乳糖酶添加剂对早产儿乳糖不耐受有效性及安全性：一项前瞻性、多中心、随机对照研究

doi:10.12372/jcp.2023.22e1095

临床儿科杂志 ›› 2023, Vol. 41 ›› Issue (1): 34-41.doi: 10.12372/jcp.2023.22e1095

乳糖酶添加剂对早产儿乳糖不耐受有效性及安全性：一项前瞻性、多中心、随机对照研究

查新祎¹, 王依闻¹, 毛朋亮², 陈鸣艳³, 蒋玮⁴, 王华伟⁴, 胡雪峰²(), 施丽萍³(), 朱雪萍⁴(), 钱继红¹()

1.上海交通大学医学院附属新华医院新生儿科（上海 200092）
2.上海市第一妇婴保健院新生儿科（上海 201204）
3.浙江大学医学院附属儿童医院新生儿重症监护室（浙江杭州 310003）
4.苏州大学附属儿童医院新生儿科（江苏苏州 215025）

收稿日期:2022-08-15 出版日期:2023-01-15 发布日期:2023-02-16
通讯作者: 胡雪峰,施丽萍,朱雪萍,钱继红 E-mail:1021501215@qq.com;slping2008@163.com;zhuxueping4637@hotmail.com;qianjihong@xinhuamed.com.cn

Efficacy and safety of lactase additive in preterm infants with lactose intolerance: a prospective, multi-center, randomized controlled trial

ZHA Xinyi¹, WANG Yiwen¹, MAO Pengliang², CHEN Mingyan³, JIANG Wei⁴, WANG Huawei⁴, HU Xuefeng²(), SHI Liping³(), ZHU Xueping⁴(), QIAN Jihong¹()

1. Department of Neonatology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
2. Department of Neonatology, Shanghai First Maternity and Infant Hospital, Shanghai 201204, China
3. Neonatal Intensive Care Unit, The Children’s Hospital, Zhejiang University of Medicine, Hangzhou 310003, Zhejiang, China
4. Department of Neonatology, Children’s Hospital of Soochow University, Suzhou 215025, Jiangsu, China

Received:2022-08-15 Online:2023-01-15 Published:2023-02-16
Contact: HU Xuefeng,SHI Liping,ZHU Xueping,QIAN Jihong E-mail:1021501215@qq.com;slping2008@163.com;zhuxueping4637@hotmail.com;qianjihong@xinhuamed.com.cn

摘要/Abstract

摘要： 目的探讨乳糖酶添加剂对早产儿乳糖不耐受改善的有效性以及安全性。方法 2018年1月至2019年12月对上海交通大学医学院附属新华医院、上海市第一妇婴保健院、浙江大学医学院附属儿童医院和苏州大学附属儿童医院收治的有乳糖不耐受症状并符合入组标准的早产儿进行研究，将研究对象随机分为乳糖酶治疗组及对照组，各80例。乳糖酶治疗组患儿每顿母乳或早产儿配方奶中加入4滴（180 mg）乳糖酶，同时予双歧杆菌三联活菌散口服及腹部按摩作为辅助治疗。对照组患儿则在每顿奶中加入同等剂量的安慰剂，并予与治疗组相同的益生菌和腹部按摩进行辅助治疗。在干预后第1周末和第2周末比较两组患儿临床症状、体重、粪便pH值、粪便还原糖等指标。结果乳糖酶治疗组和对照组分别有78例、77例完成研究。干预后第1周末，乳糖酶治疗组还原糖阳性率较对照组低（P<0.05）；干预后第2周末，乳糖酶治疗组患儿腹胀发生率较对照组低（P<0.05），还原糖阳性率低于对照组（P<0.05），同时乳糖酶治疗组患儿喂养增加量高于对照组（P<0.05）。研究过程中两组均未发现患儿对乳糖酶添加剂或益生菌产生不良反应。结论外源性乳糖酶添加剂可有效并且安全地缓解早产儿乳糖不耐受相关的临床症状。

