早产儿咖啡因治疗方案与早产儿骨质疏松症的关系：一项队列回顾性研究。

Relationship of caffeine regimen with osteopenia of prematurity in preterm neonates: a cohort retrospective study.

机构信息

Department of Paediatrics & Child Health, Aga Khan University, Karachi, Pakistan.

Department of Neonatology & Paediatrics, Dow University of Health Sciences, Karachi, Pakistan.

出版信息

BMC Pediatr. 2022 Jul 21;22(1):437. doi: 10.1186/s12887-022-03493-x.

DOI:10.1186/s12887-022-03493-x

PMID:35864501

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9306044/

Abstract

BACKGROUND

Caffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. Caffeine-induced excessive calcium loss can promote the development of metabolic bone disease (MBD) in preterm neonates. This study aimed to evaluate the effect of the caffeine regimen on the development of osteopenia of prematurity (OOP), using serum alkaline phosphatase (serum-ALP) concentrations as a surrogate marker at the 4 week of life.

METHODS

This retrospective cohort study was conducted including neonates of < 32 weeks gestational age (GA) and birth weight < 1500 g, admitted to NICU from April-2017 to December-2018 and received caffeine therapy till 28 days of life for AOP. Based on serum-ALP levels, formed the high and low-ALP groups. Neonatal characteristics, caffeine regimen, risk factors for OOP, including duration of parenteral nutrition (PN), exposure to medicines associated with MBD, and intake of essential vitamins and minerals, were compared in both groups. Predictors of OOP were analyzed through logistic regression.

RESULTS

From the total of 268 participants, 52 (19%) developed OOP, mostly female (61.5%). In the high ALP group, the serum-ALP levels were significantly higher than in the low-ALP group (725.0 ± 143.8 vs 273.6 ± 55.0 units/L, p < 0.001). The high-ALP group received significantly (p < 0.001) higher daily and cumulative caffeine doses and were associated with a higher likelihood of developing OOP in this study cohort [cumulative dose (mg) (AOR = 1.082 95% CI 1.011 to 1.157) and daily dose (mg/kg/day) (AOR = 2.892 95% CI 1.392 to 6.007)]. Smaller GA was found directly related to OOP. Among the other medical risk factors, phosphorus intake was significantly low in the high-ALP group. No, significant relationship between duration of PN and use of steroids and diuretics, and intake of vitamins and minerals were identified.

CONCLUSION

The daily and cumulative doses of caffeine and smaller GA are associated with the development of OOP in this study cohort. Clinical randomized control studies are needed to validate the outcomes and determine the range of safest and most effective caffeine doses for treating AOP in preterm neonates.

摘要

背景

咖啡因是新生儿重症监护病房（NICU）中常规使用的药理学活性化合物，用于治疗早产儿呼吸暂停（AOP），还可以降低早产儿支气管肺发育不良和脑瘫的风险。咖啡因引起的钙过度流失会促进早产儿代谢性骨病（MBD）的发展。本研究旨在评估咖啡因方案对早产儿骨质疏松症（OOP）发展的影响，以生后 4 周的血清碱性磷酸酶（血清-ALP）浓度作为替代标志物。

方法

这是一项回顾性队列研究，纳入了 2017 年 4 月至 2018 年 12 月期间胎龄（GA）<32 周和出生体重<1500g 的入住 NICU 的新生儿，接受咖啡因治疗以治疗 AOP，直至 28 天。根据血清-ALP 水平，分为高和低-ALP 组。比较两组新生儿特征、咖啡因方案、OOP 的危险因素，包括肠外营养（PN）持续时间、与 MBD 相关的药物暴露以及必需维生素和矿物质的摄入。通过逻辑回归分析 OOP 的预测因素。

结果

在 268 名参与者中，52 名（19%）发生了 OOP，主要为女性（61.5%）。在高 ALP 组中，血清-ALP 水平明显高于低-ALP 组（725.0±143.8比 273.6±55.0单位/L，p<0.001）。高 ALP 组接受的每日和累积咖啡因剂量明显更高（p<0.001），且在本研究队列中更有可能发生 OOP[累积剂量（mg）（AOR=1.082，95%CI 1.011-1.157）和每日剂量（mg/kg/天）（AOR=2.892，95%CI 1.392-6.007)]。GA 越小，与 OOP 直接相关。在其他医学危险因素中，高 ALP 组的磷摄入量明显较低。未发现 PN 持续时间、使用皮质类固醇和利尿剂以及维生素和矿物质摄入与 OOP 之间存在显著关系。