Juber Brian A, Boly Timothy J, Pitcher Graeme J, McElroy Steven J
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, United States.
Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, United States.
Front Pediatr. 2021 Oct 28;9:757299. doi: 10.3389/fped.2021.757299. eCollection 2021.
Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity in preterm infants, and prevention and treatment strategies have remained largely unchanged over the past several decades. As understanding of the microbiome has increased, probiotics have been hypothesized as a possible strategy for decreasing rates of NEC, and several studies have noted significant decreases in rates of NEC after initiation of probiotics in preterm infants. However, a recent AAP report cited caution on the use of probiotic use in part because studies of probiotic use in ELBW infants are lacking. As our unit began routine use of probiotics for all infants <33 weeks in 2015 and we are a leading institution for intact survival of ELBW infants, we attempted to answer if probiotic use can impact the rate of NEC in VLBW and ELBW infants. We conducted a single-center retrospective chart review of infants with modified Bell's stage ≥2a NEC for the 4 years prior to and 5 years after initiation of a protocol involving routine supplementation of a multispecies probiotic to premature infants at the University of Iowa, Stead Family Children's Hospital. The primary outcome measures were rates of modified Bell's stage ≥2a NEC and all-cause pre-discharge mortality at our institution before and after initiation of routine probiotic supplementation in 2015. In our institution, neither the rates of modified Bell's stage ≥2a NEC, nor the rates of all-cause mortality were significantly altered in very low birth weight (VLBW) infants by the initiation of routine probiotic use (NEC rates pre-probiotic 2.1% vs. post-probiotic 1.5%; all-cause mortality rates pre-probiotic 8.4% vs. post-probiotic 7.4%). Characteristics of our two cohorts were overall similar except for a significantly lower 5-minute APGAR score in infants in the post-probiotic epoch (pre-probiotic 8 vs. post-probiotic 6 = 0.0316), and significantly more infants in the post-probiotic epoch received probiotics (pre-probiotics 0% vs. post-probiotics 65%; < 0.0001). Similarly, probiotic use had no impact on the incidence of NEC when we restricted our data to only extremely low birth weight (ELBW) infants (pre-probiotics 1.6% vs post-probiotics 4.1%). When we restricted our analysis to only inborn infants, probiotics still had no impact on NEC rates in VLBW infants (1.5% pre- and 1.1% post-probiotic, = 0.61) or ELBW infants (2% pre- and 2.1% post-probiotic, = 0.99) Contrary to other studies, we found no significant difference in rates of modified Bell's stage ≥2a NEC or all-cause pre-discharge mortality in VLBW infants following routine administration of a multispecies probiotic supplement.
坏死性小肠结肠炎（NEC）是早产儿胃肠道发病的主要原因，在过去几十年里，其预防和治疗策略基本没有变化。随着对微生物群的认识不断增加，益生菌被认为是降低NEC发病率的一种可能策略，多项研究指出，早产儿开始使用益生菌后，NEC发病率显著下降。然而，美国儿科学会（AAP）最近的一份报告对益生菌的使用提出了谨慎态度，部分原因是缺乏对超低出生体重（ELBW）婴儿使用益生菌的研究。由于我们的科室于2015年开始对所有孕周小于33周的婴儿常规使用益生菌，且我们是一家在ELBW婴儿完整存活方面处于领先地位的机构，我们试图回答使用益生菌是否会影响极低出生体重（VLBW）和ELBW婴儿的NEC发病率。我们对爱荷华大学斯特德家庭儿童医院实施一项涉及对早产儿常规补充多种益生菌方案之前4年和之后5年中，修正贝尔分期≥2a期NEC婴儿进行了单中心回顾性病历审查。主要结局指标是2015年开始常规补充益生菌前后，我们机构中修正贝尔分期≥2a期NEC的发病率以及全因出院前死亡率。在我们机构，常规使用益生菌后，极低出生体重（VLBW）婴儿的修正贝尔分期≥2a期NEC发病率和全因死亡率均未显著改变（使用益生菌前NEC发病率为2.1%，使用益生菌后为1.5%；使用益生菌前全因死亡率为8.4%，使用益生菌后为7.4%）。除了使用益生菌时期的婴儿5分钟阿氏评分显著更低（使用益生菌前为8分，使用益生菌后为6分，P = 0.0316），以及使用益生菌时期接受益生菌的婴儿显著更多（使用益生菌前为0%，使用益生菌后为65%，P < 0.0001）外，我们这两个队列的特征总体相似。同样，当我们将数据仅限制在超低出生体重（ELBW）婴儿时，使用益生菌对NEC发病率也没有影响（使用益生菌前为1.6%，使用益生菌后为4.1%）。当我们将分析仅限制在足月儿时，益生菌对VLBW婴儿（使用益生菌前为1.5%，使用益生菌后为1.1%，P = 0.61）或ELBW婴儿（使用益生菌前为2%，使用益生菌后为2.1%，P = 0.99）的NEC发病率仍没有影响。与其他研究相反，我们发现常规给予多种益生菌补充剂后，VLBW婴儿的修正贝尔分期≥2a期NEC发病率或全因出院前死亡率没有显著差异。