关键词: 乳糖不耐受, 乳糖酶添加剂, 安全性, 有效性, 早产儿

Abstract: Objective To explore the efficacy and safety of lactase additive in improving lactose intolerance in premature infants. Methods Preterm infants with lactose intolerance admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai First Maternal and Infant Health Hospital, Children's Hospital Affiliated to Zhejiang University School of Medicine and Children's Hospital Affiliated to Soochow University from January 2018 to December 2019, who met the inclusion criteria were included in the study. They were divided into lactase treatment group and control group randomly, with 80 cases in each group. For the patients in the lactase treatment group, 4 drops (180 mg) of lactase were added to each feeding of breast milk or formula milk for premature infants, and Bifidobacterium triple viable powder was orally administered and abdominal massage was used as adjuvant therapy. For patients in the control group, 4 drops (180 mg) of placebo were added to each feeding, and the same probiotics and abdominal massage as the treatment group were given, After 1 and 2 weeks treatment, symptoms of lactose intolerance, weight, fecal pH, fecal reducing sugar and other indicators were compared between the two groups. Results seventy-eight patients in the lactase treatment group and 77 patients in the control group, respectively, completed the whole study. After the first week intervention, the positive rate of reducing sugar in the lactase treatment group was lower than that in the control group (P<0.05). At the end of the second week treatment, the proportion of abdominal distension in the lactase treatment group were lower than those in the control group (P<0.05), and the positive rate of reducing sugar was lower than that in the control group (P<0.05). The increase of feeding amount was also higher than that of the control group (P<0.05). During the course of the study, no adverse reactions to lactase additives or probiotics were found in both groups. Conclusions Lactase supplementation can effectively and safely improve the clinical symptoms caused by lactose intolerance in premature infants.

Key words: lactose intolerance, lactase supplement, safety, efficacy, premature infant

查新祎, 王依闻, 毛朋亮, 陈鸣艳, 蒋玮, 王华伟, 胡雪峰, 施丽萍, 朱雪萍, 钱继红. 乳糖酶添加剂对早产儿乳糖不耐受有效性及安全性：一项前瞻性、多中心、随机对照研究[J]. 临床儿科杂志, 2023, 41(1): 34-41.

ZHA Xinyi, WANG Yiwen, MAO Pengliang, CHEN Mingyan, JIANG Wei, WANG Huawei, HU Xuefeng, SHI Liping, ZHU Xueping, QIAN Jihong. Efficacy and safety of lactase additive in preterm infants with lactose intolerance: a prospective, multi-center, randomized controlled trial[J]. Journal of Clinical Pediatrics, 2023, 41(1): 34-41.

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医院	组别	例数	胎龄 [x±s/M(P₂₅~P₇₅)]/周	性别（男） [n(%)]	入组日龄 [M(P₂₅~P₇₅)]/d	入组体重 [x±s/M(P₂₅~P₇₅)]/g
上海新华医院	对照组	20	31.42±2.15	10(50.0)	9.00(2.25~16.00)	1641.80±389.22
	乳糖酶治疗组	29	30.78±2.30	13(44.8)	8.00（3.00~15.50）	1536.66±407.88
	统计量		t=0.98	χ²=0.13	Z=0.05	t=0.903
	P		0.33	0.72	0.96	0.37
上海市第一妇婴保健院	对照组	26	29.71(28.40~31.54)	13(50.0)	17.00(12.50~22.25)	1521.54±393.28
	乳糖酶治疗组	14	30.86(29.25~34.14)	10(71.40)	21.00(11.25~24.00)	1498.93±346.97
	统计量		Z=1.32	χ²=1.71	Z=0.55	t=0.18
	P		0.19	0.19	0.58	0.86
浙江大学医学院附属儿童医院	对照组	11	29.21±1.11	6(54.5)	34.00(23.00~43.00)	1 822.73±354.04
	乳糖酶治疗组	14	29.47±1.49	9(64.3)	32.00(21.75~39.00)	1 939.29±346.71
	统计量		t=0.49	?-	Z=0.44	t=0.83
	P		0.63	0.70¹⁾	0.66	0.42
苏州大学附属儿童医院	对照组	20	32.43(31.25~33.86)	11(55.00)	12.00(5.75~17.75)	1 755.00 (1 645.00~2 392.50)
	乳糖酶治疗组	21	33.57（31.79~35.43）	10(47.60)	10.00(5.00~18.00)	2 020.00 (1 560.00~2 400.00)
	统计量		Z=1.31	χ²=0.22	Z=0.34	Z=0.55
	P		0.19	0.64	0.73	0.58

