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Luo W, Cao H, Hu Y, Liu Z, Yang J, Deng P, Huang S, Huang Q, Wei H. Optimizing nutritional strategies in term NEC and perforation infants after intestinal operation: a retrospective study. Sci Rep 2025; 15:5577. [PMID: 39955353 PMCID: PMC11829962 DOI: 10.1038/s41598-025-90366-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/12/2025] [Indexed: 02/17/2025] Open
Abstract
Necrotizing enterocolitis (NEC) represents a severe condition in infants, with perforation being a particularly critical pathological manifestation. However, there is an absence of guidelines regarding the refeeding of infants recovering from perforation subsequent to NEC. This study aimed to determine the optimal refeeding method for term infants recovering from perforation after NEC. The study encompassed three aspects: the timing of enteral nutrition (EN) resumption, the progression of EN, and the method of EN resumption. Ninety full-term neonates who developed perforation following NEC and underwent surgical intervention were included. These samples were divided into early enteral nutrition (EEN, < 7 days) and late enteral nutrition (LEN, ≥ 7 days) groups based on the timing of EN resumption; faster increase (FI, ≥ 20 ml/kg/d) and slower increase (SI, < 20 ml/kg/d) groups based on the progression of EN; intact protein formula (IPF), special medical formula (SMF, including EHF and AABF), and mixed feeding (MF) groups based on the method of EN resumption. EEN infants had a lower incidence of intestinal stenosis and reoperation (43.5% vs. 77.6%, p = 0.002; 60.9% vs. 82.1%, p = 0.038), and a shorter duration of hospital stay after surgery and parenteral nutrition (PN) than LEN infants (14 days vs. 20 days, p < 0.001; 11 days vs. 17 days, p < 0.001). Faster increasing feed volumes was associated with shorter duration of hospital stay and parenteral nutrition (15 days vs. 20 days, p < 0.001; 14 days vs. 17 days, p < 0.001), but a slower rate of weight gain (0.020 kg vs. 0.129 kg, p < 0.01). The time to repeat NPO in SMF group is shorter than IPF an MF groups (3 days vs. 4 days and 9 days, p = 0.025). Our study demonstrates the beneficial effects of early enteral feeding and fast advancement of feed volumes in term infants with NEC and perforation after surgery, specifically in reducing short-term complications and the duration of hospital stay following surgery and PN. Additionally, this study suggests that IPF and MF significantly contribute to stimulate intestinal adoption recovery.
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Affiliation(s)
- Wen Luo
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Han Cao
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Ya Hu
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Zhenqiu Liu
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Jing Yang
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Pinglan Deng
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Shan Huang
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Qianjing Huang
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Hong Wei
- Department of Neonatology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
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van Gorp C, de Lange IH, Hütten MC, López-Iglesias C, Massy KRI, Kessels L, Knoops K, Cuijpers I, Sthijns MMJPE, Troost FJ, van Gemert WG, Spiller OB, Birchenough GMH, Zimmermann LJI, Wolfs TGAM. Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies. Int J Mol Sci 2024; 25:4000. [PMID: 38612809 PMCID: PMC11011967 DOI: 10.3390/ijms25074000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 03/29/2024] [Accepted: 04/01/2024] [Indexed: 04/14/2024] Open
Abstract
Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development.
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Affiliation(s)
- Charlotte van Gorp
- Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands; (C.v.G.); (M.C.H.); (K.R.I.M.); (L.K.); (L.J.I.Z.)
| | - Ilse H. de Lange
- Department of Pediatrics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, The Netherlands;
| | - Matthias C. Hütten
- Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands; (C.v.G.); (M.C.H.); (K.R.I.M.); (L.K.); (L.J.I.Z.)
- Neonatology, Department of Pediatrics, University Hospital RWTH Aachen, 52074 Aachen, Germany
| | - Carmen López-Iglesias
- Microscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6211 LK Maastricht, The Netherlands; (C.L.-I.); (K.K.)
| | - Kimberly R. I. Massy
- Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands; (C.v.G.); (M.C.H.); (K.R.I.M.); (L.K.); (L.J.I.Z.)
| | - Lilian Kessels
- Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands; (C.v.G.); (M.C.H.); (K.R.I.M.); (L.K.); (L.J.I.Z.)
| | - Kèvin Knoops
- Microscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6211 LK Maastricht, The Netherlands; (C.L.-I.); (K.K.)
| | - Iris Cuijpers
- Food Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 5911 BV Venlo, The Netherlands; (I.C.); (M.M.J.P.E.S.); (F.J.T.)
| | - Mireille M. J. P. E. Sthijns
- Food Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 5911 BV Venlo, The Netherlands; (I.C.); (M.M.J.P.E.S.); (F.J.T.)
| | - Freddy J. Troost
- Food Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 5911 BV Venlo, The Netherlands; (I.C.); (M.M.J.P.E.S.); (F.J.T.)
| | - Wim G. van Gemert
- Department of Surgery, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, The Netherlands;
| | - Owen B. Spiller
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XW, UK;
| | - George M. H. Birchenough
- Department of Medical Biochemistry, Institute of Biomedicine, University of Gothenburg, 40530 Gothenburg, Sweden;
| | - Luc J. I. Zimmermann
- Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands; (C.v.G.); (M.C.H.); (K.R.I.M.); (L.K.); (L.J.I.Z.)
| | - Tim G. A. M. Wolfs
- Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands; (C.v.G.); (M.C.H.); (K.R.I.M.); (L.K.); (L.J.I.Z.)
- Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands
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Solis-Garcia G, Pierro A, Jasani B. Laparotomy versus Peritoneal Drainage as Primary Treatment for Surgical Necrotizing Enterocolitis or Spontaneous Intestinal Perforation in Preterm Neonates: A Systematic Review and Meta-Analysis. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1170. [PMID: 37508667 PMCID: PMC10378122 DOI: 10.3390/children10071170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/30/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023]
Abstract
AIM to systematically review and meta-analyze the impact on morbidity and mortality of peritoneal drainage (PD) compared to laparotomy (LAP) in preterm neonates with surgical NEC (sNEC) or spontaneous intestinal perforation (SIP). METHODS Medical databases were searched until June 2022 for studies comparing PD and LAP as primary surgical treatment of preterm neonates with sNEC or SIP. The primary outcome was survival during hospitalization; predefined secondary outcomes included need for parenteral nutrition at 90 days, time to reach full enteral feeds, need for subsequent laparotomy, duration of hospitalization and complications. RESULTS Three RCTs (N = 493) and 49 observational studies (N = 19,447) were included. No differences were found in the primary outcome for RCTs, but pooled observational data showed that, compared to LAP, infants with sNEC/SIP who underwent PD had lower survival [48 studies; N = 19,416; RR 0.85; 95% CI 0.79-0.90; GRADE: low]. Observational studies also showed that the subgroup of infants with sNEC had increased survival in the LAP group (30 studies; N = 9370; RR = 0.82; 95% CI 0.72-0.91; GRADE: low). CONCLUSIONS Compared to LAP, PD as primary surgical treatment for sNEC or SIP has similar survival rates when analyzing data from RCTs. PD was associated with lower survival rates in observational studies.
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Affiliation(s)
- Gonzalo Solis-Garcia
- Division of Neonatology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
- Department of Pediatrics, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
- Department of Pediatrics, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Agostino Pierro
- Department of Pediatrics, University of Toronto, Toronto, ON M5S 1A1, Canada
- Department of Surgery, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
| | - Bonny Jasani
- Division of Neonatology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
- Department of Pediatrics, University of Toronto, Toronto, ON M5S 1A1, Canada
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Ganji N, Li B, Lee C, Pierro A. Necrotizing enterocolitis: recent advances in treatment with translational potential. Pediatr Surg Int 2023; 39:205. [PMID: 37247104 DOI: 10.1007/s00383-023-05476-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/19/2023] [Indexed: 05/30/2023]
Abstract
Necrotizing enterocolitis (NEC) is one of the most prevalent and devastating gastrointestinal disorders in neonates. Despite advances in neonatal care, the incidence and mortality due to NEC remain high, highlighting the need to devise novel treatments for this disease. There have been a number of recent advancements in therapeutic approaches for the treatment of NEC; these involve remote ischemic conditioning (RIC), stem cell therapy, breast milk components (human milk oligosaccharides, exosomes, lactoferrin), fecal microbiota transplantation, and immunotherapy. This review summarizes the most recent advances in NEC treatment currently underway as well as their applicability and associated challenges and limitations, with the aim to provide new insight into the paradigm of care for NEC worldwide.
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Affiliation(s)
- Niloofar Ganji
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Translational Medicine, Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada
| | - Bo Li
- Translational Medicine, Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada
| | - Carol Lee
- Translational Medicine, Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada
| | - Agostino Pierro
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
- Translational Medicine, Hospital for Sick Children Research Institute, University of Toronto, Toronto, ON, Canada.
- Division of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, 1526-555 University Ave, Toronto, ON, M5G 1X8, Canada.
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Imren C, Vlug LE, de Koning BAE, Diertens T, Snel HE, Suurland J, Swarte RMC, Vermeulen MJ, Keyzer-Dekker CMG. Necrotizing Enterocolitis in a Dutch Cohort of Very Preterm Infants: Prevalence, Mortality, and Long-Term Outcomes. Eur J Pediatr Surg 2022; 32:111-119. [PMID: 35008115 DOI: 10.1055/s-0041-1741544] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION To improve counseling of parents and to guide care strategies, we studied the disease course and outcomes of necrotizing enterocolitis (NEC) up to 2 years of corrected age (CA) from a multidisciplinary perspective. MATERIALS AND METHODS This was a retrospective cohort study in preterm infants (birth weight < 1,500 g, gestational age < 32 weeks), diagnosed with NEC (Bell's stage ≥ II) from 2008 through 2020. Data on prevalence, mortality, surgery, intestinal failure (IF), growth, and neurodevelopment at 2-year follow-up were separately analyzed for medically and surgically treated children. RESULTS Of 3,456 preterm infants, 200 (6%) were diagnosed with NEC, of whom 135 developed an indication for surgery within 7 days after the diagnosis; 28/135 died before surgery, and 37/107 died after an open-and-close procedure. An enterostomy was constructed in 62 patients and an end-to-end anastomosis in 15. The postoperative course was described for 77 patients, of whom 23 developed surgical complications (12/23 incisional hernias, 9/23 anastomotic strictures), 13/77 a short bowel, and 25/77 IF. Sixty-day survival after birth for medical NEC patients was 88% (hazard ratio [HR]: 0.698; p = 0.318), and for surgically treated NEC patients was 40% (HR: 3.729; p < 0.001). At 2-year follow-up, one patient received parenteral nutrition. Severe delay in weight for age, motor, and cognitive development was seen in 3, 6, and 2%, respectively. CONCLUSION In this cohort, the mortality rate was high, especially in surgically treated NEC patients. The surgical complication rate is comparable to previous studies, but in surviving patients, persisting IF and severe delay in growth and neurodevelopment at 2 years CA were relatively rare.
