Newcastle Hospitals NHS Trust, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
JAMA Netw Open. 2023 Mar 1;6(3):e231165. doi: 10.1001/jamanetworkopen.2023.1165.
The effect of using an exclusive human milk diet compared with one that uses bovine products in preterm infants is uncertain, but some studies demonstrate lower rates of key neonatal morbidities. A potential mediating pathway is the gut microbiome.
To determine the effect of an exclusive human milk diet on gut bacterial richness, diversity, and proportions of specific taxa in preterm infants from enrollment to 34 weeks' postmenstrual age.
DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial conducted at 4 neonatal intensive care units in the United Kingdom from 2017 to 2020, microbiome analyses were blind to group. Infants less than 30 weeks' gestation who had only received own mother's milk were recruited before 72 hours of age. Statistical analysis was performed from July 2019 to September 2021.
Exclusive human milk diet using pasteurized human milk for any shortfall in mother's own milk supply and human milk-derived fortifiers (intervention) compared with bovine formula and bovine-derived fortifier (control) until 34 weeks' postmenstrual age. Fortifier commenced less than 48 hours of tolerating 150 mL/kg per day.
Gut microbiome profile including alpha and beta diversity, and presence of specific bacterial taxa.
Of 126 preterm infants enrolled in the study, 63 were randomized to control (median [IQR] gestation: 27.0 weeks [26.0-28.1 weeks]; median [IQR] birthweight: 910 g [704-1054 g]; 32 [51%] male) and 63 were randomized to intervention (median [IQR] gestation: 27.1 weeks [25.7-28.1 weeks]; median [IQR] birthweight: 930 g [733-1095 g]; 38 [60%] male); 472 stool samples from 116 infants were analyzed. There were no differences in bacterial richness or Shannon diversity over time, or at 34 weeks between trial groups. The exclusive human milk diet group had reduced relative abundance of Lactobacillus after adjustment for confounders (coefficient estimate, 0.056; P = .03), but not after false discovery rate adjustment. There were no differences in time to full feeds, necrotizing enterocolitis, or other key neonatal morbidities.
In this randomized clinical trial in preterm infants using human milk-derived formula and/or fortifier to enable an exclusive human milk diet, there were no effects on overall measures of gut bacterial diversity but there were effects on specific bacterial taxa previously associated with human milk receipt. These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms.
ISRCTN trial registry identifier: ISRCTN16799022.
与使用牛产品的配方奶相比，早产儿使用纯人乳喂养的效果尚不确定，但一些研究表明其能降低主要新生儿发病率。潜在的中介途径是肠道微生物组。
确定纯人乳喂养对早产儿肠道细菌丰富度、多样性和特定分类群比例的影响，研究对象从入组到校正胎龄 34 周。
设计、地点和参与者：本随机临床试验于 2017 年至 2020 年在英国的 4 家新生儿重症监护病房进行，微生物组分析对组间情况设盲。招募胎龄小于 30 周且仅接受母亲人乳的婴儿，入组时间在生后 72 小时内。统计分析于 2019 年 7 月至 2021 年 9 月进行。
人乳不足部分用巴氏消毒的人乳补充，且使用人乳来源的强化剂（干预组），而非牛配方和牛来源的强化剂（对照组），直到校正胎龄 34 周。强化剂起始时间在耐受 150 mL/kg/天的 48 小时内。
肠道微生物组谱，包括 alpha 和 beta 多样性，以及特定细菌分类群的存在。
在本研究中，共有 126 名早产儿入组，其中 63 名随机分为对照组（中位[IQR]胎龄：27.0 周[26.0-28.1 周]；中位[IQR]出生体重：910 g[704-1054 g]；32 名[51%]男性），63 名随机分为干预组（中位[IQR]胎龄：27.1 周[25.7-28.1 周]；中位[IQR]出生体重：930 g[733-1095 g]；38 名[60%]男性）；116 名婴儿中有 472 个粪便样本进行了分析。试验组间，无论时间还是校正胎龄 34 周时，细菌丰富度或 Shannon 多样性均无差异。经混杂因素校正后，干预组的乳酸杆菌相对丰度降低（系数估计值，0.056；P = .03），但经假发现率校正后则无差异。两组间全肠内营养时间、坏死性小肠结肠炎或其他主要新生儿发病率均无差异。
在本项针对使用人乳来源配方和/或强化剂以实现纯人乳喂养的早产儿的随机临床试验中，肠道细菌多样性的总体测量无影响，但与接受人乳相关的特定细菌分类群有影响。这些发现提示人乳来源产品的临床影响并非通过微生物组机制调节。
ISRCTN 临床试验注册平台，注册号：ISRCTN82631646。