项目	对照组(n=77)	乳糖酶治疗组(n=78)	统计量	P
母乳喂养[n(%)]	46(59.74)	41(52.56)	χ²=0.81	0.37
入组时喂养量[M(P₂₅~P₇₅)]/mL·kg^-1·d^-1	88.00（46.75~131.05）	75.10（38.78~102.55）	Z=1.46	0.14
第1周末
喂养量（x±s）/mL·kg^-1·d^-1	128.12±36.51	123.56±34.26	t=0.80	0.42
喂养量增加[M(P₂₅~P₇₅)]/mL·kg^-1·d^-1	38.54（3.00~69.14）	46.85（19.00~76.83）	Z=1.26	0.21
第2周末
喂养量（x±s）/mL·kg^-1·d^-1	145.83±29.23	154.70±29.90	t=1.85	0.06
喂养量增加[M(P₂₅~P₇₅)]/mL·kg^-1·d^-1	62.00（16.13~94.70）	74.50（41.75~126.35）	Z=2.25	0.02

项目	对照组(n=77)	乳糖酶治疗组(n=78)	统计量	P
入组时
吐奶[n(%)]	12(15.58)	22(28.21)	χ²=3.60	0.06
腹胀[n(%)]	48(62.34)	39(50.00)	χ²=3.43	0.06
每日排便次数[M(P₂₅~P₇₅)]/次	2.00（1.00~4.00）	2.50（1.00~4.00）	Z=0.72	0.47
第1周末
吐奶[n(%)]	2(2.60)^1）	2(2.56)^1）	-	1.00³⁾
腹胀[n(%)]	24(31.17)^2）	15(19.23)^2）	χ²=2.96	0.09
每日排便次数[M(P₂₅~P₇₅)]/次	2.00(1.00~3.00)	2.00(1.00~3.00)	Z=0.04	0.96
第2周末
吐奶[n(%)]	0(0.00)¹⁾	1(1.28)¹⁾	-	1.00³⁾
腹胀[n(%)]	18(23.38)²⁾	2(2.56)²⁾	χ²=15.74	<0.01
每日排便次数[M(P₂₅~P₇₅)]/次	2.00(1.00~3.00)	2.00(1.00~3.00)	Z=0.04	0.96

项目	对照组(n=77)	乳糖酶治疗组(n=78)	统计量	P
入组时
粪便pH值阳性[n(%)]	36（46.75）	42（53.84）	χ²=0.78	0.38
还原糖[M(P₂₅~P₇₅)]/%	0.50（0.50~1.00）	0.50（0.50~1.00）	Z=0.30	0.77
还原糖阳性[n(%)]	77（100）	78（100）	-	-
第1周末
粪便pH值阳性[n(%)]	31（40.26）	35（44.87）	χ²=0.34	0.56
还原糖[M(P₂₅~P₇₅)]/%	0.50（0.25~1.00）	0.25（0.00~0.50）	Z=4.09	<0.01
还原糖阳性[n(%)]	65(84.42)	49(62.82)	χ²=9.29	<0.01
第2周末
粪便pH值阳性[n(%)]	28(36.36)	34(43.59)	χ²=0.84	0.36
还原糖[M(P₂₅~P₇₅)]/%	0.25（0.00~0.50）	0.00（0.00~0.25）	Z=3.22	<0.01
还原糖阳性[n(%)]	45(58.44)	24(30.77)	χ²=12.15	<0.01

项目	对照组(n=77)	乳糖酶治疗组(n=78)	t值	P
入组时
体重(x±s)/g	1 699.69±414.21	1 778.69±494.76	1.08	0.28
第1周末
体重(x±s)/g	1 860.13±422.73	1 962.41±540.79	1.31	0.19
t值	12.14	10.73
P	<0.01	<0.01
第2周末
体重(x±s)/g	2 058.83±463.33	2 157.65±585.01	1.17	0.25
t值	17.87	17.08
P	<0.01	<0.01

乳糖酶添加剂对早产儿乳糖不耐受有效性及安全性：一项前瞻性、多中心、随机对照研究

Efficacy and safety of lactase additive in preterm infants with lactose intolerance: a prospective, multi-center, randomized controlled trial

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