Patel Ravi M, Knezevic Andrea, Shenvi Neeta, Hinkes Michael, Keene Sarah, Roback John D, Easley Kirk A, Josephson Cassandra D
Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia.
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia.
JAMA. 2016 Mar 1;315(9):889-97. doi: 10.1001/jama.2016.1204.
Data regarding the contribution of red blood cell (RBC) transfusion and anemia to necrotizing enterocolitis (NEC) are conflicting. These associations have not been prospectively evaluated, accounting for repeated, time-varying exposures.
To determine the relationship between RBC transfusion, severe anemia, and NEC.
DESIGN, SETTING, AND PARTICIPANTS: In a secondary, prospective, multicenter observational cohort study from January 2010 to February 2014, very low-birth-weight (VLBW, ≤1500 g) infants, within 5 days of birth, were enrolled at 3 level III neonatal intensive care units in Atlanta, Georgia. Two hospitals were academically affiliated and 1 was a community hospital. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first). Multivariable competing-risks Cox regression was used, including adjustment for birth weight, center, breastfeeding, illness severity, and duration of initial antibiotic treatment, to evaluate the association between RBC transfusion, severe anemia, and NEC.
The primary exposure was RBC transfusion. The secondary exposure was severe anemia, defined a priori as a hemoglobin level of 8 g/dL or less. Both exposures were evaluated as time-varying covariates at weekly intervals.
Necrotizing enterocolitis, defined as Bell stage 2 or greater by preplanned adjudication. Mortality was evaluated as a competing risk.
Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4%) infants developed NEC. Thirty-two (5.4%) infants died (all cause). Fifty-three percent of infants (319) received a total of 1430 RBC transfusion exposures. The unadjusted cumulative incidence of NEC at week 8 among RBC transfusion-exposed infants was 9.9% (95% CI, 6.9%-14.2%) vs 4.6% (95% CI, 2.6%-8.0%) among those who were unexposed. In multivariable analysis, RBC transfusion in a given week was not significantly related to the rate of NEC (adjusted cause-specific hazard ratio, 0.44 [95% CI, 0.17-1.12]; P = .09). Based on evaluation of 4565 longitudinal measurements of hemoglobin (median, 7 per infant), the rate of NEC was significantly increased among VLBW infants with severe anemia in a given week compared with those who did not have severe anemia (adjusted cause-specific hazard ratio, 5.99 [95% CI, 2.00-18.0]; P = .001).
Among VLBW infants, severe anemia, but not RBC transfusion, was associated with an increased risk of NEC. Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing RBC transfusion.
关于红细胞（RBC）输血和贫血对坏死性小肠结肠炎（NEC）的影响的数据存在冲突。这些关联尚未经过前瞻性评估，未考虑重复的、随时间变化的暴露情况。
确定RBC输血、严重贫血与NEC之间的关系。
设计、背景和参与者：在一项2010年1月至2014年2月的二级前瞻性多中心观察性队列研究中，出生体重极低（VLBW，≤1500g）且出生后5天内的婴儿在佐治亚州亚特兰大的3家三级新生儿重症监护病房入组。其中2家医院为学术附属医院，1家为社区医院。婴儿接受随访至90天、出院、转至非研究附属医院或死亡（以先发生者为准）。采用多变量竞争风险Cox回归，包括对出生体重、中心、母乳喂养、疾病严重程度和初始抗生素治疗持续时间进行调整，以评估RBC输血、严重贫血与NEC之间的关联。
主要暴露因素为RBC输血。次要暴露因素为严重贫血，预先定义为血红蛋白水平≤8g/dL。两种暴露因素均作为每周变化的协变量进行评估。
坏死性小肠结肠炎，通过预先计划的判定定义为Bell分期2期或更高。将死亡率作为竞争风险进行评估。
在600名入组的VLBW婴儿中，598名接受了评估。44名（7.4%）婴儿发生了NEC。32名（5.4%）婴儿死亡（各种原因）。53%的婴儿（319名）共接受了1430次RBC输血暴露。在接受RBC输血的婴儿中，第8周时NEC的未调整累积发病率为9.9%（95%CI，6.9%-14.2%），而未暴露婴儿为4.6%（95%CI，2.6%-8.0%）。在多变量分析中，某一周的RBC输血与NEC发生率无显著相关性（调整后的特定病因风险比，0.44[95%CI，0.17-1.12]；P = 0.09）。根据对4565次血红蛋白纵向测量（中位数为每名婴儿7次）的评估，与无严重贫血的VLBW婴儿相比，某一周患有严重贫血的VLBW婴儿中NEC发生率显著增加（调整后的特定病因风险比，5.99[95%CI，2.00-18.0]；P = 0.001）。
在VLBW婴儿中，严重贫血而非RBC输血与NEC风险增加相关。需要进一步研究以评估预防严重贫血是否比尽量减少RBC输血更重要。
