Increased incidence of necrotizing enterocolitis in premature infants born to HIV-positive mothers

OBJECTIVE: To examine if being born to an HIV-positive mother may increase the risk of necrotizing enterocolitis in premature infants. DESIGN: Case-control study. SETTING: Neonatal unit of a level 3 perinatal centre. METHODS:: Over a period of 8.5 years, all cases of necrotizing enterocolitis occurring in premature infants admitted to the neonatal unit were identified. For each case, two controls were retrospectively chosen that matched for postmenstrual age at birth, intrauterine growth and year of birth. Perinatal characteristics were studied in all infants. MAIN RESULTS: There were 79 cases of necrotizing enterocolitis, which were compared with 158 controls. Using multivariate analysis, multiple pregnancy [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.23-4.25; P = 0.009], abnormal umbilical artery velocity (OR, 2.21; 95% CI, 1.08-4.54; P = 0.030), abnormal fetal heart rate (OR, 2.14; 95% CI, 1.05-4.36; P = 0.036) and HIV-positive mother (OR, 6.63; 95% CI, 1.26-34.8; P = 0.025) were significantly more frequent in fetuses who subsequently developed necrotizing enterocolitis. CONCLUSIONS: This preliminary report suggests an association, not previously reported, between maternal HIV-positive status and an increased risk of necrotizing enterocolitis in premature infants. Despite the limitations of this study, we suggest that premature newborn infants of HIV-positive mothers should be monitored very carefully for a possible increased risk of necrotizing enterocolitis.     

Necrotizing enterocolitis in newborns

Necrotizing enterocolitis (NEC) is a neonatal inflammatory bowel disease and is one of the most threatening disease in neonatal gastroenterology. The average incidence of necrotizing enterocolitis 2,4:1000 infants (1 to 10:1000), or about 2.1% (from 1 to 7%) of the total number of children entering the neonatal intensive care unit. The incidence of disease increases with decreasing gestational age at birth. The share of full-term infants accounts for 10-20% of cases of NEC. This paper summarizes the results of own researches and the literature dedicated to this problem.     

Rotavirus-Associated Necrotizing Enterocolitis After Cardiac Catheterization in Infants

Necrotizing enterocolitis is common in preterm and low birth weight infants but rare beyond the neonatal period. Various infectious agents including bacterial and viral organisms have been implicated in its pathogenesis. Rotavirus has recently been shown to be associated with necrotizing enterocolitis. In this report we describe two infants with congenital cardiac disease who developed fulminating necrotizing enterocolitis after cardiac catheterization. Both infants were beyond the newborn period and developed enterocolitis during an epidemic of rotaviral infection. We postulate a relationship between rotavirus infection and the development of necrotizing enterocolitis in older infants with congenital heart disease after cardiac catheterization.     

Neonatal necrotizing enterocolitis Inflammatory bowel disease of the newborn

Neonatal necrotizing enterocolitis is the most common serious gastrointestinal disorder encountered in neonatal intensive care units. It is a major cause of morbidity and mortality in the newborn, particularly in premature infants. Consistent risk factors are birth weight and prematurity. Polycythemia and hyperviscosity altering blood flow and infectious agents are also implicated. Clinical findings include abdominal distention and diarrhea, and systemic symptoms such as apnea, acidosis, and lethargy. Pneumatosis intestinalis can be demonstrated radiographically. Mucosal ulcerations, hemorrhage, and thrombosis occur early, followed by inflammatory changes. Later still necrosis develops. Ischemia, infection, and enteral feedings are suspected to be involved in the pathophysiology. Eicosanoids, especially thromboxane, platelet-activating factor, and leukotrienes are likely mediators.     

Neonatal necrotizing enterocolitis

Neonatal necrotizing enterocolitis is the most common serious gastrointestinal disorder encountered in neonatal intensive care units. It is a major cause of morbidity and mortality in the newborn, particularly in premature infants. Consistent risk factors are birth weight and prematurity. Polycythemia and hyperviscosity altering blood flow and infectious agents are also implicated. Clinical findings include abdominal distention and diarrhea, and systemic symptoms such as apnea, acidosis, and lethargy. Pneumatosis intestinalis can be demonstrated radiographically. Mucosal ulcerations, hemorrhage, and thrombosis occur early, followed by inflammatory changes. Later still necrosis develops. Ischemia, infection, and enteral feedings are suspected to be involved in the pathophysiology. Eicosanoids, especially thromboxane, platelet-activating factor, and leukotrienes are likely mediators.     

