Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Department of Pediatrics, Hennepin County Medical Center, Minneapolis, MN, USA; Bowen University Teaching Hospital, Ogbomosho, Oyo, Nigeria.
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Lancet Glob Health. 2018 Oct;6(10):e1122-e1131. doi: 10.1016/S2214-109X(18)30373-5. Epub 2018 Aug 28.
Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia.
We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 μmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%.
Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 μW/cm/nm (IQR 21·4-56·4) in the FSPT group and 50·4 μW/cm/nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates.
FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants.
Thrasher Research Fund and National Center for Advancing Translational Sciences.
由严重新生儿高胆红素血症引起的核黄疸是低收入和中等收入国家可预防死亡和残疾的主要原因，部分原因是缺乏高质量的强化光疗。此前，我们表明，过滤阳光光疗（FSPT）对治疗轻度至中度新生儿高胆红素血症是有效且安全的。我们旨在将这些研究扩展到中度至重度高胆红素血症的婴儿。
我们在尼日利亚奥戈博索进行了一项前瞻性、随机对照非劣效性试验，模拟农村环境。胎龄 35 周或以上且总血清胆红素浓度达到高危新生儿推荐的年龄相关治疗水平或以上的 14 天或更年轻的近足月或足月婴儿被随机分配（1:1）至 FSPT 或强化电光照治疗（IEPT）。随机分配由计算机生成，临床医生以及参与者的父母或监护人都不知道分组分配。FSPT 在一个透明的聚碳酸酯房间内进行，房间内铺有商业遮光膜，可传输有效的光疗光线，阻挡紫外线，并减少红外线辐射。主要结局是疗效，仅基于可评估的治疗天数（即至少接受 4 小时光疗的天数），定义为 72 小时或更年轻的婴儿总血清胆红素浓度增加率小于 3.4 μmol/L/h，或大于 72 小时的婴儿总血清胆红素浓度降低。安全性定义为无持续低体温、高热、脱水或晒伤，并且基于所有治疗天数。分析采用意向治疗，非劣效性边缘为 10%。
2015 年 7 月 31 日至 2017 年 4 月 30 日期间，共纳入 174 名新生儿并进行随机分组：87 名接受 FSPT，87 名接受 IEPT。FSPT 组接受了 215 天的光疗，其中 82 天（38%）不可评估。IEPT 组接受了 219 天的光疗治疗，其中 67 天（31%）不可评估。FSPT 组的中值辐照度为 37.3 μW/cm/nm（IQR 21.4-56.4），IEPT 组为 50.4 μW/cm/nm（44.5-66.2）。FSPT 在 133 天的治疗中有效 116 天（87.2%）；IEPT 在 152 天的治疗中有效 135 天（88.8%）（平均差异-1.6%，95%CI-9.9 至 6.7；p=0.8165）。由于 CI 没有延伸到-10%以下，我们得出结论，FSPT 与 IEPT 相比并不差。所有新生儿的治疗均安全。
FSPT 治疗近足月和足月新生儿中重度新生儿高胆红素血症是安全且不逊于 IEPT 的。
Thrasher 研究基金和国家转化医学中心。
