Impact of development of the gastrointestinal tract on infant feeding

We have described the developmental pattern of the gastrointestinal tract under optimal conditions (i.e., low risk pregnancy and normal labor and delivery at term). The tissues do not develop simultaneously, and morphologic and functional development are not concurrent. An important consideration is the effect of suboptimal or even adverse conditions on the developmental sequence and attainment of maturity. Malnutrition during both the prenatal and postnatal periods may restrict the morphologic and biochemical development of the gastrointestinal tract. Dietary modifications have been shown to alter the developmental pattern of intestinal and pancreatic enzymes in animal models. Drugs and hormonal therapy given during pregnancy and early infancy have been known to cause developmental defects, but the specific effects on the gastrointestinal tract have not been evaluated. For further understanding of digestibility of nutrients and absorption in the perinatal period, these departures from the normal development of the gastrointestinal tract and the mechanisms by which these potential effects occur remain to be described. In view of these undetermined factors, in the case of intolerance or unavailability of milk from the natural mother, feedings should be individualized, with attention to direct measurement of enzyme concentrations, balance studies, or both, especially in the case of extreme prematurity or unusual requirements.     

Gastrointestinal maturation and implications for infant feeding

The level of gastrointestinal (GI) maturity of an individual infant is a major determinant of whether the infant will be able to meet nutritional needs by sole use of the GI tract or if parenteral means will be necessary. The GI tract is not only an organ for digestion and absorption of nutrients; it also performs major endocrine, neural and immunologic functions. In this review, anatomic, functional and biochemical development will be described and related to means by which enteral nutrition can be used in the prematurely born infant to optimize health and prevent disease.     

Unusual variations of gastrointestinal smooth muscle abnormalities associated with chronic intestinal pseudo-obstruction

The clinicopathological spectrum of gastrointestinal (GI) smooth-muscle abnormalities associated with chronic intestinal pseudo-obstruction (CIPO) includes numerous heterogeneous conditions that are often ill-defined and poorly understood. Primary GI smooth-muscle abnormalities include familial and sporadic forms. Secondary involvement of GI smooth-muscle may result from associated GI and systemic conditions, but is less frequent than in adults. This study documents the clinicopathological findings observed in 12 South African patients with unusual forms of visceral smooth-muscle abnormalities not conforming to the diagnostic criteria of known primary visceral myopathies at the Tygerberg and Red Cross Childrens' Hospitals over a 14-year period (July 1985 through January 1999). Congenital muscle defects occurred in 5 patients where layers of bowel-wall muscle were absent or attenuated. Idiopathic fibrosis and ultrastructural features of perinuclear and mitochondrial vacuolisation were noted in 2 patients. A 21-year-old female with long-standing pseudo-obstruction demonstrated diminished immunohistochemical expression of enteric alpha-smooth-muscle actin without associated muscular degeneration or fibrosis. A secondary complication of dermatomyositis (bowel perforation) occurred twice in 1 patient. In 3 further patients (1 each with anorectal malformation, long-segment Hirschsprung's disease, and intestinal neuronal dysplasia), muscle fibrosis appeared during progression of the pre-existing disease. Visceral myopathies are poorly understood conditions that may present with CIPO. Unusual variations occur that do not conform to the usual recognised histological patterns. Secondary involvement may also be more common than anticipated in children. The challenge to further understanding these uncommon conditions lies in timely diagnosis and identification of early, subtle signs. Optimal and extensive application of various diagnostic modalities, including the development of new diagnostic tools, is of considerable importance in identifying hitherto unexplained CIPO due to GI smooth-muscle abnormalities.     

