial metabolite production and immunity, and our work provides strong evidence that their integration into the gut microbiome needs to occur early for optimal neurodevelopment.

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Routine Early Antibiotic Use in SymptOmatic Preterm Neonates: A Pilot Randomized Controlled Trial

Abstract: All rights reserved. No reuse allowed without permission.

Cited by 15 publications

References 24 publications

Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment

Bacteroidota and Lachnospiraceae Integration Into the Gut Microbiome at Key Time Points in Early Life are Critical for Neurodevelopment

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