Congenital thyrotoxicosis in premature infants

OBJECTIVES: Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex. DESIGN AND PATIENTS: The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays. RESULTS: Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25--36 week) and median B Wt was 1.96 kg (0.50--2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1--16 days) and mean age at commencement of treatment was 12 days (7--26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Four became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supple-mentation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort. CONCLUSIONS: This is a large series of extremely small and premature infants with neonatal thyro-toxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme low birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.     

Neonatal Nosocomial Infection Surveillance: Incidences by Site and a Cluster of Necrotizing Enterocolitis

Summary Nosocomial infection (NI) was prospectively studied in hospitalized neonate during a 10-month period. The Centers for Disease Control (CDC) criteria (some specified for neonates) were used for surveillance. Forty-nine of 677 infants experienced 73 episodes of NI. The overall incidence was 10.8 NI/100 patients and 6.5 NI/1,000 patient days. The average monthly NI number did not correlate with patient load. Very low birth weight (VLBW) infants showed a higher NI incidence (81.8 NI/100 patients and 11.1 NI/1,000 patient days), also elevated if adjusted for their inherently longer neonatal intensive care unit (NICU) stay. The most common NI sites in the VLBW stratum were sepsis and necrotizing enterocolitis (NEC), the latter occurring in a seasonal cluster. It can be concluded that surveillance for NIs should focus on VLBW infants and include the evaluation of NEC, as it behaves like a nosocomial disease. Received: March 2, 1999 · Revision accepted: July 1, 1999     

新生儿低血糖高危因素分析

目的探讨引起新生儿低血糖发生的高危因素及临床特点和预后,为临床诊治及预防提供依据。方法对1000例住院的新生儿的血糖进行常规监测,对确诊的105例低血糖患儿的临床资料进行统计、分析。结果早产儿、足月小于胎龄儿、出生时有窒息史、喂养困难、感染、高胆红素血症、糖尿病母亲娩出的新生儿为新生儿低血糖高危因素。出院后随访5例有运动障碍和智力异常。结论对于早产及足月小于胎龄儿、潜在感染、围生期窒息、喂养困难等有低血糖高危因素的新生儿应严密监测血糖,早开奶,加强喂养,必要时静脉补充,早期诊断和治疗是防止低血糖脑损伤及脑发育障碍的关键。     

Severe Upper Gastrointestinal Bleeding in Healthy Full-Term Neonates

Severe upper gastrointestinal bleeding is unusual in newborns, and is usually seen in sick premature infants. We report on three healthy full-term neonates who, after uneventful deliveries, presented with profuse bleeding in the first 48 h of life. Two infants had duodenal ulcers and one had diffuse hemorrhagic gastritis. All three patients responded to conservative medical therapy and have shown no recurrence of symptoms during a follow-up period of 1–4 yr.     

Distal intramural spread in adenocarcinoma of the lower third of the rectum treated with total rectal resection and coloanal anastomosis

PURPOSE: This study was designed to evaluate the frequency of microscopic distal intramural spread in rectal adenocarcinoma and its correlation to other histopathologic prognostic factors. METHODS: We examined 55 patients with adenocarcinomas of the lower one-third of the rectum and measured the extent of distal intramural spread in the submucosa and/or muscular layer in comparison with Dukes Stage, diameter of tumor, distance of distal margin of resection from tumor, depth of infiltration into perirectal adipose tissue, nodal status, neoplastic infiltration of lymphatic vessels, blood vessels, and nervous branches. RESULTS: Distal intramural spread was found in 40 percent of patients, 77 percent of whom had advanced tumors with nodal metastases. Distal intramural spread appeared to be strictly related to tumor size (superior to 40 mm), infiltration of the perirectal adipose tissue, multiple positive lymph nodes, presence of neoplastic emboli in the intramural lymphatic vessels, and neoplastic invasion of the nervous branches. Local recurrence occurred in one Dukes Stage B patient with a positive distal margin of resection and in four patients with a negative distal margin of resection: three Dukes Stage C and one Dukes Stage B patients with neoplastic involvement of the circumferential margin of resection of the mesorectum. CONCLUSION: These preliminary data suggest that distal intramural spread may carry little importance in determining local recurrence of rectal adenocarcinoma.Supported by Associazione Italiana Ricerca sul Cancro.     

