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Abstract：
BACKGROUND: With a wide therapeutic index, efficacy, ease of use, and other neuroprotective and respiratory benefits, caffeine citrate(CC) is currently the drug of choice for preterm neonates (PTNs). Caffeine-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side-effects (CC-APSEs) result in lower daily-weight gain (WG) in premature neonates. This study aimed to evaluate the risk factors for daily-WG in neonates exposed to different dose regimens of caffeine in ICU.
METHODS: This retrospective cohort study included neonates of ≤ 36weeks gestational age (GA) and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I (received; standard-doses = 5 mg/kg/day), group-II (received;>5-7 mg/kg/day), and group-III (received;>7 mg/kg/day). Prenatal and postnatal clinical characteristics, CC-regimen, daily-WG, CC-APSEs, and concomitant risk-factors, including daily-caloric intake, Parenteral-Nutrition duration, steroids, diuretics, and ibuprofen exposure, were analyzed separately for group-II and group-III using group-I as standard. Regression analysis was performed to evaluate the risk factors for daily-WG.
RESULTS: Included 314 PTNs. During 15-28 DOL, the mean-daily-WG(MD-WG) was significantly higher in group-I than group-II [19.9 ± 0.70 g/kg/d vs. 17.7 ± 0.52 p = 0.036] and group-III [19.9 ± 0.70 g/kg/d vs. 16.8 ± 0.73 p < 0.001]. During 29-42 DOL the MD-WG of group-I was only significantly higher than group-III [21.7 ± 0.44 g/kg/d vs. 18.3 ± 0.41 g/kg/d p = 0.003] and comparable with group-II. During 15-28 DOL, observed CC-APSEs was significantly higher in group-II and III but during 29-42 DOL it was only significant in group-III. In the adjusted regression analysis for daily-WG during 15-28DOL, with respect to standard-dose, 5-7 mg/kg/day (β=-1.04; 95%CI:-1.62,-0.93) and > 7-10 mg/kg/day (β=-1.36; 95%CI:-1.56,-1.02) were associated with a lower daily-WG. However, during 29-42DOL, this association was present only for > 7-10 mg/kg/day (β=-1.54; 95%CI:-1.66,-1.42). The GA ≤ 27weeks (β=-1.03 95%CI:-1.24, -0.88) was associated with lower daily-WG only during 15-28DOL. During both periods of therapy, higher cumulative-caffeine dose and presence of culture proven sepsis, tachypnea, hyponatremia, and feeding intolerance were significantly associated with lower daily-WG. Conversely, daily kcal intake was found to be linked with an increase in daily-WG in both periods.
CONCLUSIONS: In this study cohort exposure to higher caffeine daily and cumulative doses is associated with lower postnatal daily-WG in PTNs than standard-daily doses, which may be due to its catabolic effects and CC-APSEs.
METHODS: This retrospective cohort study included neonates of ≤ 36weeks gestational age (GA) and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I (received; standard-doses = 5 mg/kg/day), group-II (received;>5-7 mg/kg/day), and group-III (received;>7 mg/kg/day). Prenatal and postnatal clinical characteristics, CC-regimen, daily-WG, CC-APSEs, and concomitant risk-factors, including daily-caloric intake, Parenteral-Nutrition duration, steroids, diuretics, and ibuprofen exposure, were analyzed separately for group-II and group-III using group-I as standard. Regression analysis was performed to evaluate the risk factors for daily-WG.
RESULTS: Included 314 PTNs. During 15-28 DOL, the mean-daily-WG(MD-WG) was significantly higher in group-I than group-II [19.9 ± 0.70 g/kg/d vs. 17.7 ± 0.52 p = 0.036] and group-III [19.9 ± 0.70 g/kg/d vs. 16.8 ± 0.73 p < 0.001]. During 29-42 DOL the MD-WG of group-I was only significantly higher than group-III [21.7 ± 0.44 g/kg/d vs. 18.3 ± 0.41 g/kg/d p = 0.003] and comparable with group-II. During 15-28 DOL, observed CC-APSEs was significantly higher in group-II and III but during 29-42 DOL it was only significant in group-III. In the adjusted regression analysis for daily-WG during 15-28DOL, with respect to standard-dose, 5-7 mg/kg/day (β=-1.04; 95%CI:-1.62,-0.93) and > 7-10 mg/kg/day (β=-1.36; 95%CI:-1.56,-1.02) were associated with a lower daily-WG. However, during 29-42DOL, this association was present only for > 7-10 mg/kg/day (β=-1.54; 95%CI:-1.66,-1.42). The GA ≤ 27weeks (β=-1.03 95%CI:-1.24, -0.88) was associated with lower daily-WG only during 15-28DOL. During both periods of therapy, higher cumulative-caffeine dose and presence of culture proven sepsis, tachypnea, hyponatremia, and feeding intolerance were significantly associated with lower daily-WG. Conversely, daily kcal intake was found to be linked with an increase in daily-WG in both periods.