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Affiliation(s)
- Ceren Imren
- Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Lotte E Vlug
- Division of Gastroenterology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Barbara A E de Koning
- Division of Gastroenterology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Tessa Diertens
- Division of Neonatology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Heleen E Snel
- Division of Neonatology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Jill Suurland
- Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Renate M C Swarte
- Division of Neonatology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Marijn J Vermeulen
- Division of Neonatology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
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Syed MK, Al Faqeeh AA, Saeed N, Almas T, Khedro T, Niaz MA, Kanawati MA, Hussain S, Mohammad H, Alshaikh L, Alshaikh L, Abdulhadi A, Alshamlan A, Syed S, Mohamed HKH. Surgical Versus Medical Management of Necrotizing Enterocolitis With and Without Intestinal Perforation: A Retrospective Chart Review. Cureus 2021; 13:e15722. [PMID: 34295576 PMCID: PMC8290905 DOI: 10.7759/cureus.15722] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2021] [Indexed: 11/05/2022] Open
Abstract
Background Necrotizing enterocolitis (NEC) is a debilitating disease that predominantly afflicts premature neonates, although it can also affect term neonates. The clinical features of the ailment vary widely and range from transient feed intolerance to life-threatening complications such as septicemia and disseminated intravascular coagulation. While surgery is usually only reserved for severe cases, such as those presenting with intestinal perforation, the role of surgical management in cases of NEC without perforation remains elusive. Methods A retrospective chart review of patients, three years in duration, was conducted and studied confirmed cases of NEC. The clinical presentations studied included cases of NEC with pneumatosis intestinalis, fixed bowel loop, pneumoperitoneum, and abdominal wall erythema. The patients were divided with regards to their intestinal perforation status and with pertinence to the treatment modality employed (medical or surgical). The results in either group were eventually analyzed in terms of the overall survival rate. Results A total of 48 patients were included in the study, of which 79.16% presented without perforation and 20.83% with perforation. Of the study participants included, 26 were females and 22 were males. Pertinently, no gender predominance was appreciated. In patients without perforation, medical management was noted to boast a lower mortality rate when compared with surgical intervention (15.6% vs 50.0%, respectively). In patients with perforation, the overall mortality was noted to hover at 50.0%, which was higher than that encountered in the non-perforation group. Conclusion In patients with NEC without perforation, surgical treatment confers no comparative therapeutic advantage when compared with medical management alone. Conservative management with broad-spectrum antibiotics including metronidazole yields equally favorable outcomes in such cases.
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Affiliation(s)
| | | | - Noman Saeed
- Neonatology, King Fahad Hospital, Al Baha, SAU
| | - Talal Almas
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Tarek Khedro
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Muhammad Ali Niaz
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - M Ali Kanawati
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Salman Hussain
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Hussain Mohammad
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Lamees Alshaikh
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | - Lina Alshaikh
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
| | | | | | - Saifullah Syed
- Internal Medicine, Royal College of Surgeons in Ireland, Dublin, IRL
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Moschino L, Duci M, Fascetti Leon F, Bonadies L, Priante E, Baraldi E, Verlato G. Optimizing Nutritional Strategies to Prevent Necrotizing Enterocolitis and Growth Failure after Bowel Resection. Nutrients 2021; 13:nu13020340. [PMID: 33498880 PMCID: PMC7910892 DOI: 10.3390/nu13020340] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 02/07/2023] Open
Abstract
Necrotizing enterocolitis (NEC), the first cause of short bowel syndrome (SBS) in the neonate, is a serious neonatal gastrointestinal disease with an incidence of up to 11% in preterm newborns less than 1500 g of birth weight. The rate of severe NEC requiring surgery remains high, and it is estimated between 20–50%. Newborns who develop SBS need prolonged parenteral nutrition (PN), experience nutrient deficiency, failure to thrive and are at risk of neurodevelopmental impairment. Prevention of NEC is therefore mandatory to avoid SBS and its associated morbidities. In this regard, nutritional practices seem to play a key role in early life. Individualized medical and surgical therapies, as well as intestinal rehabilitation programs, are fundamental in the achievement of enteral autonomy in infants with acquired SBS. In this descriptive review, we describe the most recent evidence on nutritional practices to prevent NEC, the available tools to early detect it, the surgical management to limit bowel resection and the best nutrition to sustain growth and intestinal function.
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MESH Headings
- Enterocolitis, Necrotizing/complications
- Enterocolitis, Necrotizing/diagnosis
- Enterocolitis, Necrotizing/prevention & control
- Enterocolitis, Necrotizing/surgery
- Failure to Thrive/prevention & control
- Humans
- Infant
- Infant Nutritional Physiological Phenomena
- Infant, Newborn
- Infant, Premature
- Infant, Premature, Diseases/diagnosis
- Infant, Premature, Diseases/prevention & control
- Infant, Premature, Diseases/surgery
- Intestines/surgery
- Short Bowel Syndrome/etiology
- Short Bowel Syndrome/prevention & control
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Affiliation(s)
- Laura Moschino
- Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (L.M.); (L.B.); (E.P.); (E.B.)
| | - Miriam Duci
- Pediatric Surgery Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (M.D.); (F.F.L.)
| | - Francesco Fascetti Leon
- Pediatric Surgery Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (M.D.); (F.F.L.)
| | - Luca Bonadies
- Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (L.M.); (L.B.); (E.P.); (E.B.)
| | - Elena Priante
- Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (L.M.); (L.B.); (E.P.); (E.B.)
| | - Eugenio Baraldi
- Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (L.M.); (L.B.); (E.P.); (E.B.)
| | - Giovanna Verlato
- Neonatal Intensive Care Unit, Department of Women’s and Children’s Health, University Hospital of Padova, 35128 Padova, Italy; (L.M.); (L.B.); (E.P.); (E.B.)
- Correspondence: ; Tel.: +39-0498211428
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Wertheimer F, Arcinue R, Niklas V. Necrotizing Enterocolitis: Enhancing Awareness for the General Practitioner. Pediatr Rev 2019; 40:517-527. [PMID: 31575803 DOI: 10.1542/pir.2017-0338] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Necrotizing enterocolitis (NEC) has been recognized for well over 5 decades yet remains the most common life-threatening surgical emergency in the newborn. The incidence of NEC has decreased steadily in preterm and very-low-birthweight infants over several decades and is typically uncommon in term newborns and infants with a birthweight greater than 2,500 g. Evidence accumulating during the past decade, however, suggests that practitioners should consider NEC in this broader subset of term infants with chromosomal and congenital anomalies complicated by heart or gastrointestinal defects when signs and symptoms of feeding intolerance, abdominal illness, or sepsis are present. The short- and long-term consequences of NEC are devastating in all infants, and although early disease recognition and treatment are essential, promoting human milk feeding as a primary modality in prevention is critical. This article highlights our current understanding of the pathophysiology, the clinical presentation, the risk factors for NEC in term infants compared with premature infants, and the treatment of NEC and discusses strategies in the prevention of NEC. Finally, we review the long-term consequences of NEC and the importance of primary care practitioners in the long-term care of infants after hospitalization for NEC.
