Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study

Letouzey, Mathilde; Lorthe, Elsa; Marchand-Martin, Laetitia; Kayem, Gilles; Charlier, Caroline; Butin, Marine; Mitha, Ayoub; Kaminski, Monique; Benhammou, Valérie; Ancel, Pierre Yves; Boileau, Pascal; Foix‐L’Hélias, L.

doi:10.1016/j.jpeds.2021.11.075

Cited by 15 publications

(7 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Registration was discontinued after the 28 th day of life, which could have led to missing some LOS cases. As the first LOS episode usually occurs within the first weeks of life, we hypothesized that the number of missed cases would be limited [35].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

et al. 2022

View full text Add to dashboard Cite

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics’ effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age < 30 weeks) born in 9 centers in the Netherlands and Belgium between Oct. 2014 and Jan. 2019. EEAE association with NEC and LOS development was analyzed by multivariate regression. After excluding 56 EOS cases, 1259 infants were included. A total of 1122 infants (89.1%) were exposed to empirical antibiotics for the suspicion of EOS of whom 802 (63.7%) had short (≤ 72 h) and 320 (25.4%) prolonged EEAE (> 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19–0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35–0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85–0.97]; p = 0.003).Conclusion: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored. What is Known:• Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis.• The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated. What is New:• Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged.• A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life.

show abstract

Section: Discussion/conclusionmentioning

confidence: 99%

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, recent observational data from 13 Neonatal Intensive Care Units (NICUs) from 5 continents (n=2831) identified that NEC incidence was higher in infants who did not receive empirical antibiotics early after birth, despite higher gestational age, compared with those receiving them (OR: 1.8 (95% CI 1.1 to 2.9)), with even higher OR when adjusted for relevant confounders (OR: 4.0 (95% CI 2.1 to 7.3)) 10. In contrast, results from a very recent study in preterm infants with low risk of infection shows opposite trends of lower odds in those not treated, but is underpowered for NEC as outcome (n=641, OR: 0.7 (95% CI 0.3 to 1.5)) 11. There is an increasing focus on antibiotic stewardship, and it can be expected that the proportion of infants that are not given antibiotics after preterm birth will increase in the coming years.…”

Section: Introductionmentioning

confidence: 93%

“… 10 In contrast, results from a very recent study in preterm infants with low risk of infection shows opposite trends of lower odds in those not treated, but is underpowered for NEC as outcome (n=641, OR: 0.7 (95% CI 0.3 to 1.5)). 11 There is an increasing focus on antibiotic stewardship, and it can be expected that the proportion of infants that are not given antibiotics after preterm birth will increase in the coming years. Therefore, it is important to know if lower early usage of antibiotics will increase the incidence of NEC.…”

Section: Introductionmentioning

confidence: 99%

Early antibiotic use and incidence of necrotising enterocolitis in very preterm infants: a protocol for a UK based observational study using routinely recorded data

et al. 2022

View full text Add to dashboard Cite

IntroductionNecrotising enterocolitis (NEC) remains a major contributor to preterm mortality and morbidity. Prolonged duration of antibiotic therapy after delivery is associated with later NEC development but recent evidence suggests that absence of antibiotic treatment after delivery may also increase NEC risk. We will explore this controversy using a large pre-existing dataset of preterm infants in the UK.Methods and analysisThis is a retrospective cohort study using data from UK National Neonatal Research Database (NNRD) for infants born 1 January 2012 to 31 December 2020. Eligible infants will be <32 weeks gestation, alive on day 3. Primary outcome is development of severe NEC, compared in infants receiving early antibiotics (days 1–2 after birth) and those not. Subgroup analysis on duration of early antibiotic exposure will also occur. Secondary outcomes are: late onset sepsis, total antibiotic use, predischarge mortality, retinopathy of prematurity, intraventricular haemorrhage, bronchopulmonary dysplasia, focal intestinal perforation and any abdominal surgery. To address competing risks, incidence of death before day 7, 14 and 28 will be analysed. We will perform logistic regression and propensity score matched analyses. Statistical analyses will be guided by NEC risk factors, exposures and outcome presented in a causal diagram. These covariates include but are not limited to gestational age, birth weight, small for gestational age, sex, ethnicity, delivery mode, delivery without labour, Apgar score, early feeding and probiotic use. Sensitivity analyses of alternate NEC definitions, specific antibiotics and time of initiation will occur.Ethics and disseminationWe will use deidentified data from NNRD, which holds permissions for the original data, from which parents can opt out and seek study-specific research ethics approval. The results will help to determine optimal use of early antibiotics for very preterm infants.ImplicationsThis data will help optimise early antibiotic use in preterm infants.Trial registration numberISRCTN55101779.

show abstract

“…I read with interest the report by Letouzey et al describing the effects of early exposure to antibiotics in infants born very preterm at low risk for early-onset sepsis. 1 They found no association between the early exposure to antibiotics with death, late-onset sepsis, and/or necrotizing enterocolitis. However, they reported an association with a greater risk of severe cerebral lesions and moderate-to-severe bronchopulmonary dysplasia.…”

mentioning

confidence: 95%

Association between the early use of antibiotics in infants born preterm and severe cerebral lesions and moderate-to-severe bronchopulmonary dysplasia

Manzar

2022

The Journal of Pediatrics

View full text Add to dashboard Cite

Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study

Cited by 15 publications

References 35 publications

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

Early antibiotic use and incidence of necrotising enterocolitis in very preterm infants: a protocol for a UK based observational study using routinely recorded data

Association between the early use of antibiotics in infants born preterm and severe cerebral lesions and moderate-to-severe bronchopulmonary dysplasia

Contact Info

Product

Resources

About