Colonoscopic perforations

Since its introduction into clinical medicine, flexible fiberoptic colonoscopy has had a great impact on diagnosis and management of diseases of the colon and rectum. There are three mechanisms responsible for colonoscopic perforation: specifically, mechanical perforation directly from the colonoscope or a biopsy forceps, barotrauma from overzealous air insufflation, and, finally, perforations that occur during therapeutic procedures. Perforation of the colon, which requires surgical intervention more frequently than bleeding, occurs in less than 1 percent of patients undergoing diagnostic colonoscopy and may be seen in up to 3 percent of patients undergoing therapeutic procedures such as polyp removal, dilation of strictures, or laser ablative procedures. Management of colonic perforation secondary to colonoscopy remains a controversial issue in that it can be effectively managed by operative and nonoperative measures. If a perforation does occur, signs and symptoms that the patient will experience will be related to both the size and site of the perforation, adequacy of the bowel preparation, amount of peritoneal soilage, underlying colonic pathology (where a thin walled colon from colitis or ischemia, for example, may result in a larger perforation than a healthy colon), and, finally, overall clinical condition of the patient. Radiology often establishes diagnosis. Plain films of the abdomen and an upright chest x-ray may reveal extravasated air confined to the bowel wall, free intraperitoneal air, retroperitoneal air, subcutaneous emphysema, or even a pneumothorax. A localized perforation may demonstrate lack of pneumoperitoneum. Some surgeons recommend surgery for all colonoscopic perforations; however, there does appear to be a role for conservative management in a select group of patients such as those with silent asymptomatic perforations and those with localized peritonitis without signs of sepsis that continue to improve clinically with conservative management. Finally, conservative management works well in those patients with postpolypectomy coagulation syndrome. Surgery is most definitely indicated in the presence of a large perforation demonstrated either colonoscopically or radiographically and in the setting of generalized peritonitis or ongoing sepsis. The presence of concomitant pathology at time of colonoscopic perforation such as a large sessile polyp likely to be a carcinoma, unremitting colitis, or perforation proximal to a nearly obstructing distal colonic lesion may force immediate surgery. Finally, in the patient who deteriorates with conservative management, one should proceed to surgery.     

Prospective Surveillance of Nosocomial Infections in a Swiss NICU: Low Risk of Pneumonia on Nasal Continuous Positive Airway Pressure?

Abstract Background: This study assessed the rate of invasive nosocomial infections in very low birth weight (VLBW) ≤ 1,500 g infants in a Swiss university hospital neonatal intensive care unit (NICU). Device–association and devicerelated infection rates were prospectively evaluated. Patients and Methods: From October 1999 to September 2000, 76 hospitalized neonates with VLBW were included, plus 60 neonates > 1,500 g, who had received a central venous or umbilical catheter, or assisted ventilation. Nosocomial infections (sepsis, pneumonia, necrotizing enterocolitis [NEC]) were defined according to Centers for Disease Control (CDC) recommendations with slight modifications and their rates measured longitudinally. Results: Among VLBW neonates, 16 nosocomial infections for an overall infection rate of 6 per 1,000 patient days were found. Infants with infection were of lower birth weight, a greater proportion was male, received lipid infusions, and on average had a higher severity of illness (CRIB) score. Interestingly, the ventilator–associated pneumonia (VAP) rate (12.5/1,000 ventilator days) seemed significantly higher than the pneumonia rate during nasal continuous positive airway pressure (NCPAP) treatment (1.8/1,000 NCPAP days; p = 0.04). The sepsis rate associated with peripheral catheters almost equaled the central line–associated rate, although numbers for both device–related infections were small. Conclusion: Further studies are needed to confirm the observation that the NCPAP–associated pneumonia rate might be lower than the VAP rate in VLBW infants, as well as to confirm the second observation that the sepsis rates on peripheral catheters compared to central venous catheters might be almost equal in VLBW infants. Reducing the exposure to ventilation via endotracheal tube, but not using peripheral as opposed to central catheters, might reduce the incidence of device–associated infection in this patient population. This paper is dedicated to the founders of the Walter Marget Foundation, D. Adam and F. Daschner, in gratitude for their support of the training in infectious diseases.     

Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection

PURPOSE: The aim of this study was to describe our experiences of surgical removal of inflamed bowel in cytomegalovirus enterocolitis. METHODS: Eight homosexual males with a mean age of 41 years (range, 29–59 years) and a mean CD4 count of 21×10 ⁶/1 (1–60× 10⁶/1)with advanced human immunodeficiency virus infection and severe cytomegalovirus enterocolitis were treated with ileocecal resection (4 patients) or right-sided hemicolectomy (4 patients). Symptoms were lower abdominal pain, severe diarrhea, fever, and weight loss, unrelieved by anticytomegalovirus therapy. Radiologic examination showed that ulcerative inflammation was limited to the right colon and terminal ileum. Microscopic examination confirmed the cytomegalovirus enterocolitis. Intermittent cytomegalovirus treatment, usually with foscarnet for 10 to 14 days every 4 to 6 weeks was given postoperatively. RESULTS: Two minor postoperative complications occurred: a lesser wound infection and a moderate bleeding from the abdominal wound edges. One patient died after three weeks because of gastrointestinal bleeding from an ulcerating Kaposi's sarcoma lesion and another patient died from unrelated causes three weeks after discharge from the hospital. The remaining 6 patients experienced complete or partial palliation of the abdominal symptoms for a mean of 14 months (range, 5–35 months) until death or the end of observation time. One patient is still alive two years after the operation. The overall mean survival was 12 months (range, 0.5–35 months). Recurrent or persistent symptoms and/or signs of cytomegalovirus enterocolitis occurred in four patients after a mean of seven months. CONCLUSION: Resection of inflamed bowel combined with postoperative anticytomegalovirus treatment leads to excellent palliation and a relatively favorable survival in AIDS patients with cytomegalovirus enterocolitis.     

Necrotizing enterocolitis： A multifactorial disease with no cure

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.     

Clostridium difficile isolation in neonates in a special care unit. Lack of correlation with necrotizing enterocolitis

The stools of 78% of 45 infants in a Special Care Baby Unit yielded Clostridium difficile on culture, and in 67% of these it was possible to detect C. difficile toxin by means of a tissue culture technique. The stools of six of the seven infants with necrotizing enterocolitis were positive for C. difficile, but neither of the two most severely affected contained C. difficile toxin. The incidence of C. difficile isolation was similar in infants treated by exchange transfusion, those treated with antibiotics, those of low birth weight, and those with respiratory distress. The serum of only 2 of 28 infants and 1 of 20 mothers contained a neutralizing factor to C. difficile toxin. The present study does not support a role for C. difficile in neonatal disorders and in particular necrotizing enterocolitis. The reason for the apparent tolerance of the neonatal bowel to C. difficile toxin remains to be explained.     

Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period

Pregnenolone (Preg) and 17-hydroxypregnenolone (17OH-Preg) are marker steroids that are elevated in the 3beta-hydroxysteroid-dehydrogenase-II deficiency form of congenital adrenal hyperplasia. The aim of this study was to establish normative data for both steroids in healthy preterm (28-33 and 34-37 wk gestation) and full-term infants, because reference values for the early neonatal period do not exist. At delivery, the main source of Preg is the placenta, because the highest levels were found in the retroplacental space (median, 141.31 nmol/liter), with no significant difference between preterm and full-term pregnancies. The fetal adrenals provide most of the circulating 17OH-Preg in full-term neonates, as demonstrated by a marked arteriovenous gradient in cord blood (40.96 nmol/liter vs. 10.77 nmol/liter). 17OH-Preg levels in the umbilical arteries were significantly lower in premature infants than in full-term infants (8.06 nmol/liter vs. 40.96 nmol/liter). During the first 2 postnatal weeks, Preg concentrations showed a rapid and significant fall in early preterm infants [95.78 nmol/liter (0 h) to 36.69 nmol/liter (d 14)] as well as in full-term infants [66.62 nmol/liter (0 h) to 14.81 nmol/liter (d 6)]. In addition, a significant fall in 17OH-Preg levels was found in full-term neonates [40.96 nmol/liter (0 h) to 11.32 nmol/liter (d 6)]. After 12 h, significantly higher levels for Preg and 17OH-Preg were found in early preterm infants (98.01 nmol/liter and 69.13 nmol/liter), compared with full-term neonates (36.29 nmol/liter and 28.55 nmol/liter, P < 0.05), reflecting the increased fetocortical activity as a response to the stress of delivery in the prematures. With these longitudinal data, it is now possible to confirm or exclude the diagnosis of 3beta-hydroxysteroid-dehydrogenase-II deficiency within the first postnatal week.     