CONCLUSIONS: In this study cohort exposure to higher caffeine daily and cumulative doses is associated with lower postnatal daily-WG in PTNs than standard-daily doses, which may be due to its catabolic effects and CC-APSEs.
摘要：
背景：具有广泛的治疗指数，功效,易用性,以及其他神经保护和呼吸益处，柠檬酸咖啡因（CC）目前是早产新生儿（PTN）的首选药物。咖啡因引起的过度能量消耗，利尿,利钠尿,和其他CC相关的潜在副作用（CC-APSE）导致早产儿的日体重增加（WG）降低。本研究旨在评估ICU中暴露于不同剂量咖啡因方案的新生儿每日WG的危险因素。
方法：这项回顾性队列研究包括胎龄≤36周且接受CC治疗的新生儿。对相同的参与者进行了两个出生后阶段的数据分析：15-28天和29-42天的生命（DOL）。根据每日CC剂量，形成的I组（接受；标准剂量=5mg/kg/天），II组（接受；>5-7mg/kg/天），和组-III(接受;>7mg/kg/天)。产前和产后临床特征，CC-方案，daily-WG,CC-APSE,以及伴随的风险因素，包括每日热量摄入，胃肠外营养持续时间,类固醇,利尿剂,和布洛芬接触,以I组为标准，分别对II组和III组进行分析。进行回归分析以评估每日WG的危险因素。
结果：包括314个PTN。在15-28DOL期间，I组的平均每日WG（MD-WG）明显高于II组[19.9±0.70g/kg/dvs.17.7±0.52p=0.036]和III组[19.9±0.70g/kg/dvs.16.8±0.73p<0.001]。在29-42DOL期间，I组的MD-WG仅明显高于III组[21.7±0.44g/kg/dvs.18.3±0.41g/kg/dp=0.003]，与II组相当。在15-28DOL期间，观察到的CC-APSE在II组和III组中显着更高，但在29-42DOL期间，仅在III组中显着。在15-28DOL期间每日WG的调整回归分析中，关于标准剂量，5-7mg/kg/天（β=-1.04；95CI：-1.62，-0.93）和>7-10mg/kg/天（β=-1.36；95CI：-1.56，-1.02）与较低的每日WG相关。然而,在29-42DOL期间，这种关联仅在>7-10mg/kg/d时存在(β=-1.54;95CI:-1.66,-1.42).仅在15-28DOL期间，GA≤27周（β=-1.0395CI：-1.24，-0.88）与较低的日WG相关。在这两个治疗期间，较高的累积咖啡因剂量和培养证实的败血症的存在，呼吸急促,低钠血症,喂养不耐受与每日WG降低显著相关。相反，发现两个时期的每日千卡摄入量与每日WG的增加有关。
结论：在这项研究中，每日和累积剂量较高的咖啡因暴露与PTNs的产后每日WG低于标准每日剂量相关。这可能是由于其分解代谢效应和CC-APSE。
方法：这项回顾性队列研究包括胎龄≤36周且接受CC治疗的新生儿。对相同的参与者进行了两个出生后阶段的数据分析：15-28天和29-42天的生命（DOL）。根据每日CC剂量，形成的I组（接受；标准剂量=5mg/kg/天），II组（接受；>5-7mg/kg/天），和组-III(接受;>7mg/kg/天)。产前和产后临床特征，CC-方案，daily-WG,CC-APSE,以及伴随的风险因素，包括每日热量摄入，胃肠外营养持续时间,类固醇,利尿剂,和布洛芬接触,以I组为标准，分别对II组和III组进行分析。进行回归分析以评估每日WG的危险因素。
结果：包括314个PTN。在15-28DOL期间，I组的平均每日WG（MD-WG）明显高于II组[19.9±0.70g/kg/dvs.17.7±0.52p=0.036]和III组[19.9±0.70g/kg/dvs.16.8±0.73p<0.001]。在29-42DOL期间，I组的MD-WG仅明显高于III组[21.7±0.44g/kg/dvs.18.3±0.41g/kg/dp=0.003]，与II组相当。在15-28DOL期间，观察到的CC-APSE在II组和III组中显着更高，但在29-42DOL期间，仅在III组中显着。在15-28DOL期间每日WG的调整回归分析中，关于标准剂量，5-7mg/kg/天（β=-1.04；95CI：-1.62，-0.93）和>7-10mg/kg/天（β=-1.36；95CI：-1.56，-1.02）与较低的每日WG相关。然而,在29-42DOL期间，这种关联仅在>7-10mg/kg/d时存在(β=-1.54;95CI:-1.66,-1.42).仅在15-28DOL期间，GA≤27周（β=-1.0395CI：-1.24，-0.88）与较低的日WG相关。在这两个治疗期间，较高的累积咖啡因剂量和培养证实的败血症的存在，呼吸急促,低钠血症,喂养不耐受与每日WG降低显著相关。相反，发现两个时期的每日千卡摄入量与每日WG的增加有关。
结论：在这项研究中，每日和累积剂量较高的咖啡因暴露与PTNs的产后每日WG低于标准每日剂量相关。这可能是由于其分解代谢效应和CC-APSE。
