Division of Neonatology and Newborn Medicine, Department of Pediatrics, and.
Harvard Neonatal-Perinatal Medicine Fellowship Training Program, Boston, Massachusetts.
Pediatrics. 2021 Feb;147(2). doi: 10.1542/peds.2019-3202.
The most common cause of persistent hypoglycemia in the neonatal period is hyperinsulinism. Severe, refractory hypoglycemia resulting from hyperinsulinism can lead to significant brain injury and permanent cognitive disability. Diazoxide is the first-line and only US Food and Drug Administration-approved, pharmacologic treatment for refractory hyperinsulinism. In recent years, the use of diazoxide in neonates with persistent hyperinsulinemic hypoglycemia has increased in the United States. Known adverse effects of diazoxide include fluid retention, hypertrichosis, neutropenia, thrombocytopenia, and more recently, pulmonary hypertension. It is currently unknown if diazoxide exposure is associated with an increased risk of necrotizing enterocolitis (NEC) in neonates. We reviewed the cases of 24 patients in a level IV NICU at Massachusetts General Hospital who received diazoxide over 12 years (April 2006-April 2018). All 24 patients received enteral diazoxide for refractory hyperinsulinemic hypoglycemia. A total of 5 patients developed NEC after initiation of diazoxide based on clinical and radiographic findings, corresponding to 20% of infants exposed to diazoxide. This is above our baseline incidence of NEC (1% for all inborn infants and 6% for all inborn very low birth weight infants). More research and monitoring are necessary to characterize the potential risk of NEC associated with the use of diazoxide in the neonatal period.
新生儿期持续性低血糖最常见的原因是胰岛素过多症。严重的、难治性的胰岛素过多症引起的低血糖可导致严重的脑损伤和永久性认知障碍。二氮嗪是治疗难治性胰岛素过多症的一线药物,也是唯一获得美国食品和药物管理局批准的药物。近年来,美国使用二氮嗪治疗持续性高胰岛素血症性低血糖的新生儿的情况有所增加。二氮嗪已知的不良反应包括液体潴留、多毛症、中性粒细胞减少症、血小板减少症,最近还有肺动脉高压。目前尚不清楚二氮嗪暴露是否会增加新生儿坏死性小肠结肠炎(NEC)的风险。我们回顾了马萨诸塞州综合医院四级 NICU 12 年来(2006 年 4 月至 2018 年 4 月)接受二氮嗪治疗的 24 例患者的病例。所有 24 例患者均因难治性高胰岛素血症性低血糖接受肠内二氮嗪治疗。根据临床和影像学发现,共有 5 例患者在开始使用二氮嗪后发生 NEC,占接受二氮嗪治疗的婴儿的 20%。这高于我们的 NEC 基线发生率(所有足月儿的 1%和所有极低出生体重儿的 6%)。需要进一步的研究和监测,以明确新生儿期使用二氮嗪与 NEC 相关的潜在风险。