Beneficial Effects of Breast Milk in the Neonatal Intensive Care Unit on the Developmental Outcome of Extremely Low Birth Weight Infants at 18 Months of Age
OBJECTIVE. Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously.METHODS. Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months’ corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age were assessed.RESULTS. There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 ± 9 days. Infants in the breast milk group began to ingest non–breast milk formula later (22.8 vs 7.3 days) compared with the non–breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non–breast milk groups (29.0 ± 18 vs 27.4 ± 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non–breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (≤$20000), or had higher parity were less likely to provide breast milk feeds. The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age, maternal education, marital status, race/ethnicity, and the other standard covariates. Children in the breast milk group were more likely to have a Bayley Mental Development Index ≥85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization 1 year), only the values for the 80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyses, every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 × 0.53, or 5.3 points.CONCLUSIONS. An increase of 5 points potentially would
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机译：目的。先前已经在足月和极低出生体重的婴儿中证明了母乳对认知技能和行为评级的有益作用。众所周知，极低出生体重的婴儿发生发育和行为疾病的风险增加。先前尚未评估极低出生体重婴儿在重症监护病房（NICU）中摄取母乳对发育和行为的益处。前瞻性地收集了包括肠内和肠外喂养在内的营养数据，并在美国儿童健康与人类发展研究所新生儿研究网络的15个地点完成了对1035名18个月校正年龄的极低出生体重婴儿的随访评估。在1999年10月14日至2001年6月25日之间进行谷氨酰胺试验。计算了住院期间母乳喂养的总量（mL / kg /天）。评估了校正后18至22个月的新生儿的特征和发病率，中期病史以及神经发育和生长结果。无母乳组中有775名（74.9％）婴儿，无母乳组中有260名（25.1％）婴儿。在所有新生儿特征和发病率（包括住院天数）方面，母乳组的婴儿与无母乳组的婴儿相似。母乳喂养婴儿第一天的平均年龄为9.3±9天。与非母乳组相比，母乳组中的婴儿后来开始摄入非母乳配方食品（22.8 vs 7.3天）。母乳和非母乳组达到完全肠内喂养的年龄相似（29.0±18 vs 27.4±15）。母乳组和非母乳组的住院期间能量摄入分别为107.5 kg /天和105.9 kg /天没有差异。出院时，母乳组中30.6％的婴儿仍在接受母乳。母乳喂养组的母亲更有可能是白人（42％vs 27％），已婚（50％vs 30％），具有大学学历（22％vs 6％）和私人健康保险（34） ％和18％）相比，没有母乳组。黑人，家庭收入低（≤20000美元）或较高的母亲提供母乳喂养的可能性较小。根据母体年龄，母体受教育程度，婚姻状况，种族/民族和其他标准协变量，对任何母乳和无母乳组之间的结果分析进行了调整。母乳组中的儿童更有可能具有≥85的贝利心理发展指数，较高的贝利心理运动发展指数平均值和较高的贝利行为评估量表百分位分数，用于定向/参与，运动调节和总分。在两个研究组之间，中度至重度脑瘫或失明或听力障碍的发生率无差异。在18个月时，母乳组和没有母乳组的平均体重（10.4公斤对10.4公斤），长度（80.5厘米对80.5厘米）或头围（46.8厘米对46.6厘米）没有差异。 。校正混杂因素的多元分析证实，母乳在所有四个主要结局上均具有显着的独立关联：平均Bayley（心理发展指数，心理运动发展指数，行为评定量表和再次住院的发生率）。母乳摄入量每天每增加10 mL / kg，精神发育指数增加0.53点，精神运动发育指数增加0.63点，行为评级量表百分位数得分增加0.82点，而再次住院的可能性降低减少6％。为了确定母乳对贝利心理发育指数，精神运动发育指数和行为评定量表百分位数的阈值影响，计算了住院期间每公斤每天的母乳平均量，并对母乳中的婴儿进行了计算。分组将母乳摄入量的五分位数调整为混杂因素。总体而言，心理发育指数和精神运动发育指数的五分位数喂养差异很大。最低和最高五分位数之间的行为评级量表得分相差14.0％。对于结局（心理发展指数，心理运动发展指数，行为评级量表和重新住院<1年），仅母乳喂养的> 80％的五分位数的值与无母乳的值显着不同。在我们进行的回归分析中，每天每10 mL / kg母乳对Bayley心理发展指数的贡献为0.53点;因此，在最高五分位数（每天110 mL / kg的婴儿）住院期间，母乳摄入对贝利心理发展指数的影响为10×0.53，即5.3点。结论。增加5分可能
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