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Affiliation(s)
- Fiona Wertheimer
- Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center, Los Angeles, CA.,Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Roxanne Arcinue
- Keck School of Medicine, University of Southern California, Los Angeles, CA.,Fetal and Neonatal Institute, Division of Neonatology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA
| | - Victoria Niklas
- Prolacta Bioscience Inc, Duarte, CA, and Department of Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA
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Hau EM, Meyer SC, Berger S, Goutaki M, Kordasz M, Kessler U. Gastrointestinal sequelae after surgery for necrotising enterocolitis: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2019; 104:F265-F273. [PMID: 29945925 DOI: 10.1136/archdischild-2017-314435] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 05/26/2018] [Accepted: 05/28/2018] [Indexed: 01/10/2023]
Abstract
OBJECTIVES To document what types of gastrointestinal sequelae were described after surgery for necrotising enterocolitis (NEC) and to analyse their frequency. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline, EMBASE and the Cochrane library (CENTRAL) from 1990 to October 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES We included studies, which provided original data on the occurrence of gastrointestinal sequelae in patients surviving surgery for NEC. Meta-analysis and metaregression to assess heterogeneity were performed for studies including 10 or more patients with gastrointestinal strictures, recurrence of NEC, intestinal failure (IF) and adhesion ileus. RESULTS Altogether 58 studies, including 4260 patients, met the inclusion criteria. Strictures were reported to occur in 24% (95% CI 17% to 31%) of surviving patients, recurrence of NEC in 8% (95% CI 3% to 15%), IF in 13% (95% CI 7% to 19%) and adhesion ileus in 6% (95% CI 4% to 9%). Strictures were more common following enterostomy (30%; 95% CI 23% to 37%) than after primary anastomosis (8%; 95% CI 0% to 23%) and occurred more often after enterostomy without bowel resection than with bowel resection. We found considerable heterogeneity in the weighted average frequency of all sequelae (I2 range: 38%-90%). Intestinal outcomes were poorly defined, there were important differences in study populations and designs, and the reported findings bear a substantial risk of bias. CONCLUSIONS Gastrointestinal sequelae in neonates surviving surgery for NEC are frequent. Long-term follow-up assessing defined gastrointestinal outcomes is warranted.
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Affiliation(s)
- Eva-Maria Hau
- Department of Pediatric Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.,Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Sarah C Meyer
- Department of Pediatric Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Steffen Berger
- Department of Pediatric Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Myrofora Goutaki
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.,Paediatric Respiratory Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Marcin Kordasz
- Department of Pediatric Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Ulf Kessler
- Department of Pediatric Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.,Center of Visceral Surgery, Klinik Beau-Site, Hirslanden, Bern, Switzerland
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10
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Abstract
Necrotizing enterocolitis occurs in 14% of infants less than 1000 g. Preoperative management varies widely, and the only absolute indication for surgery is pneumoperitoneum. Multiple biomarkers and scoring systems are under investigation, but clinical practice is still largely driven by surgeon judgment. Outcomes in panintestinal disease are poor, and multiple creative approaches are used to preserve bowel length. Overall, recovery is complicated in the short and long term. Major sequelae are stricture, short gut syndrome, and neurodevelopmental impairment. Resolving controversies in surgical necrotizing enterocolitis care requires multicenter collaboration for centralized data and tissue repositories, benchmarking, and carrying out prospective randomized controlled trials.
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Affiliation(s)
- Benjamin D Carr
- Section of Pediatric Surgery, Department of Surgery, C.S. Mott Children's Hospital, University of Michigan, 1540 East Hospital Drive, SPC 4211, Ann Arbor, MI 48108, USA
| | - Samir K Gadepalli
- Section of Pediatric Surgery, Department of Surgery, C.S. Mott Children's Hospital, University of Michigan, 1540 East Hospital Drive, SPC 4211, Ann Arbor, MI 48108, USA.
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11
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Knell J, Han SM, Jaksic T, Modi BP. In Brief. Curr Probl Surg 2019. [DOI: 10.1067/j.cpsurg.2018.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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12
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Abstract
Necrotizing enterocolitis (NEC) is a potentially devastating condition that preferentially affects premature and low birth weight infants, with approximately half requiring acute surgical intervention. Surgical consult should be considered early on, and deterioration despite maximal medical therapy or the finding of pneumoperitoneum are the strongest indications for emergent surgical intervention. There is no clear consensus on the optimal surgical approach between peritoneal drainage and laparotomy; the best course of action likely depends on the infant's comorbidities, hemodynamic status, size, disease involvement, and available resources. Patients who develop surgical NEC are at a significant risk for morbidity and mortality, with long-term complications including short bowel syndrome, growth failure, and neurodevelopmental impairment. Further research into strategies that optimize outcomes following surgery for NEC in the neonatal intensive care unit and long-term are paramount.
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13
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Affiliation(s)
- Jamie Knell
- Center for Advanced Intestinal Rehabilitation, Department of Surgery, Boston Children's Hospital, Boston, MA
| | - Sam M Han
- Center for Advanced Intestinal Rehabilitation, Department of Surgery, Boston Children's Hospital, Boston, MA
| | - Tom Jaksic
- Center for Advanced Intestinal Rehabilitation, Department of Surgery, Boston Children's Hospital, Boston, MA; Harvard Medical School, Center for Advanced Intestinal Rehabilitation, Boston Children's Hospital, Boston, MA
| | - Biren P Modi
- Harvard Medical School, Center for Advanced Intestinal Rehabilitation, Boston Children's Hospital, Boston, MA.
