Absence of association between early antibiotic exposure and shortterm adverse outcomes in very preterm infants: a single-center retrospective study

Laura Fillistorf ¹ Giorgia Carra ^2,3 Raphaël Matusiak ^4,5 Varvara Dimopoulou ¹ Jérémie Despraz ³ Sylvain Meylan ² Eric Giannoni ^1*

• ¹ Clinic of Neonatology, Department Woman-Mother-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
• ² Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland
• ³ Biomedical Data Science Center, Department of Innovation and Clinical Research, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
• ⁴ Swiss Federal Institute of Technology Lausanne, Lausanne, Vaud, Switzerland
• ⁵ Swiss Data Science Center, Department of Computer Science, ETH Zurich, Zurich, Zürich, Switzerland

Antibiotics save lives but also carry significant risks, including increased antimicrobial resistance, higher healthcare costs, and disruption of the microbiome. However, the association between antibiotic exposure and short-term adverse outcomes remains uncertain. Our study aimed to evaluate whether early unnecessary antibiotic exposure in the first 7 days of life of very preterm infants is linked to shortterm adverse outcomes.This retrospective study included infants born below 32 weeks of gestation and hospitalized at the University Hospital of Lausanne between 01.01.2007 and 31.12.2022. Antibiotic exposure was quantified during the first seven postnatal days by the median number of days of antibiotics. Multilinear regressions and mixed effect models analyzed the association between the number of days of antibiotics and death, late-onset sepsis, necrotizing enterocolitis, severe bronchopulmonary dysplasia, severe retinopathy of prematurity and cystic periventricular leukomalacia. The primary outcome was a composite of at least one of the listed adverse outcomes, while the secondary outcomes consisted of each adverse outcome individually. Adjusted odds ratio (aOR) and p-value were calculated.We included 1398 preterm infants. The median gestational age was 29 weeks (IQR 27-30) and the median birthweight was 1144 grams (820-1420). The median number of days of antibiotics declined by 53%, from 4 days in 2007 to 1.9 days in 2022 (p < 0.0001). The number of days of antibiotics was not associated with the composite outcome (aOR 0.97 [0.82-1.17], p = 0.80, adjusted p = 0.80) or any of the following adverse outcomes: mortality (aOR 1.10 [0.78-1.55], p = 0.58, adjusted p = 0.69), lateonset sepsis (aOR 0.74 [0.59-0.93], p = 0.01, adjusted p = 0.07), necrotizing enterocolitis ], p = 0.26, adjusted p = 0.65), severe bronchopulmonary dysplasia (aOR 1.12 [0.88 -1.42], p = 0.36, adjusted p = 0.65), severe retinopathy of prematurity ], p = 0.43, adjusted p = 0.65), and cystic periventricular leukomalacia (aOR 1.02 [0.69-1.99], p = 0.91, adjusted p = 0.91).We found no association between early antibiotic exposure and short-term adverse outcomes.