Neonatal wound dehiscence and the subsequent healing process: a case study

Many neonates require abdominal surgery for a variety of reasons, including necrotizing enterocolitis (NEC). Secondary complications of abdominal surgery include alterations in skin integrity and potential wound dehiscence. These alterations may actually worsen when treated with products "traditionally" used postoperatively. The author simultaneously utilized basic wound care products with currently recognized therapies in managing a 29-week premature infant who experienced dehiscence secondary to bowel repair. By utilizing the correct products and incorporating the principles of moist wound healing and occlusion, this Stage III/IV wound, measuring 12 cm x 3 cm, closed within 35 days of dehiscence. A team-oriented and coordinated approach proved that wounds can, and will, improve, even in this fragile population.     

Thrombocytopenia in the newborn

Thrombocytopenia is the most common hemostatic abnormality in sick newborn infants. Although many conditions may be associated with neonatal thrombocytopenia, low platelet counts in the first few days of life are often caused by fetomaternal problems, whereas thrombocytopenia developing after the third day is usually secondary to sepsis or necrotizing enterocolitis. Despite the frequency of thrombocytopenia in sick neonates, the underlying kinetic mechanisms are not always clear. The commonly accepted theories of decreased platelet production or increased consumption are being scrutinized in the light of new evidence. Thrombopoietin and interleukin-11 are being investigated to unravel the complex pathophysiology of thrombocytopenia in neonates and they are also being explored as potential therapeutic agents. Guidelines for platelet transfusions continue to be variable and controversial.     

Diagnostic value of C-reactive protein in acute appendicitis

Serum C-reactive protein was measured in 56 patients hospitalized with a suspected diagnosis of acute appendicitis. Based on these determinations, four groups of patients were defined: Group A=26 patients with acute appendicitis who had a C-reactive protein level higher than 2.5 mg/dl. Group B=4 patients with a C-reactive protein level lower than 2.5 mg/dl who, after surgery based on a presumed diagnosis of acute appendicitis, were found to have a normal appendix. Group C=22 patients with nonspecific abdominal pain, 18 (72 percent) of whom had an elevated C-reactive protein level, although in only 4 (7.1 percent) were these levels higher than 2.5 percent mg/dl. Group D=4 patients who had diseases other than acute appendicitis. It is concluded that an increase in C-reactive protein levels to more than 2.5 mg/dl is not a definite indicator of acute appendicitis. However, if the C-reactive protein level in blood drawn 12 hours after the onset of symptoms is less than 2.5 mg/ dl, acute appendicitis can be excluded.     

Evaluation of CD11b expression on peripheral blood neutrophils for early detection of neonatal sepsis

Neonatal sepsis is a disease of infants who are less than 1 month of age. These infants are clinically ill, and their blood culture are positive for bacteria. The reported incidence of neonatal sepsis for all infants is 1 to 10 per 1000 live births. The mortality rate is 4.2-26%. The clinical signs are not specific and diagnosis of neonatal sepsis is one of the most difficult tasks in clinical medicine. The aim of this work was determination of CD11b sensitivity and specificity for early detection of neonatal sepsis. We studied 65 neonates with gestational age of 27 to 38 weeks who were suspected for sepsis within the 28 days of life. Whole blood was obtained from neonates to determine CD11b expression on peripheral blood neutrophils by flow cytometry. C-Reactive protein (CRP) was measured qualitatively. Neonates were divided into two groups. Classification was based on the result of the blood culture. In the sepsis group all of the neonates (n=8) showed positive blood culture and clinical symptoms. In the suspected group (n=57) the neonates showed clinical signs but blood cultures were negative. Sensitivity and specificity of CD11b were 75%, 100% respectively. Also positive and negative predictive values of CD11b were 100% and 86% respectively. Results of present study and previous studies showed that measurement of neutrophil surface markers can be useful for diagnosis of infection in the early phases. Also, the quantitative measurement of CRP in addition to CD11b further enhances the ability to diagnose infections and improves sensitivity and negative predictive value by 100%.