乳糖酶滴剂对早产儿乳糖不耐受有效性和安全性的多中心研究

Multi-Center Study on Efficacy and Safety of Lactase Drops in the Treatment of Lactose Intolerance in Premature Infants

目的:评估乳糖酶滴剂对早产儿乳糖不耐受的有效性、安全性,提高早产儿的母乳喂养率。方法:采用多中心非随机对照临床研究,以复旦大学附属儿科医院、上海交通大学附属上海儿童医学中心和上海市儿童医院新生儿科收治的胎龄≤34周、有喂养不耐受症状的早产儿作为研究对象,非随机分为研究组和对照组。研究组患儿给予母乳+乳糖酶或早产儿液奶+乳糖酶进行喂养,对照组患儿使用深度水解无乳糖配方或氨基酸配方进行喂养。主要观察指标为乳糖不耐受症状、大便pH和粪便还原糖;次要观察指标为生长发育指标。结果:2017年7月至2020年7月共117例早产儿入组,研究组56例和对照组18例患儿完成研究。与对照组相比,研究组患儿入组2周体重增长速度大于对照组,差异有统计学意义(P<0.05)。两组患儿入组2周后大便次数减少情况、大便pH检测结果和粪便还原糖转阴患儿占比比较,差异均无统计学意义(P>0.05)。结论:乳糖酶和无乳糖配方奶均可有效治疗乳糖酶缺乏症。虽然乳糖酶起效较无乳糖配方奶缓慢,但母乳加乳糖酶喂养可以显著帮助患儿体重增长,且无需放弃母乳喂养。

OBJECTIVE: To evaluate the efficacy and safety of lactase drops in the treatment of lactose intolerance in premature infants, so as to promote the breastfeeding rate of premature infants. METHODS: A multi-center and non-randomized controlled clinical study was conduct, preterm infants with gestational age ≤34 weeks and symptoms of feeding intolerance admitted to neonatology departments of the Children’s Hospital of Fudan University, the Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University and the Children’s Hospital of Shanghai were selected as research objects, which were divided into research group and control group via non-randomized method. The research group was given breast milk + lactase or liquid milk for preterm infants + lactase, while the control group was fed with deeply hydrolyzed lactose-free formula or amino acid formula. The primary observation indicators were lactose intolerance symptoms, stool pH and fecal reducing sugar;the secondary observation indicators were growth and development indicators. RESULTS: A total of 117 premature infants were enrolled from Jul. 2017 to Jul. 2020, finally 56 children in the research group and 18 children in the control group had completed the study. Compared with the control group, the research group had a greater rate of weight gain at 2 weeks of enrollment, with statistically significant difference(P<0.05). There was no statistical significance in differences in the reduction of stool frequency, results of stool pH test and percentage of negative conversion of fecal reducing sugar between two groups after 2 weeks of enrollment(P>0.05). CONCLUSIONS: Both lactase and lactose-free formula can effectively treat lactase deficiency. Although the onset of action of lactase is slower than that of lactose-free formula, breast milk combined with lactase feeding can significantly help children’s weight gain without giving up breastfeeding.