Weller Brandi M, Shaddix Brittany Powers, Oschman Alexandra, Johnson Peter N, Neely Stephen B, Chaaban Hala, Williams Patricia K, Miller Jamie
J Pediatr Pharmacol Ther. 2021;26(5):455-459. doi: 10.5863/1551-6776-26.5.455. Epub 2021 Jun 28.
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.
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.
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.
No differences in neurodevelopmental outcomes were found between those with and without metronidazole exposure. Further studies are needed to validate our results.
甲硝唑被推荐作为新生儿坏死性小肠结肠炎（NEC）的一线治疗药物。已有甲硝唑相关神经毒性的报道，但尚未探讨其对新生儿长期神经发育的影响。主要目的是评估甲硝唑累积剂量与NEC新生儿贝利婴幼儿发展量表第三版（Bayley-III）各综合得分之间的关系。次要目的包括比较甲硝唑暴露组和非暴露组的癫痫发作率、平均Bayley-III得分，以及将Bayley-III三个综合得分中有两个≤79或一个得分≤70定义为神经发育障碍的情况。
这项多中心回顾性队列研究比较了2011年1月1日至2016年12月31日出生体重<1500克、发生2期或更严重NEC或自发性肠穿孔且在约1岁时在发育门诊接受随访的婴儿。如果婴儿出生后>72小时入院、有先天性神经发育异常、缺氧缺血性脑病、III或IV级脑室内出血或在NEC治疗前有癫痫发作，则将其排除。纳入的患者根据是否暴露于甲硝唑分为两组。使用SAS 9.4软件，采用描述性和推断性统计技术对数据进行评估。
共纳入41例患者。7例患者接受了甲硝唑治疗，34例患者在非甲硝唑组。两组之间唯一的统计学差异在于胎龄，非暴露组早产程度更高。两组之间在Bayley-III得分、癫痫发作率或神经发育障碍方面无统计学差异。
暴露于甲硝唑和未暴露于甲硝唑的患者在神经发育结局方面未发现差异。需要进一步研究来验证我们的结果。
