Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden.
Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
JAMA Netw Open. 2021 May 3;4(5):e217269. doi: 10.1001/jamanetworkopen.2021.7269.
While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework.
To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks).
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used registry data for 97 377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020.
Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS.
In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic corticosteroids for lung disease, treatment with supplemental oxygen at 28 days' postnatal age and at 36 weeks' postmenstrual age. Odds ratios (ORs) were calculated and adjusted for any prenatal corticosteroid treatment, cesarean delivery, GA, infant sex, Apgar score at 10 minutes, and birth weight z score of less than -2.
In total, 7980 surfactant administrations were given to 5209 infants (2233 [42.9%] girls; 2976 [57.1%] boys): 629 (12.1%) born at full term, 691 (13.3%) at 32 to 36 weeks' GA, 1544 (29.6%) at 28 to 31 weeks' GA, and 2345 (45.0%) at less than 28 weeks' GA. Overall, 977 infants (18.8%) received off-label use. In 1364 of 3508 infants (38.9%) with GA of 22 to 31 weeks, the first administration of surfactant was given more than 2 hours after birth, and this was associated with higher odds of pneumothorax (adjusted OR [aOR], 2.59; 95% CI, 1.76-3.83), intraventricular hemorrhage grades 3 to 4 (aOR, 1.71; 95% CI, 1.23-2.39), receipt of postnatal corticosteroids (aOR, 1.57; 95% CI, 1.22-2.03), and longer duration of assisted ventilation (aOR, 1.34; 95% CI, 1.04-1.72) but also higher survival (aOR, 1.45; 95% CI, 1.10-1.91) than among infants treated within 2 hours of birth. In 146 infants (2.8%), the recommended maximum of 3 surfactant administrations was exceeded but without associated improvements in outcome. Omission of surfactant treatment occurred in 203 of 3551 infants (5.7%) who were receiving mechanical ventilation and was associated with lower survival (aOR, 0.49; 95% CI, 0.30-0.82). In full-term infants, 336 (53.4%) of those receiving surfactant had a diagnosis of meconium aspiration syndrome. Surfactant for meconium aspiration was not associated with improved neonatal outcomes.
In this study, adherence to best practices and labels for surfactant use in newborn infants varied, with important clinical implications for neonatal outcomes.
虽然临床试验已经评估了表面活性剂治疗呼吸窘迫综合征（RDS）的效果，但对于表面活性剂在这种框架之外的使用方式知之甚少。
评估胎龄（GA）和结局之间的表面活性剂注册使用、超说明书使用和遗漏使用的情况，主要针对极早产儿（GA<32 周）。
设计、地点和参与者：本基于人群的队列研究使用了瑞典 2009 年至 2018 年间出生的 97377 名婴儿的登记数据。婴儿无畸形且需要新生儿护理。数据分析于 2019 年 6 月至 2020 年 6 月进行。
表面活性剂给药的时间和次数、超说明书使用和遗漏使用。注册使用由药物标签定义（RDS 用 1-3 次给药）。遗漏使用是指尽管有 RDS 机械通气，但仍未给予表面活性剂。
院内生存率、气胸、脑室出血 3-4 级、机械通气持续时间、肺疾病时使用的产后全身皮质类固醇、28 天和 36 周龄时补充氧气的治疗。计算了比值比（ORs），并调整了任何产前皮质类固醇治疗、剖宫产、GA、婴儿性别、10 分钟时的 Apgar 评分和出生体重 z 评分小于-2 的因素。
共给予 7980 次表面活性剂治疗 5209 名婴儿（2233[42.9%]名女孩；2976[57.1%]名男孩）：629 名（12.1%）足月出生，691 名（13.3%）GA 为 32 至 36 周，1544 名（29.6%）GA 为 28 至 31 周，2345 名（45.0%）GA 小于 28 周。总体而言，977 名婴儿（18.8%）接受了超说明书使用。在 3508 名 22 至 31 周 GA 的婴儿中，1364 名（38.9%）婴儿的第一次表面活性剂治疗在出生后 2 小时以上给予，这与气胸（调整比值比[aOR]，2.59；95%置信区间[CI]，1.76-3.83）、脑室出血 3-4 级（aOR，1.71；95%CI，1.23-2.39）、接受产后皮质类固醇（aOR，1.57；95%CI，1.22-2.03）和更长时间的辅助通气（aOR，1.34；95%CI，1.04-1.72）的几率较高相关，但也与生存率（aOR，1.45；95%CI，1.10-1.91）较高相关，而在出生后 2 小时内接受治疗的婴儿则较低。在 146 名婴儿（2.8%）中，超过了推荐的最大 3 次表面活性剂给药次数，但与结局的改善无关。在接受机械通气的 3551 名婴儿中有 203 名（5.7%）婴儿出现表面活性剂治疗遗漏，这与生存率较低（aOR，0.49；95%CI，0.30-0.82）相关。在足月出生的婴儿中，336 名（53.4%）接受表面活性剂治疗的婴儿患有胎粪吸入综合征。胎粪吸入时使用表面活性剂并没有改善新生儿结局。
在这项研究中，新生儿表面活性剂使用的最佳实践和标签的遵循情况各不相同，这对新生儿结局有重要的临床意义。