Enteral administration of hematopoietic growth factors in the neonatal intensive care unit

GI trophic factors have been identified that influence the prenatal and postnatal growth and development of the GI tract. Systemically as well as enterally administered growth factors can stimulate GI growth and maturation, suggesting that trophic factors in the serum of neonates can modulate GI growth via receptors on the serosal membranes of enterocytes. GI trophic factors can be synthesized endogenously or provided prenatally in amniotic fluid and postnatally in human milk.
GI trophic factors in human milk play an important role in regulating the adaptive functional changes that accompany the transition to postnatal enteral feedings. Although human milk growth factors are not essential for infant survival, the elevated risk of GI-related illnesses in formula-fed compared with human milk-fed infants suggests that bioactive compounds in human milk contribute to the protective effects of human milk feedings (13).
GI trophic factors have the potential to be used therapeutically to enhance GI maturation and repair following injury. These applications may be particularly useful in the premature or postsurgical infant. Several issues require further research, including: (i) the efficacy of oral versus systemic administration; (ii) characterization of the complex interactions among the various growth factors; (iii) the effect of exogenously administered growth factors on endogenous production of that factor, its receptor or other growth factors; (iv) the effect of growth factors upon tissues not directly associated with the GI tract; and (v) the determination of safe and effective limits. Significant advances in feeding strategies to reduce feeding intolerance in the neonate are likely to occur with the application of these principles in clinical neonatology.     

Effects of enterally administering granulocyte colony-stimulating factor to suckling mice

Gastrointestinal (GI) tract development is influenced by multiple growth factors, some of which are delivered directly to the GI lumen, as they are swallowed constituents of amniotic fluid, colostrum, and milk. Granulocyte colony-stimulating factor (G-CSF), traditionally known as a granulocytopoietic growth factor, is an example of one such factor. However, it is not clear whether the large amounts of G-CSF that are normally swallowed by the fetus and neonate have systemic effects on circulating neutrophils or local effects in the developing intestine. To assess this, we administered either active or heat-denatured (control) recombinant human G-CSF to 5- to 7-d-old C57BL/6 x 129SvJ mice. Pups received either a low dose (3 ng) that was calculated to approximate the amount of G-CSF swallowed in utero from amniotic fluid or an isovolemic high dose 100 times larger (300 ng). Oral dosing was performed daily for either 3 or 7 d, after which pups were killed and measurements were made on the blood and the GI tract. Absolute blood neutrophil counts and immature to total neutrophil ratios did not differ from controls in any of the test groups. However, intestinal villus area, perimeter, length, crypt depth, and proliferating cell nuclear antigen index increased significantly among those that were treated with active G-CSF. Thus, in suckling mice, enterally administered G-CSF had no effect on the concentration of circulating neutrophils but had trophic effects on the intestine. We speculate that the G-CSF present in amniotic fluid, colostrum, and milk acts as a topical intestinal growth factor and has little or no granulocytopoietic action.     

Effects of hypoxemia on gastrointestinal blood flow and gastric emptying in the newborn piglet

The effects of severe hypoxemia on gastrointestinal (GI) blood flow and gastric emptying were studied in nine 2- to 4-day-old piglets which were mechanically ventilated while receiving nitrous oxide anesthesia. Each animal was studied during a control period of oxygenation (PaO2 91 +/- 8 torr), 35 min of hypoxemia (PaO2 29 +/- 1 torr), and a recovery period (PaO2 90 +/- 5 torr) (mean +/- SEM). During each study period, the animal received a 10% dextrose test meal with phenol red marker (22 ml/kg), gastric residual volumes were determined at 10-min intervals over 30-min study periods using a dye dilution double sampling technique, and GI blood flow (radionuclide-labeled microspheres), O2 delivery, O2 extraction, and O2 consumption were measured at the end of the 30-min period. Hypoxemia resulted in decreased blood flow to the following GI organs: stomach, jejunal and ileal mucosa-submucosa, and colon decreased 62, 31, and 35%, respectively (p less than 0.05). Jejunal and ileal muscularis blood flow remained unchanged. Oxygen delivery and consumption by GI tract decreased 79 and 58%, respectively; whereas oxygen extraction of GI tract increased 115%. Values returned toward baseline levels during the recovery period. The hypoxemic gastric emptying pattern showed significantly greater gastric residuals at 20 min compared to the 10-min value (p less than 0.05). This pattern was different than that observed during control and recovery periods. We conclude that severe hypoxemia results in decreased GI blood flow, tissue oxygenation, and an altered gastric emptying pattern. These observations may have clinical significance for feeding infants following an hypoxemic episode.     

