Antibiotics Use and Its Effects on the Establishment of Feeding Tolerance in Preterm Neonates

Abstract

Objective Antibiotics are one of the most widely used medications in today's neonatal intensive care units. Indiscriminate antibiotic usage persists in preterm newborns who are symptomatic due to factors linked to prematurity rather than being septic. Previous studies in older infants suggest that prior antibiotic administration is associated with possible dysmotility and microbial dysbiosis in the intestinal tract. We hypothesize that early antibiotic administration impacts high-risk preterm infants' tolerance to enteral feeding advancement.

Study Design As part of the Routine Early Antibiotic Use in SymptOmatic Preterm Neonates study, symptomatic preterm newborns without maternal infection risk factors were randomized to receive or not receive antibiotics, with C1 receiving antibiotics and C2 not. Of the 55 newborns that underwent pragmatic randomization, 28 preterm neonates in group C1 received antibiotics.

Results The premature neonates in the randomized groups who received antibiotics and those who did not showed no differences in sustained feeding tolerance.

Conclusion Our investigation of the risk of feeding issues in babies who get antibiotics early in life revealed no differences between neonates who received antibiotics and those who did not when the randomized controlled trial data alone was reviewed. Given the sample sizes, it is uncertain if the preceding analysis is powerful enough to detect differences (a significant percentage of neonates who were randomly assigned to NOT get antibiotics subsequently received early treatment due to changing clinical conditions). This affirms the requirement for a meticulously designed prospective randomized study.

Key Points

• Defining feeding tolerance for the first time in neonates.

• Patients from the REASON trial were evaluated.

• Preterm neonates were the focus of this study.

Keywords

REASON trial - feeding intolerance definition - prematurity - antibiotic use - neonatal microbiome

Authors' Contributions

The study design of this retrospective chart review to study feeding intolerance was contributed by all authors. The clinical data were extracted by Neel Singh and Will Lester. The statistical analysis of clinical data was assisted by S.A. and M.G. The results and the preparation of this publication were evaluated by all the authors.

Publikationsverlauf

Eingereicht: 08. Mai 2023

Angenommen: 06. Juni 2023

Accepted Manuscript online:
12. Juni 2023

Artikel online veröffentlicht:
20. Juli 2023

• References

• 1 Mackie RI, Sghir A, Gaskins HR. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 1999; 69 (05) 1035S-1045S
• 2 Heijtz RD. Fetal, neonatal, and infant microbiome: perturbations and subsequent effects on brain development and behavior. Semin Fetal Neonatal Med 2016; 21 (06) 410-417
• 3 Chong CYL, Bloomfield FH, O'Sullivan JM. Factors affecting gastrointestinal microbiome development in neonates. Nutrients 2018; 10 (03) 274
• 4 Schwartz DJ, Langdon AE, Dantas G. Understanding the impact of antibiotic perturbation on the human microbiome. Genome Med 2020; 12 (01) 82
• 5 Ruoss JL, Bazacliu C, Russell JT. et al. Routine early antibiotic use in symptomatic preterm neonates: a pilot randomized controlled trial. J Pediatr 2021; 229: 294-298.e3
• 6 Russell JT, Lauren Ruoss J, de la Cruz D. et al. Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants. Sci Rep 2021; 11 (01) 1943
• 7 Patton L, Li N, Garrett TJ. et al. Antibiotics effects on the fecal metabolome in preterm infants. Metabolites 2020; 10 (08) 331
• 8 Korpela K, Renko M, Paalanne N. et al. Microbiome of the first stool after birth and infantile colic. Pediatr Res 2020; 88 (05) 776-783
• 9 Cotten CM, Taylor S, Stoll B. et al; NICHD Neonatal Research Network. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123 (01) 58-66
• 10 McCallie KR, Lee HC, Mayer O, Cohen RS, Hintz SR, Rhine WD. Improved outcomes with a standardized feeding protocol for very low birth weight infants. J Perinatol 2011; 31 (Suppl. 01) S61-S67
• 11 Calkins KL, Venick RS, Devaskar SU. Complications associated with parenteral nutrition in the neonate. Clin Perinatol 2014; 41 (02) 331-345
• 12 Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics 2005; 116 (03) 595-602
• 13 Tripathi N, Cotten CM, Smith PB. Antibiotic use and misuse in the neonatal intensive care unit. Clin Perinatol 2012; 39 (01) 61-68
• 14 Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol 2011; 31 (Suppl. 01) S29-S34
• 15 Martinez FE, Ferri WAG, Leone CR. et al; for Brazilian Neonatal Research Network. Early empiric antibiotic use is associated with delayed feeding tolerance in preterm infants: a retrospective analysis. J Pediatr Gastroenterol Nutr 2017; 65 (01) 107-110