Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):4870-4877. doi: 10.1080/14767058.2020.1869933. Epub 2021 Jan 5.
Indomethacin is an effective tocolytic to prevent extremely preterm birth. Prior studies have associated antenatal indomethacin exposure with adverse preterm neonatal intestinal and neurological outcomes. Indomethacin is a nephrotoxic medication that may also affect preterm neonatal kidneys. We sought to evaluate the effect of antenatal indomethacin on extremely preterm neonatal kidney function and acute kidney injury (AKI) in the first week of age. A retrospective cohort study was conducted on neonates born < 29 weeks at a level III neonatal intensive care unit (NICU) from January 2018-April 2019. Serum creatinine (sCr) values and urine output (UOP) in the first seven days of age and the neonate's peak serum creatinine within the first 30 days were evaluated. Neonatal AKI was defined by the modified neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition including urine output. 17 of the 55 neonates meeting criteria for this study were exposed to indomethacin. The average gestational age at birth was similar between study groups. Maternal preeclampsia was more common among women who did not receive indomethacin ( = 0.021). Indomethacin exposed neonates received more gentamicin ( = 0.024). Overall, staging of the neonatal AKI did not differ significantly between the study groups, regardless of how it was quantified (sCr or UOP) or the duration of time in which the injury developed (7 days or 30 days). Separate analysis of sCr and UOP in the first seven days also failed to show any statistically significant differences between the two groups. In this small cohort study of extremely preterm neonates, those born to mothers treated with indomethacin did not have an increased incidence of AKI compared to neonates born to unexposed mothers. Although no statistically significant differences in UOP or sCr were found, they deserve further evaluation in adequately powered prospective clinical trials. Future prospective studies with long-term follow-up utilizing advanced biomarkers are needed to determine how antenatal indomethacin affects extremely preterm neonatal kidney function in the NICU, during childhood, and as adults.
吲哚美辛是一种有效的保胎药物,可预防极早产儿早产。先前的研究表明,产前使用吲哚美辛与早产儿肠道和神经不良结局有关。吲哚美辛是一种肾毒性药物,也可能影响早产儿的肾脏。我们旨在评估产前吲哚美辛对出生于 29 周以下的极早产儿新生儿肾功能和生后第一周内急性肾损伤(AKI)的影响。对 2018 年 1 月至 2019 年 4 月在三级新生儿重症监护病房(NICU)出生的 < 29 周的新生儿进行了回顾性队列研究。评估了生后第 1 天至第 7 天的血清肌酐(sCr)值和尿量(UOP),以及生后第 30 天内新生儿的峰值 sCr。根据改良的新生儿肾脏病改善全球结局(KDIGO)定义,包括尿量,将新生儿 AKI 定义为 AKI。在符合本研究标准的 55 名新生儿中,有 17 名接受了吲哚美辛治疗。研究组间的平均出生胎龄相似。未接受吲哚美辛治疗的女性中,子痫前期更为常见(= 0.021)。接受吲哚美辛治疗的新生儿接受了更多的庆大霉素(= 0.024)。总体而言,无论如何定量(sCr 或 UOP)或损伤发展的时间(7 天或 30 天),两组间的新生儿 AKI 分期均无显著差异。对生后第 1 天的 sCr 和 UOP 的单独分析也未显示两组间存在任何统计学差异。在这项针对极早产儿的小队列研究中,与未暴露于母亲的新生儿相比,接受吲哚美辛治疗的母亲所生的新生儿 AKI 发生率没有增加。尽管 UOP 或 sCr 无统计学差异,但它们值得在充分的前瞻性临床试验中进一步评估。需要未来有前瞻性研究并进行长期随访,利用先进的生物标志物来确定产前吲哚美辛如何影响 NICU 中极早产儿的新生儿肾功能,以及在儿童期和成年期的肾功能。