Enteral administration of hematopoietic growth factors in the neonatal intensive care unit

By 20 wk of gestation, the human fetal gastrointestinal (GI) tract morphologically resembles that of the term infant, but functional development is limited before 26 wk. By 30 wk of gestation, the fetus has the capacity for limited digestion and enteral absorption. GI growth and development continue postnatally. Trophic factors, including nutrients, peptides, hormones and growth factors, are recognized as having important influences on the morphology and histology of the developing GI tract. Other trophic factors are important in adaptation and repair following injury. Many such factors are provided in utero via amniotic fluid swallowing and later by human colostrum and milk. CONCLUSION: This review discusses cytokines with known GI trophic effects, either in vitro or in vivo, and focuses on those cytokines that have been used in the neonatal intensive care unit.     

In the critically ill, nothing-by-mouth infant, would enteral administration of simulated amniotic fluid improve feeding tolerance compared with the current practice of no therapy? An evidence-based review

Necrotizing enterocolitis (NEC ) can be a devastating disease in the NIC U population. The current standard of practice of not providing enteral nutrition to the critically ill and the premature infant is thought to result in pathophysiologic changes of the gastrointestinal (GI) tract that may result in the development of NEC. Various methods of preventing or reducing the incidence of NEC in the NIC U have been explored. One such method is the enteral administration of simulated amniotic fluid (SAF). This article compares, contrasts, and reviews the available evidence regarding the use of SAF feedings as a means of reducing GI tract changes associated with nothing-by-mouth (NPO) status.     

Possible Biological Growth Factors in Breast Milk and Postnatal Development of the Gastrointestinal Tract

To investigate as to whether or not biological growth factors known to be present in natural milks could influence postnatal development of Bstrointestinal (GI) tract, tests were made to determine the enteric mucasal, protein and DNA contents, alkaline phosphatase and disaccharidase activities in mongrel puppies at birth and after four days of both mother-reared and artificial reared. Microvilli of the jejunal segment were also investigated histologically by electron microscopy. Similar increases in body weight over the first four days of life were obtained and mucosal protein and DNA contents in the small intestine were greater in the mother-reared animals than in the newborn animals but neither mucosal protein content nor DNA content of the artificially reared animals was different from that of the newborn animals. Alkaline phosphatase activity was greater in both the mother-reared and artificially reared animals than that of the newborn animals. The disaccharidase activities were not different among the three groups. The jejunal microvilli of the mother-reared animals were more elaborately grown in the structure than those of the artificially reared or newborn animals. Therefore, this study demonstrated that the mother rearing over the fmt four days of life resulted in acceleration of the enteric mucosal growth, and the result indicates that breast feeding plays an important role in the development of the GI tract during the neonatal period.     

