Background

Necrotizing enterocolitis (NEC) is a major challenge for premature infants in neonatal intensive care units and efforts toward the search for indicators that could be used to predict the development of the disease have given limited results until now.

Methods

In this study, stools from 132 very low birth weight infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction. Eight infants (~6%) received a stage 3 NEC diagnosis. Their stools collected up to 10 days before diagnosis were included and matched with 14 non-NEC controls and tested by ELISA for the quantitation of eight biomarkers.

Results

Biomarkers were evaluated in all available stool samples leading to the identification of lipocalin-2 and calprotectin as the two most reliable predicting markers over the 10-day period prior to NEC development. Pooling the data for each infant confirmed the significance of lipocalin-2 and calprotectin, individually and in combination 1 week in advance of the NEC clinical diagnosis.

Conclusions

The lipocalin-2 and calprotectin tandem represents a significant biomarker signature for predicting NEC development. Although not yet fulfilling the “perfect biomarker” criteria, it represents a first step toward it.

Impact

• Stool biomarkers can be used to predict NEC development in very low birth weight infants more than a week before the diagnosis.

• LCN2 was identified as a new robust biomarker for predicting NEC development, which used in conjunction with CALPRO, allows the identification of more than half of the cases that will develop NEC in very low birth weight infants.

• Combining more stool markers with the LCN2/CALPRO tandem such as PGE2 can further improve the algorithm for the prediction of NEC development.

中文翻译：

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Lipocalin-2 和钙卫蛋白作为预测早产儿坏死性小肠结肠炎的粪便生物标志物

背景

坏死性小肠结肠炎 (NEC) 是新生儿重症监护病房早产儿面临的主要挑战，迄今为止，寻找可用于预测疾病发展的指标的努力取得了有限的结果。

方法

在这项研究中，在一项旨在调查粪便生物标志物预测 NEC 的潜力的多中心前瞻性研究的背景下，每天收集 132 名极低出生体重婴儿的粪便。八名婴儿 (~6%) 接受了 3 期 NEC 诊断。他们在诊断前 10 天收集的粪便被包括在内，并与 14 名非 NEC 对照匹配，并通过 ELISA 测试了八种生物标志物的定量。

结果

在所有可用的粪便样本中评估生物标志物，从而确定 lipocalin-2 和钙卫蛋白是 NEC 发展前 10 天内最可靠的两个预测标志物。汇总每个婴儿的数据证实了 lipocalin-2 和钙卫蛋白在 NEC 临床诊断前 1 周单独和组合的重要性。

结论

lipocalin-2 和钙卫蛋白串联代表了预测 NEC 发展的重要生物标志物特征。尽管尚未达到“完美的生物标志物”标准，但它代表了朝着它迈出的第一步。

影响

• 粪便生物标志物可用于在诊断前一周以上预测极低出生体重婴儿的 NEC 发展。

• LCN2 被确定为预测 NEC 发展的一种新的稳健生物标志物，与 CALPRO 结合使用，可以识别出一半以上将在极低出生体重婴儿中发展为 NEC 的病例。

• 将更多的粪便标志物与 PGE2 等 LCN2/CALPRO 串联组合可以进一步改进预测 NEC 发展的算法。