Department of Neonatology, University Children's Hospital, Eberhard-Karls University, Tuebingen, Germany.
Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, and Pathobiochemistry, Department of Internal Medicine IV, University of Tuebingen, Tuebingen, Germany3Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, University of Tuebingen, Tuebingen, Germany4German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany.
JAMA Pediatr. 2017 Jan 1;171(1):16-22. doi: 10.1001/jamapediatrics.2016.2681.
Protein, supplied in currently available commercial fortifiers, may be inadequate to meet the requirements of very preterm infants; in addition, intraindividual and interindividual variability of human milk protein and energy content potentially contribute to unsatisfactory early postnatal growth.
To determine effects on growth of different levels of enteral protein supplementation in predominantly human milk-fed preterm infants.
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical and partially blinded single-center trial was conducted in a neonatal tertiary referral center in Germany. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth) were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (interquartile range [IQR]) gestational age at birth was 29.9 (28.7-31.2) weeks. All analyses were conducted in an intention-to-treat population.
Infants were randomly assigned to either a lower-protein (adding 1 g of bovine protein/100 mL of breast milk through a commercial human milk fortifier; n = 30) or a higher-protein group at a median (IQR) postnatal age of 7 (6-8) days. The higher-protein group (n = 30) received either standardized higher-protein supplementation (study fortifier adding 1.8 g of bovine protein/100 mL of breast milk [n = 15]) or individualized high-protein supplementation based on protein and fat content of administered breast milk (n = 15). Study interventions were continued for a median (IQR) of 41 (30-57) days and until definite discharge planning.
Primary outcome was weight gain (g/kg/d) from birth to the end of intervention.
Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth), 33 girls, were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (IQR) gestational age at birth was 29.9 (28.7-31.2) weeks. Demographic characteristics and hospital courses were similar in both groups, and birth weights ranged from 580 to 1495 g in the lower-protein group and 490 to 1470 g in the higher-protein group. Weight gain was similar in the lower- and higher-protein groups: mean (95% CI), 16.3 g/kg/d (15.4-17.1 g/kg/d) in the lower-protein group vs 16.0 g/kg/d (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in actual protein intake by 0.6 g/kg/d (0.4-0.7 g/kg/d) (P < .001). Head circumference and lower leg longitudinal growth were also similar, as was the proportion of cumulative total enteral feeding volume provided as breast milk: median (IQR) proportion of breast milk, 92% (79%-98%) in the lower-protein group vs 94% (62%-99%) in the higher-protein group (P = .89).
An increase in protein intake by 0.6 g/kg/d to a mean intake of 4.3 g/kg/d did not further enhance growth of very preterm infants with a median birth weight of 1200 g, who achieved near-fetal growth rates. This might point to a ceiling effect for enteral protein intake with respect to its influence on growth.
clinicaltrials.gov Identifier: NCT01773902.
目前市售的商业强化剂中所含的蛋白质可能不足以满足极早产儿的需求；此外，人乳蛋白质和能量含量的个体内和个体间变异性可能导致早期生长不令人满意。
确定不同水平的肠内蛋白质补充对以人乳为主喂养的早产儿生长的影响。
设计、地点和参与者：这是一项在德国一家新生儿三级转诊中心进行的随机临床和部分盲法单中心试验。2012 年 10 月至 2014 年 10 月期间共招募了 60 名早产儿（胎龄 <32 周，出生体重 <1500 克），其中包括 173 名符合条件的婴儿中的 35%。中位（四分位间距 [IQR]）出生胎龄为 29.9（28.7-31.2）周。所有分析均在意向治疗人群中进行。
婴儿在出生后中位数（IQR）7（6-8）天时随机分为低蛋白组（通过商业人乳强化剂添加 1 克牛蛋白/100 毫升母乳；n = 30）或高蛋白组。高蛋白组（n = 30）接受标准化高蛋白补充（研究强化剂添加 1.8 克牛蛋白/100 毫升母乳[n = 15]）或基于给予的母乳的蛋白质和脂肪含量的个体化高蛋白补充（n = 15）。研究干预措施持续中位数（IQR）41（30-57）天，直至明确出院计划。
主要结局是从出生到干预结束时的体重增加（g/kg/d）。
2012 年 10 月至 2014 年 10 月共招募了 60 名早产儿（胎龄 <32 周，出生体重 <1500 克），其中 33 名女孩，占符合条件的 173 名婴儿的 35%。中位（IQR）出生胎龄为 29.9（28.7-31.2）周。两组的人口统计学特征和住院过程相似，出生体重范围为低蛋白组 580 至 1495 克，高蛋白组 490 至 1470 克。低蛋白组和高蛋白组的体重增加相似：低蛋白组的平均（95%CI）为 16.3 g/kg/d（15.4-17.1 g/kg/d），高蛋白组为 16.0 g/kg/d（15.1-16.9 g/kg/d）（P = .70），尽管实际蛋白质摄入量增加了 0.6 g/kg/d（0.4-0.7 g/kg/d）（P < .001）。头围和小腿纵向生长也相似，累积总肠内喂养量中母乳的比例也相似：低蛋白组中位数（IQR）为 92%（79%-98%），高蛋白组为 94%（62%-99%）（P = .89）。
将蛋白质摄入量增加 0.6 g/kg/d 至平均摄入量 4.3 g/kg/d 并没有进一步提高中位出生体重为 1200 克的极早产儿的生长速度，他们达到了接近胎儿的生长速度。这可能表明肠内蛋白质摄入对生长的影响存在上限。
clinicaltrials.gov 标识符：NCT01773902。