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14
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Knell J, Han SM, Jaksic T, Modi BP. WITHDRAWN: In Brief. Curr Probl Surg 2018. [DOI: 10.1067/j.cpsurg.2018.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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15
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Villamil V, Fernández-Ibieta M, Gilabert Ubeda MA, Aranda García MJ, Ruiz Pruneda R, Sánchez Morote JM, Ruiz Jiménez JI. Correlation between pneumoperitoneum and surgical findings and morbidity and mortality in newborns with necrotising enterocolitis. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2018. [DOI: 10.1016/j.anpede.2018.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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16
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Villamil V, Fernández-Ibieta M, Gilabert Ubeda MA, Aranda García MJ, Ruiz Pruneda R, Sánchez Morote JM, Ruiz Jiménez JI. Correlación entre el neumoperitoneo y los hallazgos quirúrgicos y morbimortalidad en recién nacidos con enterocolitis necrosante. An Pediatr (Barc) 2018; 89:205-210. [DOI: 10.1016/j.anpedi.2017.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 11/07/2017] [Accepted: 11/13/2017] [Indexed: 12/13/2022] Open
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17
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Abstract
Necrotizing enterocolitis (NEC) is a frequently encountered condition in the premature neonate, which can have devastating effects. The signs and symptoms of NEC are variable and can be confused with those of sepsis. An abdominal radiograph is often obtained for diagnosis, and findings that indicate NEC include pneumatosis and portal venous gas. The treatment of NEC includes gastrointestinal rest, gastric decompression, broad-spectrum intravenous antibiotics, and systemic support. A finding of pneumoperitoneum signifies intestinal perforation, which requires surgical intervention. Long-term sequelae of NEC include short-gut syndrome, intestinal stricture, and neurodevelopmental delays. The presentation of intestinal stricture can be puzzling. It can appear at presentation as a bowel obstruction or, conversely, as increased stool output or diarrhea. The clinician should have a high level of suspicion for intestinal stricture in a patient with a history of NEC.
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Affiliation(s)
- Barrie S Rich
- Division of Pediatric Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Cohen Children's Medical Center, New Hyde Park, NY
| | - Stephen E Dolgin
- Division of Pediatric Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Cohen Children's Medical Center, New Hyde Park, NY
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18
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Mϋller MJ, Paul T, Seeliger S. Necrotizing enterocolitis in premature infants and newborns. J Neonatal Perinatal Med 2017; 9:233-42. [PMID: 27589549 DOI: 10.3233/npm-16915130] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract (GIT) in premature infants and newborns. It is defined as an ulcerative inflammation of the intestinal wall. The clinical signs of incipient NEC are often very discrete, and range from localized intestinal symptoms to generalized signs of sepsis. NEC is classified depending on its severity into disease states according to the modified Bell's Classification. Treatment of NEC ranges, depending on its severity, from a conservative therapeutic approach to surgery with resection of the affected parts of the intestine. Mortality is considerably high in extremely small preterm infants reaching up to 42% of the affected children. Measures such as breastfeeding or alternatively nutrition with pasteurized human donor milk from a milk bank, administration of probiotics, avoidance of histamine type II receptor antagonists, and restrictive antibiotic treatment should be considered early on for prevention of NEC.
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Affiliation(s)
- M J Mϋller
- Department of Pediatric Cardiology and Intensive Care Medicine, Medical Center Georg August University Göttingen, Germany
| | - T Paul
- Department of Pediatric Cardiology and Intensive Care Medicine, Medical Center Georg August University Göttingen, Germany
| | - S Seeliger
- Department of Pediatric Cardiology and Intensive Care Medicine, Medical Center Georg August University Göttingen, Germany.,St. Elisabeth Children's Hospital, Neuburg/Donau, Germany
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19
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Kargl S, Wagner O, Pumberger W. Ileostomy Complications in Infants less than 1500 grams - Frequent but Manageable. J Neonatal Surg 2017; 6:4. [PMID: 28083490 PMCID: PMC5224761 DOI: 10.21699/jns.v6i1.451] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Accepted: 10/19/2016] [Indexed: 12/15/2022] Open
Abstract
Background: In very low birth weight infants abdominal emergency surgery may result in ileostomy formation. We observed a frequent stoma complications in these patients. This retrospective analysis put light on ileostomy-related problems and complications in very low birth weight (VLBW) infants.
Materials and Methods: In a seven-year retrospective chart review (2008 - 2014) infants with ileostomy formation weighing less than 1500 grams at time of operation were identified and reviewed. Data analysis included demographic data, complications and short term outcomes.
Results: Thirty patients were included. Ileostomy was formed for spontaneous intestinal perforation (SIP) (n=17), meconium obstruction of prematurity (MOP) (n=6), midgut volvulus (MV) (n=5), necrotizing enterocolitis (NEC) (n=1) and Hirschsprung’s disease (HD) (n=1). Three patients died before ileostomy reversal was considered. In seven patients planned ileostomy reversal was done. Twenty infants had stoma related complications (stoma prolapse, prestomal obstruction, stoma retraction, high output stoma, peristomal skin excoriation, and stomal ischemia). Complications did not correlate with underlying diseases. Stomal complications necessitated earlier stoma reversal (mean 62 days). Postoperative complications after stoma reversal occurred in three children (wound dehiscence, adhesion ileus, anastomotic stricture).
Conclusions: Although ileostomy related complications are frequent in very low birth weight infants, mortality is low. Morbidity is manageable.
