肠道脂肪酸结合蛋白作为复杂性和非复杂性坏死性小肠结肠炎的诊断标志物：一项前瞻性队列研究
Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study.
作者信息
Schurink Maarten, Kooi Elisabeth M W, Hulzebos Christian V, Kox Rozemarijn G, Groen Henk, Heineman Erik, Bos Arend F, Hulscher Jan B F
机构信息
Department of Paediatric Surgery, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
Department of Neonatology, University of Groningen, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands.
出版信息
PLoS One. 2015 Mar 20;10(3):e0121336. doi: 10.1371/journal.pone.0121336. eCollection 2015.
BACKGROUND
Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial was to determine the diagnostic value of I-FABP measured in plasma (I-FABPp) and urine (I-FABPu) for the presence of NEC, to evaluate I-FABP levels during NEC development, and to assess its prognostic value for the progression from suspected to complicated disease.
METHODS
Between 2010 and 2012 we prospectively enrolled neonates with suspected NEC. We measured I-FABP levels eight-hourly from onset of suspected NEC for at least 48 hours, or until surgery. NEC diagnosis was confirmed radiologically or during operation. We defined NEC as complicated if it resulted in surgery and/or death. We determined disease course and diagnostic I-FABP cut-off points.
RESULTS
The study comprised 37 neonates (24M, 13F), gestational age 28 (24-36) weeks, birth weight 1190 (570-2,400) grams. We found significantly higher I-FABPp and I-FABPu levels in NEC patients (n = 22) than in patients with other diagnoses (n = 15). Cut-off values for diagnosing NEC were 9 ng/mL I-FABPp and 218 ng/mL I-FABPu, with corresponding likelihood ratios (LRs) of 5.6 (95% CI 0.89-35) and 5.1 (95% CI 0.73-36), respectively. I-FABP levels were highest in the first eight hours after symptom onset and gradually decreased over time. Cut-off values for complicated disease were 19 ng/mL I-FABPp and 232 ng/mL I-FABPu, with LRs of 10 (95% CI 1.6-70) and 11 (95% CI 1.6-81), respectively.
CONCLUSIONS
Both plasma and urinary I-FABP levels specifically identify NEC in preterm infants prior to appearance of diagnostic radiological signs suggestive for NEC. Moreover, serial I-FABP measurements accurately predict development of complicated disease.
背景
早期坏死性小肠结肠炎（NEC）症状不具特异性，诊断性检查缺乏鉴别能力。肠脂肪酸结合蛋白（I-FABP）主要位于小肠肠细胞中，在与NEC相关的肠细胞破坏后释放到血液中。这项前瞻性队列试验的目的是确定血浆（I-FABPp）和尿液（I-FABPu）中测量的I-FABP对NEC存在的诊断价值，评估NEC发展过程中的I-FABP水平，并评估其对从疑似疾病进展为复杂性疾病的预后价值。
方法
在2010年至2012年期间，我们前瞻性地纳入了疑似NEC的新生儿。从疑似NEC发作开始，每8小时测量一次I-FABP水平，至少测量48小时，或直至手术。NEC诊断通过放射学或手术确诊。如果NEC导致手术和/或死亡，我们将其定义为复杂性NEC。我们确定了疾病进程和诊断性I-FABP的截断点。
结果
该研究包括37名新生儿（24名男性，13名女性），胎龄28（24-36）周，出生体重1190（570-2400）克。我们发现NEC患者（n = 22）的I-FABPp和I-FABPu水平显著高于其他诊断患者（n = 15）。诊断NEC的截断值为I-FABPp 9 ng/mL和I-FABPu 218 ng/mL，相应的似然比（LRs）分别为5.6（95% CI 0.89-35）和5.1（95% CI 0.73-36）。症状发作后的前8小时I-FABP水平最高，并随时间逐渐下降。复杂性疾病的截断值为I-FABPp 19 ng/mL和I-FABPu 232 ng/mL，LRs分别为10（95% CI 1.6-70）和11（95% CI 1.6-81）。
结论
血浆和尿液中的I-FABP水平均可在出现提示NEC的诊断性放射学征象之前特异性识别早产儿的NEC。此外，连续测量I-FABP可准确预测复杂性疾病的发展。
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