Disposable low-cost cardboard incubator for thermoregulation of stable preterm infant – a randomized controlled non-inferiority trial

Study objective: We determined whether thermoregulation of stable preterm infants at post-menstrual age 32 to 36 weeks and weight 1250 to 2250 grams in the low-cost incubator and thermoregulation of infants in standard single-wall incubator for 48 hours are comparable.

Study end points: Maintaining axillary and skin temperature of infant in normal range from 36.5°C to 37.5°C for a period of 48 hours. If abnormal temperature i.e., axillary temperature < 36.5°C / > 37.5°C or apnea requiring bag and mask ventilation or any abnormal vital signs persisting for a duration exceeding 30 minutes infants would be taken out of study, and managed as per standard guidelines. We checked if the infants in low-cost incubator were maintaining hourly skin temperature, and axillary temperature measured 4th hourly were within non-inferiority limit of 0.2C.

Place of study: Single centre study, in step-down neonatal intensive care unit and ‘KMC ward’ of Sri Ramachandra Medical College and Research Centre.

Study intervention: Study incubators were assembled after hospital disinfection policy. After negative surface culture of incubators, infants were randomly nursed in either low-cost incubator or standard single-wall incubator in air-control mode and set-incubator temperature as per standard guidelines for 48 hours. Infant’s skin temperature measured by thermistor skin probe, axillary temperature measured by digital thermometer and vital signs were monitored. Incubator and ambient room temperature, humidity details measured by digital thermohygrometer were recorded. If infant develops any adverse events infant were taken out of study incubator and managed as per attending clinician decisions. Infants were observed till discharge for any untoward adverse events. Surface culture were taken from study incubators on day 3, day 5 and day 7 and incubators worked for 5 days in last set-air temperature. In post-infant period incubators are monitored by microbiology, temperature and humidity monitoring from day 3 to day 7.

Findings: Median weight at enrollment for infants < 33 weeks and >= 33 weeks were similar in both groups. Mean skin and axillary temperature were lower in low-cost incubator group, but within the non-inferiority limit 0.2 C. In view of repeated measures, mixed model estimate for skin and axillary temperature were also within non-inferiority limit. ‘Failed thermoregulation’ occurred in none. Mild hypothermia occurred in 23% of standard incubator group and 33% low-cost incubator group. Incubator temperature in low-cost incubator was slightly higher. In post-infant period standard incubator and low cost incubator had excellent agreement to maintain set-temperature.

Baseline characteristics, skin temperature, axillary temperature, incubator temperature, incubator humidity, room temperature, room humidity during 48 hour infant period and post-infant monitoring period are provided. Incubator surface culture details, nurses feedback of incubator are provided.

研究目的：本研究旨在验证，校正胎龄（post-menstrual age）32~36周、体重1250~2250g的病情稳定早产儿，在低成本暖箱（low-cost incubator）中的体温调节（thermoregulation）效果，与标准单层壁暖箱（standard single-wall incubator）中持续48小时的体温调节效果是否具有可比性。

研究终点：需维持患儿腋温（axillary temperature）及皮温（skin temperature）处于36.5℃~37.5℃的正常范围，时长共计48小时。若出现异常体温（即腋温<36.5℃或>37.5℃）、需行球囊面罩通气（bag and mask ventilation）的呼吸暂停（apnea），或任何持续时长超过30分钟的异常生命体征（vital signs），则将该患儿退出研究，并按照标准临床指南进行处理。本研究将评估低成本暖箱组患儿的皮温是否每小时维持稳定，且每4小时测量的腋温是否处于0.2℃的非劣效界值（non-inferiority limit）范围内。

研究地点：本研究为单中心研究，开展于斯里拉玛昌德拉医学院及研究中心的过渡新生儿重症监护病房（step-down neonatal intensive care unit）与KMC病房（Kangaroo Mother Care Ward，即袋鼠护理病房）。

研究干预：研究用暖箱按照医院消毒政策完成组装，经表面培养结果为阴性后，将患儿随机分配至低成本暖箱组或标准单层壁暖箱组，采用空气控制模式，并按照标准指南设置暖箱温度，持续干预48小时。采用热敏电阻皮温探头测量患儿皮温，电子体温计测量腋温，并持续监测生命体征。记录由电子温湿度计测得的暖箱及病房环境温度、湿度数据。若患儿出现任何不良事件，则将其移出研究用暖箱，并按照主管医师的决策进行临床处置。对患儿直至出院期间的所有不良事件进行追踪观察。分别于研究第3、5、7天采集研究用暖箱的表面培养样本，且暖箱在最后一次设置空气温度后需持续运行5天。在患儿出组后的监测阶段，于第3至7天对暖箱开展微生物学监测、温度及湿度监测。

研究结果：入组时胎龄<33周与≥33周的患儿的中位体重在两组间无显著差异。低成本暖箱组的平均皮温及腋温略低于标准单层壁暖箱组，但仍处于0.2℃的非劣效界值范围内。考虑到重复测量的研究设计，皮温及腋温的混合效应模型（mixed model）估计值同样处于非劣效界值范围内。无患儿出现体温调节失败情况。标准单层壁暖箱组有23%的患儿出现轻度低体温（mild hypothermia），低成本暖箱组则为33%。低成本暖箱的暖箱温度略高于标准组。患儿出组后，两类暖箱在维持设定温度方面表现出极佳的一致性。

数据集内容说明：本研究提供以下数据：患儿基线特征、48小时研究期间及患儿出组后监测期内的皮温、腋温、暖箱温度、暖箱湿度、病房温度、病房湿度数据；暖箱表面培养详情及护理人员对暖箱的反馈意见。