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Affiliation(s)
- Simon Kargl
- Department of Pediatric Surgery, Kepler University Hospital, Linz
| | - Oliver Wagner
- Department of Neonatology, Kepler University Hospital, Linz
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20
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Abstract
Neonatal surgery is recognized as an independent discipline in general surgery, requiring the expertise of pediatric surgeons to optimize outcomes in infants with surgical conditions. Survival following neonatal surgery has improved dramatically in the past 60 years. Improvements in pediatric surgical outcomes are in part attributable to improved understanding of neonatal physiology, specialized pediatric anesthesia, neonatal critical care including sophisticated cardiopulmonary support, utilization of parenteral nutrition and adjustments in fluid management, refinement of surgical technique, and advances in surgical technology including minimally invasive options. Nevertheless, short and long-term complications following neonatal surgery continue to have profound and sometimes lasting effects on individual patients, families, and society.
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Affiliation(s)
- Mauricio A Escobar
- Pediatric Surgery, Mary Bridge Children׳s Hospital, PO Box 5299, MS: 311-W3-SUR, 311 South, Tacoma, Washington 98415-0299.
| | - Michael G Caty
- Section of Pediatric Surgery, Department of Surgery, Yale-New Haven Children׳s Hospital, New Haven, Connecticut
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21
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Sheng Q, Lv Z, Xu W, Liu J, Wu Y, Shi J, Xi Z. Short-term surgical outcomes of preterm infants with necrotizing enterocolitis: A single-center experience. Medicine (Baltimore) 2016; 95:e4379. [PMID: 27472729 PMCID: PMC5265866 DOI: 10.1097/md.0000000000004379] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The purpose of this study was to analyze the nature of the disease, the surgical procedures, complications, and survival of preterm infants with necrotizing enterocolitis (NEC) at our institution.Medical records of 34 preterm (gestational age <37 weeks) infants with surgical NEC were retrospectively analyzed from January 2010 to December 2014. Patients were divided into 2 groups: low birth weight (LBW, <2500 g, n = 27) and normal birth weight (NBW, ≥2500 g, n = 7).The LBW and NBW groups differed dramatically in gestational age (31.2 ± 2.2 vs. 36.3 ± 0.5 weeks), and respiratory support (55.5% vs. 0%). The median age of NEC onset was 12 and 5 postnatal days respectively. There was an inverse association between gestational age and day of NEC onset (r = -0.470). Pneumoperitoneum, positive paracentesis, and progressive clinical deterioration were the indications for laparotomy. There was no difference in the extent of disease, in the bowel involvement, in the surgical procedures, and in the postoperative complication rates between the 2 groups. The choice of procedure has often depended upon the extent of disease (enterostomy was performed in most localized and multifocal infants, simple drainage was used in 83.3% pan-intestinal patients, P < 0.001). Postoperative complications occurred in 70.5% patients. The most common complications were sepsis, intestinal stricture, and short bowel syndrome. The median hospital stay was significantly longer in the LBW group (65 vs. 19 days, P = 0.004). The overall postoperative 180-day survival rate was 70.6% (70.4% vs. 71.5%, P = 0.890, log rank test). The severity of illness was the main risk factor for mortality (8.3% in localized, 18.7% in multifocal, and 100% in pan-intestinal, P < 0.001).The short-term outcomes for surgical NEC are grave. The high mortality and postoperative complications in this study mandate urgent improvements in early recognition, expeditious operation, and better perioperative care.
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Affiliation(s)
| | - Zhibao Lv
- Department of General Surgery
- Correspondence: Zhibao Lv, Department of General Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University. No. 355, Luding Rd, Shanghai 200062, P.R. China (e-mail: ; )
| | | | | | - Yibo Wu
- Department of General Surgery
| | | | - Zhengjun Xi
- Department of Pathology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China
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22
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23
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He Y, Zhong Y, Yu J, Cheng C, Wang Z, Li L. Ultrasonography and radiography findings predicted the need for surgery in patients with necrotising enterocolitis without pneumoperitoneum. Acta Paediatr 2016; 105:e151-5. [PMID: 26676409 DOI: 10.1111/apa.13315] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 11/02/2015] [Accepted: 12/11/2015] [Indexed: 11/28/2022]
Abstract
AIM The timing of surgical intervention in patients with necrotising enterocolitis (NEC) without pneumoperitoneum remains unclear. This study aimed to identify the predictors associated with surgical intervention in such patients and to assess how effective imaging reports were as an aid to surgical decision-making. METHODS We collected clinical data, laboratory investigations and imaging findings on NEC patients without pneumoperitoneum. A critical imaging report was defined as persistent dilation of bowel loops and evidence of portal venous gas on radiography and thickening of the bowel wall, absent peristalsis and evidence of echogenic-free fluid on sonography. Independent predictors of surgical NEC were identified using multivariate logistic regression analysis. Sensitivity and specificity analyses were performed for the imaging findings, and receiver operator characteristic curve analysis was used to evaluate the predictive accuracy. RESULTS Of the 238 neonates studied, 54 (22.69%) required surgical intervention. The multivariate logistic regression analysis showed that abdominal erythema, C-reactive protein levels and the critical imaging report were independent predictors of the need for surgical intervention. The critical imaging report was the most powerful predictor of surgical NEC. CONCLUSION Both ultrasonography and radiography findings proved helpful in predicting the need for surgery in NEC without pneumoperitoneum.
