Department of Neonatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark.
Pediatr Res. 2021 Jan;89(1):127-133. doi: 10.1038/s41390-020-0871-0. Epub 2020 Apr 4.
Immature gut motility in preterm neonates may be a risk factor for necrotizing enterocolitis (NEC). Using preterm pigs as a model for infants, we hypothesized that intestinal dysmotility precedes NEC development.
Eighty-five preterm pigs were fed increasing amounts of milk diets to induce NEC lesions, as detected at autopsy on day 5. Gut transit time was determined on day 4 by x-ray imaging after oral intake of contrast solution.
No clinical or radiological signs of NEC were detected on day 4, but macroscopic NEC lesions were recorded in 59% of pigs (n = 50) on day 5. Relative to pigs without NEC (noNEC, n = 35), pigs with small intestinal lesions (siNEC, n = 18) showed delayed stomach emptying time (StEmpty) and time for contrast to reach cecum (ToCecum) already on day 4. Pigs with lesions only in colon (coNEC, n = 20) showed more diarrhea, shorter ToCecum time, but longer small intestinal emptying time (SiEmpty). ToCecum time predicted siNEC and coNEC lesions with a receiver-operator characteristic area under the curve of 78-81%.
Region-dependent changes in gut transit time is associated with early NEC development in preterm pigs. How gut dysmotility is related to NEC in preterm infants requires further investigations.
Using preterm pigs as a model for preterm infants, we show that gut transit time, using serial x-ray contrast imaging, was changed in individuals with NEC-like lesions before they showed the typical radiological signs of NEC. Thus prolonged transit time across the entire gut was recorded when NEC lesions appeared in the small intestine but not when lesions were detected only in the colon. Until now, recordings of food transit have mainly investigated changes in the upper gut. Using serial x-rays, this study describes food transit across the entire gut and documents a region-dependent effect of NEC lesions on gut transit changes in preterm individuals. The findings provide proof of concept for use of x-ray contrast imaging as a tool to monitor gut transit in preterm pigs as models for infants. Delayed passage across the entire gut may be an early sign of small intestinal NEC, at least in pigs. More studies are needed to confirm relations in infants. In the future, it might be possible to use x-ray contrast imaging in preterm infants to better understand gut motility in relation to early NEC progression and need for medical NEC treatment.
早产儿不成熟的肠道动力可能是坏死性小肠结肠炎(NEC)的一个危险因素。我们以早产猪作为婴儿模型,假设肠道动力障碍先于 NEC 发展。
85 只早产猪通过喂养逐渐增加的牛奶饮食来诱导 NEC 病变,通过尸检在第 5 天检测到。在第 4 天通过口服造影剂后的 X 射线成像来确定肠道通过时间。
第 4 天没有出现 NEC 的临床或放射学迹象,但第 5 天有 59%(n=50)的猪出现了小肠病变。与没有 NEC 的猪(noNEC,n=35)相比,小肠病变(siNEC,n=18)的猪胃排空时间(StEmpty)和造影到达盲肠的时间(ToCecum)已经延迟。仅结肠有病变(coNEC,n=20)的猪表现出更多的腹泻、更短的 ToCecum 时间,但小肠排空时间(SiEmpty)更长。ToCecum 时间对 siNEC 和 coNEC 病变具有 78-81%的受试者工作特征曲线下面积的预测价值。
早产猪肠道通过时间的区域依赖性变化与早期 NEC 发展有关。肠道动力障碍与早产儿 NEC 的关系需要进一步研究。
我们使用早产猪作为早产儿模型,表明使用连续 X 射线造影成像,在出现类似 NEC 的病变之前,肠道通过时间已经在出现 NEC 样病变的个体中发生改变。因此,当 NEC 病变出现在小肠但不在结肠时,整个肠道的通过时间都延长了。到目前为止,食物通过的记录主要集中在对上消化道的改变上。本研究使用连续 X 射线描述了整个肠道的食物通过,并记录了 NEC 病变对早产个体肠道通过时间变化的区域依赖性影响。这些发现为使用 X 射线造影作为监测早产猪肠道通过的工具提供了概念验证,这些猪作为婴儿模型。整个肠道的延迟通过可能是小肠 NEC 的早期迹象,至少在猪中是这样。需要更多的研究来证实婴儿的相关性。将来,在早产儿中使用 X 射线造影成像来更好地了解肠道动力与早期 NEC 进展和 NEC 治疗需求的关系是有可能的。