Down syndrome and the enteric nervous system

Down syndrome (DS) is the most common chromosomal abnormality occurring in humans. Up to 77% of DS children have associated gastrointestinal (GI) abnormalities, which may be structural or functional in nature. Functional disturbances may, in turn, affect the outcome of corrective surgical procedures, prompting to caution. It is becoming clear that the processes affecting the enteric nervous system (ENS) in DS not only affect the micro-anatomy but also nerve function, and there is some histological evidence of ENS variations in both human and DS animal models. This suggests that developmental disorders of the ENS are probably fundamental to the functional GI disturbances encountered in patients with DS. The anomalous brain development, function and resulting intellectual impairment associated with DS appears to result from the genetic imbalance created by the trisomy of chromosome 21. The possible links between the brain, GI and ENS involvement are not as yet entirely clear. Neurotropic factors affecting brain development during embryogenesis are probably interlinked with ENS development, but the precise mechanism of how this occurs has yet to be established. This study explores what is known about the ENS dysfunction in DS and reviews the possible importance of chromosome 21 located and other genes in its etiology. Functional motor disturbances of the esophagus and colon are not uncommon and may be congenital or acquired in nature. The most prominent of these include esophageal dysmotility syndromes (e.g. achalasia, gastroesophageal reflux, dysphagia) as well as a higher incidence of chronic constipation and Hirschsprung's disease (HSCR) (2-15%) occurring in association with DS. Chromosome 21 itself is thought to be the site of a modifier gene for HSCR. Recently identified candidate genetic mechanisms provide unique insights into the genetic background of the neurological and cognitive disorders associated with DS. Although the role of the triplicated chromosome 21 and genetic dosage remain important, the additional role of other chromosome 21 genes in the etiology of ENS developmental anomalies remains undetermined and requires ongoing research.     

Improved gastrointestinal symptom burden after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in kidney transplanted children

Abstract:  It has been shown in adult kidney transplant recipients that a conversion from MMF to EC-MPS significantly reduced the GI related symptom burden. No such study exists on children with GI problems while receiving MMF therapy. Ten paediatric kidney transplant recipients (mean age 14.5 yr, s.d. 4.5) receiving triple immunosuppression (Cyclosporin A or Tacrolimus + MMF + Prednisolone) with severe GI symptoms were converted to an equimolar dose of EC-MPS. The GSRS was completed before and at four wk after the switch, and GFR was determined for a mean period of six months. Values were compared by the paired t-test. Mean GSRS improved significantly after the switch to EC-MPS in all but one patient, from 2.1 (s.d. 0.9) to 1.1 (s.d. 0.6). The differences could be found in all four subscales. Graft function did not change after conversion to EC-MPS. In children with moderate or severe GI symptoms while receiving MMF, conversion to EC-MPS led to significantly reduced GI symptoms.     

Fluoroscopic findings in pediatric eosinophilic esophagitis

Background

Eosinophilic esophagitis (EE) is an inflammatory disorder of the esophagus characterized by symptoms such as dysphagia, food sticking and heartburn. Several fluoroscopic findings have been described in EE, but the frequency of these findings is unknown.

Objective

To identify the frequency of imaging findings in pediatric-age patients with eosinophilic esophagitis.

Materials and methods

A retrospective study was performed evaluating all upper GI and esophagram studies performed between 2000 and 2008 in patients up to age 21 with a pathological diagnosis of EE. In order to be included in the study, the upper GI or esophagram had to be performed either before EE was diagnosed or within 30?days of the diagnosis. Two pediatric radiologists evaluated each study for the presence or absence of multiple findings of EE. The radiology reports from the time of the study were then read to establish a concurrent diagnosis of esophageal dysmotility or gastroesophageal reflux. Finally, the hospital electronic medical record was evaluated to obtain demographic and pathology information.

Results

Of the 579 patients with biopsy-proven EE, 107 (18%) were included in the study and underwent a total of 112 upper GI or esophagram examinations. The most common finding on these examinations was a normal esophagus (58/112; 52%) followed by gastroesophageal reflux (21/112; 19%) and irregular contractions (17/112; 15%). Less frequent findings included strictures, dysmotility, mucosal irregularity, esophageal rings and filling defects.

Conclusion

Fluoroscopic studies are not a sensitive method to diagnose EE because nearly half of the studies are normal. Findings that have been described in the setting of EE such as food impaction, a ringed esophagus, a small-caliber esophagus and esophageal stricture do not occur with a high enough frequency to reliably make a diagnosis.     