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Affiliation(s)
- Yu He
- Department of Neonatology; Children's Hospital; Chongqing Medical University; Chongqing China
- Chongqing Key Laboratory of Paediatrics; Chongqing China
- Ministry of Education Key Laboratory of Child Development and Disorder; Children's Hospital; Chongqing Medical University; Chongqing China
- China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing China
| | - Ying Zhong
- Department of Neonatology; The Children's Hospital Zhejiang University School of Medicine; Chongqing China
| | - Jialin Yu
- Department of Neonatology; Children's Hospital; Chongqing Medical University; Chongqing China
- Chongqing Key Laboratory of Paediatrics; Chongqing China
- Ministry of Education Key Laboratory of Child Development and Disorder; Children's Hospital; Chongqing Medical University; Chongqing China
- China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing China
| | - Chen Cheng
- Department of Neonatology; Children's Hospital; Chongqing Medical University; Chongqing China
- Chongqing Key Laboratory of Paediatrics; Chongqing China
- Ministry of Education Key Laboratory of Child Development and Disorder; Children's Hospital; Chongqing Medical University; Chongqing China
- China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing China
| | - Zhengli Wang
- Department of Neonatology; Children's Hospital; Chongqing Medical University; Chongqing China
- Chongqing Key Laboratory of Paediatrics; Chongqing China
- Ministry of Education Key Laboratory of Child Development and Disorder; Children's Hospital; Chongqing Medical University; Chongqing China
- China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing China
| | - Luquan Li
- Department of Neonatology; Children's Hospital; Chongqing Medical University; Chongqing China
- Chongqing Key Laboratory of Paediatrics; Chongqing China
- Ministry of Education Key Laboratory of Child Development and Disorder; Children's Hospital; Chongqing Medical University; Chongqing China
- China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing China
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24
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Application of Mitomycin C after dilation of an anastomotic stricture in a newborn with necrotizing enterocolitis. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2016. [DOI: 10.1016/j.epsc.2015.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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25
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Tan YW, Merchant J, Sharma V, Davies B, Singh S, Stewart R, More B. Extensive Necrotising Enterocolitis: Objective Evaluation of the Role of Second-Look Laparotomy in Bowel Salvage and Survival. World J Surg 2015; 39:3016-22. [DOI: 10.1007/s00268-015-3203-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Maezawa S, Fujita M, Sato T, Kushimoto S. Delayed intestinal stricture following non-resectional treatment for non-occlusive mesenteric ischemia associated with hepatic portal venous gas: a case report. BMC Surg 2015; 15:37. [PMID: 25885337 PMCID: PMC4392740 DOI: 10.1186/s12893-015-0028-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 03/24/2015] [Indexed: 12/19/2022] Open
Abstract
Background Hepatic portal venous gas associated with non-occlusive mesenteric ischemia is indicative of a serious pathology that leads to bowel necrosis and it has a high mortality rate. Although non-occlusive mesenteric ischemia is acknowledged as a condition that requires early surgical treatment, it has been reported that bowel necrosis and surgical resection of the gangrenous lesion may be avoided if the condition is identified quickly and the cause is detected at an early phase. However, no reports or guidelines have been published that describe the management of patients in whom bowel necrosis and surgical treatment were avoided. We report the case of a patient who presented with non-occlusive mesenteric ischemia who was managed with non-resectional treatment at an early phase and had a delayed small-bowel stricture. Case presentation A 24-year-old man presented to the hospital with fever, abdominal pain, and vomiting. Abdominal computed tomography confirmed a diffuse gaseous distention with small-bowel pneumatosis and hepatic portal venous gas. An urgent laparotomy was performed, because septic shock associated with diffuse peritonitis and bowel necrosis was strongly suspected. Although we found purulent ascites and a perforated appendix at the time of surgery, gangrenous and transmural ischemic changes were not evident in the small bowel and colon. We performed an appendectomy without a bowel resection, and the patient was discharged on an oral diet. However, he was re-admitted to hospital, because 4 days after discharge he developed postoperative paralytic ileus. Non-operative management was chosen, but his symptoms did not improve. We decided to perform a laparotomy 40 days after the initial operation, and a considerable adhesion was detected. Therefore, only a synechotomy was performed. On day 57, he experienced symptoms that were associated with bowel obstruction once again. On day 59, a partial resection of the jejunum was performed. Severe luminal strictures were apparent within the jejunum, and marked structural changes were evident. Conclusion While non-surgical management can be chosen for selected patients with non-occlusive mesenteric ischemia, continuous observation to evaluate the development of delayed strictures that lead to bowel obstructions is required in patients who undergo non-resectional treatment.
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Affiliation(s)
- Shota Maezawa
- Department of Emergency and Critical Care Medicine/Emergency Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Motoo Fujita
- Department of Emergency and Critical Care Medicine/Emergency Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Takeaki Sato
- Department of Emergency and Critical Care Medicine/Emergency Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Shigeki Kushimoto
- Department of Emergency and Critical Care Medicine/Emergency Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. .,Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
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27
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Kandasamy J, Huda S, Ambalavanan N, Jilling T. Inflammatory signals that regulate intestinal epithelial renewal, differentiation, migration and cell death: Implications for necrotizing enterocolitis. ACTA ACUST UNITED AC 2014; 21:67-80. [PMID: 24533974 DOI: 10.1016/j.pathophys.2014.01.001] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Necrotizing enterocolitis is a disease entity with multiple proposed pathways of pathogenesis. Various combinations of these risk factors, perhaps based on genetic predisposition, possibly lead to the mucosal and epithelial injury that is the hallmark of NEC. Intestinal epithelial integrity is controlled by a tightly regulated balance between proliferation and differentiation of epithelium from intestinal epithelial stem cells and cellular loss by apoptosis. various signaling pathways play a key role in creating and maintaining this balance. The aim of this review article is to outline intestinal epithelial barrier development and structure and the impact of these inflammatory signaling and regulatory pathways as they pertain to the pathogenesis of NEC.
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Affiliation(s)
- Jegen Kandasamy
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Alabama at Birmingham, USA
| | - Shehzad Huda
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Alabama at Birmingham, USA
| | - Namasivayam Ambalavanan
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Alabama at Birmingham, USA
| | - Tamas Jilling
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Alabama at Birmingham, USA.
