A Pilot Evaluation of the Possible Association of Metronidazole With Neurodevelopmental Outcomes in Premature Neonates.

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DOI: 10.5863/1551-6776-26.5.455; PMCID: PMC8244961


OBJECTIVE: Metronidazole is recommended as a first-line treatment of necrotizing enterocolitis (NEC) in neonates. Metronidazole-associated neurotoxicity has been reported, but long-term neurodevelopmental effects in neonates have not been explored. The primary objective was to evaluate the relationship of cumulative metronidazole dose with each Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) composite score in neonates with NEC. Secondary objectives included comparison of seizure rates, mean Bayley-III scores, and neurodevelopmental impairment defined as 2 of 3 Bayley-III composite scores ≤ 79 or 1 score ≤ 70 between the metronidazole exposed and non-exposed groups.

METHODS: This multisite, retrospective cohort study compared infants with a birth weight < 1500 grams between January 1, 2011, and December 31, 2016, who developed stage 2 or greater NEC or spontaneous intestinal perforation and were followed up at a developmental clinic visit at approximately 1 year of age. Patients were excluded if admitted >72 hours of life, had congenital neurodevelopmental anomalies, hypoxic ischemic encephalopathy, grade III or IV intraventricular hemorrhage, or seizures prior to treatment of NEC. Included patients were stratified into 2 groups based on metronidazole exposure versus no metronidazole. Data were assessed using descriptive and inferential statistical techniques, using SAS 9.4.

RESULTS: Forty-one patients were included. Seven patients received metronidazole and 34 patients were in the non-metronidazole group. The only statistical difference noted between groups was for gestational age, with the non-exposed group being more premature. There was no statistical difference in Bayley-III scores, seizure rates, or neurodevelopmental impairment between groups.

CONCLUSION: No differences in neurodevelopmental outcomes were found between those with and without metronidazole exposure. Further studies are needed to validate our results.

Journal Title

J Pediatr Pharmacol Ther





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adverse drug effect; metronidazole; necrotizing enterocolitis; neurodevelopment; neurotoxicity; preterm

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