Vedolizumab for pediatric patients with gastrointestinal acute graft-versus-host-disease

Vedolizumab, an anti-α4β7 integrin monoclonal antibody, impairs homing of T-cells to the gastrointestinal (GI) endothelium and acts as a gut-selective anti-inflammatory agent. Recent reports of the efficacy of vedolizumab in treating lower GI acute graft-versus-host disease (aGVHD) are promising, but experience in children is scarce. We present a cohort of 13 pediatric patients who were treated with vedolizumab for GI aGVHD. Ten of the patients were treated for steroid-refractory disease, out of which, six suffered from severe (stage 3 or 4) GI disease before the first dose of vedolizumab. In the other three patients, vedolizumab was introduced early in the disease course. Median time between GI GVHD onset to vedolizumab treatment was 23 days (range 7–59 days), with a median of 3 doses (range 1–5) per patient. GI GVHD staging was evaluated at various time points after the first vedolizumab dose, showing improvement in nine of the 13 patients. After a median follow-up time of 13 months (range 6–34 months), eight patients completely recovered, two had ongoing chronic colitis, and three patients died. During the vedolizumab treatment period, 38 infectious episodes were noted, most of them GI related. The unique activity profile of vedolizumab makes it an appealing treatment option for lower GI aGVHD, but caution for concurrent infections is warranted.     

Gastrointestinal blood flow and O2 uptake in piglets: recovery from hypoxemia

Gastrointestinal (GI) blood flow, O2 transport, and O2 uptake were measured during recovery from severe hypoxemia in newborn piglets. Hypoxemia was induced by lowering the inspired O2 concentration to 0.05 for 15 min. This resulted in an 82% decrease in GI O2 uptake. Recovery measurements were obtained 5 and 65 min after restoration of normoxia. During early recovery (5 min), GI O2 uptake increased above prehypoxemia baseline, presumably to "repay" the O2 deficit incurred during hypoxemia. This was mediated by an increase in the arteriovenous O2 content difference, as GI blood flow did not increase above prehypoxemia baseline. During late recovery (65 min), GI blood flow, O2 delivery, and arteriovenous O2 content difference decreased below prehypoxemia baseline. This resulted in a 52% decrease in GI O2 uptake below prehypoxemia baseline. Therefore, early recovery was characterized by an appropriate increase in GI O2 uptake; however, late recovery was characterized by a significant reduction in GI O2 transport and uptake. Circulatory homeostasis was not reestablished during the late recovery period.     

Application of the mouse exo utero development system in the study of developmental biology and teratology

The mouse exo utero development system is useful for analyzing the roles of molecules or interactions between tissues in the histogenesis of organs after the mid-gestational period. In the article presented here, we review the mouse exo utero development system and its specific modifications depending on different purposes as well as its advantages over and limitations compared to other systems in the study of developmental biology and teratology.     

Gastrointestinal malignancy in cystic fibrosis

Cystic fibrosis (CF) is a multisystem disease affecting the gastrointestinal (GI) tract as well as the lungs. As survival has increased significantly over the past few decades, complications not seen previously have become apparent. There is an overall increased rate of malignancy in CF, particularly from the GI tract and in the post-transplant population. The most common sites of malignancy are the pancreatico-biliary and digestive tract, as well as an increased rate of testicular cancer. Using an illustrative case of metastatic oesophageal malignancy which initially appeared to be hepatic in origin, we have reviewed the literature surrounding malignancy in CF with a particular focus on the GI tract.     

