Casper Charlotte, Carnielli Virgilio P, Hascoet Jean-Michel, Lapillonne Alexandre, Maggio Luca, Timdahl Kristina, Olsson Birgitta, Vågerö Mårten, Hernell Olle
*Unit of Neonatology, Children's Hospital, Paul Sabatier University Toulouse, Toulouse, France †Division of Neonatology, Polytechnic University of Marche and Salesi's Children Hospital, Ancona, Italy ‡Department of Neonatology, Maternite Regionale, Université de Lorraine, Nancy §Department of Neonatology, Assistance Publique Hôpitaux de Paris Necker Hospital, Paris Descartes University, Paris, France ||Division of Neonatology, Department of Pediatrics, Catholic University Sacred Heart, Rome, Italy ¶Swedish Orphan Biovitrum (Sobi), Stockholm #Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
J Pediatr Gastroenterol Nutr. 2014 Jul;59(1):61-9. doi: 10.1097/MPG.0000000000000365.
Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt-stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula.
Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design.
Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g · kg · day (P<0.001) compared with placebo (mean 16.86 vs 13.93 g · kg · day) and significantly decreased the risk of suboptimal growth (<15 g · kg · day) (30% vs 52%, P=0.004). rhBSSL significantly increased absorption of the long-chain polyunsaturated fatty acids, docosahexaenoic acid, and arachidonic acid by 5.76% (P=0.013) and 8.55% (P=0.001), respectively, but had no significant effect on total fat absorption. The adverse-event profile was similar to placebo.
In preterm infants fed pasteurized breast milk or formula, 1 week of treatment with rhBSSL was well tolerated and significantly improved growth and long-chain polyunsaturated fatty acid absorption compared to placebo. This publication presents the first data regarding the use of rhBSSL in preterms and the results have led to further clinical studies.
早产儿常出现生长欠佳，这会影响器官发育。本研究的目的是通过使用胆汁盐刺激脂肪酶（BSSL）进行治疗来改善生长情况，BSSL天然存在于母乳中，但在巴氏杀菌后会丧失，且配方奶中不存在。
进行了两项临床试验，并对合并数据进行预定义分析，以研究重组人BSSL（rhBSSL）治疗对早产儿生长速度和脂肪吸收的影响。研究采用交叉设计，随机、双盲比较在巴氏杀菌母乳或配方奶中给予rhBSSL和安慰剂7天治疗的效果。
对63名婴儿进行了安全性评估。随机分组时，平均（标准差）体重为1467（193）g，平均月经后年龄为32.6（0.5）周。分别对60名和46名婴儿进行了生长速度和脂肪吸收评估。与安慰剂相比，rhBSSL治疗显著提高了平均生长速度2.93 g·kg·天（P<0.001）（平均分别为16.86和13.93 g·kg·天），并显著降低了生长欠佳（<15 g·kg·天）的风险（30%对52%，P=0.004）。rhBSSL分别使长链多不饱和脂肪酸二十二碳六烯酸和花生四烯酸的吸收显著增加5.76%（P=0.013）和8.55%（P=0.001），但对总脂肪吸收无显著影响。不良事件情况与安慰剂相似。
在喂食巴氏杀菌母乳或配方奶的早产儿中，与安慰剂相比，rhBSSL治疗1周耐受性良好，显著改善了生长情况和长链多不饱和脂肪酸吸收。本出版物展示了关于rhBSSL在早产儿中使用的首批数据，其结果已促使开展进一步的临床研究。
