High cumulative antibiotic exposure in extremely low birth weight infants during the first month of life: Risk factors and clinical outcomes.

Background: Extremely low birthweight (ELBW) infants invariably receive multiple antibiotic therapies during hospitalization. However, the causes of high cumulative antibiotic exposure, as well as the impact of such exposure on the outcomes of preterm infants, particularly long-term neurodevelopmental outcomes, remain to be elucidated. Furthermore, the cumulative effects of simultaneous use of multiple antibiotics are often overlooked.

Methods: We included ELBW infants born between January 1, 2016, and December 31, 2020. The duration of antibiotic therapy was calculated as Days of Therapy (DOT), with each antibiotic administered during the first month of life added cumulatively. The infants were divided into two groups: the low cumulative antibiotic exposure group and the high cumulative antibiotic exposure group.

Results: Of 453 eligible ELBW infants, 358 met the inclusion criteria. Multivariable logistic regression indicated a low birthweight [adjusted odds ratio (aOR) 0.996, 95% confidence interval (CI) 0.994, 0.998], chorioamnionitis (aOR 2.195, 95% CI 1.145, 4.210), sepsis (aOR 2.538, 95% CI 1.417, 4.544), and necrotizing enterocolitis (aOR 11.798, 95% CI 2.637, 52.784) as independent factors associated with high cumulative antibiotic exposure. These infants were associated with poor short-term outcomes, including mortality (aOR 9.031, 95% CI 2.433, 33.448), moderate to severe bronchopulmonary dysplasia (aOR 2.895, 95% CI 1.471, 5.699), and retinopathy of prematurity necessitating therapy (aOR 2.503, 95% CI 1.363, 4.597). Although infants in the low cumulative antibiotic exposure group had higher neurodevelopmental scores across all three BSID-III domains at each corrected age compared to those in the high cumulative antibiotic exposure group, the cumulative antibiotic exposure did not significantly influence the score changes in the linear mixed-effects models.

Conclusions: High cumulative antibiotic exposure in early life is associated with adverse short-term outcomes in ELBW infants. The impacts on long-term neurodevelopmental require further investigation. When prescribing antibiotics to infants, caution should be exercised to avoid unnecessary exposure.