Stricture of the duodenum and jejunum in an abused child

We report a case of abdominal injury secondary to child abuse in which the child had both a duodenal hematoma and contained perforations of the duodenum and proximal jejunum. These injuries were evaluated by both CT scan and upper gastrointestinal (GI) series. The child's nausea and vomiting persisted despite conservative treatment; after 3 weeks a repeat upper GI series demonstrated high-grade duodenal obstruction. An exploratory laparotomy was performed and a calcified, fibrotic mesentery and strictures in the distal duodenum and proximal jejunum were found. To our knowledge, this unusual complication of blunt abdominal trauma has not been described in association with child abuse. Received: 31 May 1996 Accepted: 16 September 1996     

Neonatal metrizamide gastrointestinal series in suspected necrotizing enterocolitis

The diagnosis of necrotizing enterocolitis (NEC) in neonates may be made by clinical presentation, roentgenographic findings, or a combination of both. Diagnosis leads to immediate treatment including nasogastric suction, parenteral antibiotics, plasma, and close monitoring of clinical, roentgenographic, and laboratory findings. Occasionally, neither the clinical nor plain roentgenographic appearance of an infant allows the diagnosis of NEC to be made or excluded with confidence. In such infants portable isotonic metrizamide gastrointestinal (GI) series were used to help make the decision of whether to begin treatment for NEC or to continue feeding the patient. Of 15 patients examined, two exhibited signs of NEC and were successfully treated medically without GI (tract) sequelae. Twelve neonates had normal results of metrizamide GI series and ten were immediately fed with no GI complication. One of these 12 infants had feedings withheld for several days as a result of a positive blood culture. One infant with severe cardiac and pulmonary disease had profound adynamic ileus and could not be fed. We have found the metrizamide GI series to be a useful study in neonates suspected of having NEC.     

阿德里装治疗法在脑性瘫痪中应用的研究进展

小儿脑性瘫痪的康复治疗是一个世界性难题,随着现代科技的高速发展,一些新的理念和技术成功应用于脑性瘫痪的康复治疗,其中阿德里装治疗法就是利用太空衣技术,结合密集训练建立的一种脑性瘫痪新疗法,目前在欧美国家临床得到了初步开展。该文重点综述阿德里装治疗法的原理、方法和疗效,为脑性瘫痪治疗提供一种新的康复方法。     

孕期膳食血糖生成指数变化与出生体重及母子胰岛素抵抗水平的关系

目的：探讨超重孕妇孕期膳食血糖生成指数（GI）变化水平与新生儿出生体重及母子胰岛素抵抗水平的关系。方法：选择在江苏省昆山市妇幼保健所及上海市国际和平妇幼保健院参加产检的超重孕妇为研究对象。前瞻性收集孕妇初次产检及孕中期膳食资料,计算GI变化水平（ΔGI）。采用Pearson相关分析ΔGI与新生儿出生体重、孕晚期空腹胰岛素及脐血C肽之间的相关关系,利用多元回归校正混杂因素的影响,进一步分析ΔGI与三者之间的关系。将ΔGI分为4组（<25%、~50%、~75%和＞75%）, 出生体重分为巨大儿、正常体重儿、低出生体重儿3组,应用有序多分类Logistic 回归分析孕期ΔGI和出生体重各分组之间的关系。结果：本文共纳入392名超重孕妇,初诊和孕中期膳食GI平均水平分别为64.4±9.2和63.8±9.5,ΔGI为-0.6±12.7。孕晚期空腹胰岛素平均水平为11.6(7.4~15.8) μU·mL-1。新生儿平均出生体重（3489.7±519.6）g,巨大儿发生率14.4%,脐血C肽的平均水平为0.7(0.4~1.0) ng·mL-1。相关分析并未发现ΔGI与新生儿出生体重、孕晚期空腹胰岛素及脐血C肽之间的关系。多元线性逐步回归分析显示新生儿出生体重与ΔGI、孕期增重、新生儿性别、分娩孕周有关。有序多分类Logistic 回归分析显示,随着孕期ΔGI的增加,新生儿出生体重呈上升趋势（OR=1.54,95% CI:1.06~2.25）。多元回归分析并未发现ΔGI与孕晚期空腹胰岛素、脐血C肽之间的关系。结论：超重孕妇孕期膳食GI变化水平与新生儿出生体重显著相关,与母子胰岛素抵抗水平无关。