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Abstract
Necrotizing enterocolitis (NEC) is the most common surgical emergency occurring in neonatal intensive care unit (NICU) patients. Among patients with NEC, those that require surgery experience the poorest outcomes and highest mortality. Surgical intervention, while attempting to address the intestinal injury and ongoing mulitfactorial physiologic insults in NEC is associated with its own stresses that may compound the ongoing physiologic derangement. Surgery is thus reserved for those patients with clear indication for intervention such as pneumoperitoneum, confirmed stool or pus in the peritoneal cavity, or worsening clinical status. The purpose of this review is to briefly describe the physiologic stress induced by surgical intervention in the preterm, low birth weight patient with NEC and to provide a contemporary overview of available surgical management options for NEC. The optimal surgical plan employed is strongly influenced by clinical judgment and theoretical benefits in terms of minimizing physiologic stressors while providing temporary and/or definitive treatment in a timely fashion. While the choice of operation has not been shown to have a significant effect on any clinically important outcomes, ongoing investigations continue to study both short and long-term outcomes in patients with NEC.
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Affiliation(s)
- Mehul V Raval
- Division of Pediatric Surgery, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA
| | - R Lawrence Moss
- Division of Pediatric Surgery, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
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29
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Gaudin A, Farnoux C, Bonnard A, Alison M, Maury L, Biran V, Baud O. Necrotizing enterocolitis (NEC) and the risk of intestinal stricture: the value of C-reactive protein. PLoS One 2013; 8:e76858. [PMID: 24146936 PMCID: PMC3795640 DOI: 10.1371/journal.pone.0076858] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 09/04/2013] [Indexed: 11/18/2022] Open
Abstract
Necrotizing enterocolitis (NEC) is a severe complication frequently seen during the neonatal period associated with high mortality rate and severe and prolonged morbidity including Post-NEC intestinal stricture. The aim of this study is to define the incidence and risk factors of these post-NEC strictures, in order to better orient their medicosurgical care. Sixty cases of NEC were retrospectively reviewed from a single tertiary center with identical treatment protocols throughout the period under study, including systematic X-ray contrast study. This study reports a high rate of post-NEC intestinal stricture (n = 27/48; 57% of survivors), either in cases treated surgically (91%) and after the medical treatment of NEC (47%). A colonic localization of the strictures was more frequent in medically-treated patients than in those with NEC treated surgically (87% vs. 50%). The length of the strictures was significantly shorter in case of NEC treated medically. No deaths were attributable to the presence of post-NEC stricture. The mean hospitalization time in NICU and the median age at discontinuation of parenteral nutrition were longer in the group with stricture, but this difference was not significant. The median age at discharge was significantly higher in the group with stricture (p = 0.02). The occurrence of post-NEC stricture was significantly associated with the presence of parietal signs of inflammation and thrombopenia (<100 000 platelets/mm3). The mean maximum CRP concentration during acute phase was significantly higher in infants who developed stricture (p<0.001), as was the mean duration of the elevation of CRP levels (p<0.001). The negative predictive value of CRP levels continually <10 mg/dL for the appearance of stricture was 100% in our study. In conclusion, this retrospective and monocentric study demonstrates the correlation between the intensity of the inflammatory syndrome and the risk of secondary intestinal stricture, when systematic contrast study is performed following NEC.
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Affiliation(s)
- Aurélie Gaudin
- Neonatal Intensive Care Unit, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
| | - Caroline Farnoux
- Neonatal Intensive Care Unit, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
| | - Arnaud Bonnard
- Department of General Pediatric Surgery, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
| | - Marianne Alison
- Department of Pediatric Radiology, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
| | - Laure Maury
- Neonatal Intensive Care Unit, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
| | - Valérie Biran
- Neonatal Intensive Care Unit, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
| | - Olivier Baud
- Neonatal Intensive Care Unit, Robert Debré Children University Hospital and Denis Diderot Paris University, APHP, Paris, France
- * E-mail:
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Linder N, Hammel N, Hernandez A, Fridman E, Dlugy E, Herscovici T, Klinger G. Intestinal perforation in very-low-birth-weight infants with necrotizing enterocolitis. J Pediatr Surg 2013; 48:562-567. [PMID: 23480913 DOI: 10.1016/j.jpedsurg.2012.08.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2012] [Revised: 08/19/2012] [Accepted: 08/20/2012] [Indexed: 02/01/2023]
Abstract
PURPOSE To identify risk factors for intestinal perforation in very-low-birth-weight (VLBW) infants with necrotizing enterocolitis (NEC). METHODS Retrospective case-control study over a 10-year period, using univariate and multivariate logistic regression analyses to compare all VLBW infants treated for perforated NEC, with two age and weight-matched groups: infants with non-perforated NEC and infants without NEC. RESULTS Twenty infants with perforated NEC were matched to 20 infants with non-perforated NEC and 38 infants without NEC. Infants with perforated NEC were younger (p<0.01) and had higher rates of abdominal distention, metabolic acidosis, hyperglycemia and elevated liver enzymes (p<0.05). On logistic regression analysis, abdominal distention was associated with an increased risk of intestinal perforation (OR 39.8, 95% CI 2.71-585) and late onset of NEC (one-day increments) was associated with a decreased risk (OR 0.93, 95% CI 0.87-1.0). CONCLUSION Identification of abdominal distention at an early age in VLBW infants should lead to increased vigilance for signs of perforated NEC and may enable early intervention.
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Affiliation(s)
- Nehama Linder
- Neonatal Intensive Care Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
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Abstract
Necrotizing enterocolitis (NEC), a common cause of neonatal morbidity and mortality, is strongly associated with prematurity and typically occurs following initiation of enteral feeds. Mild NEC is adequately treated by cessation of enteral feeding, empiric antibiotics, and supportive care. Approximately 50% of affected infants will develop progressive intestinal necrosis requiring urgent operation. Several surgical techniques have been described, but there is no clear survival benefit for any single operative approach. While debate continues regarding the optimal surgical management for infants with severe NEC, future progress will likely depend on the development of improved diagnostic tools and preventive therapies.
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Abstract
Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease of premature newborns, thought to result in part from overactivity of the innate immune system. NEC has been well-studied from the perspective of prevention; however, after the disease onset, there are limited treatment options to control its progression. This review discusses four potential therapies that target the overactive immune response in NEC: pentoxifylline, platelet activating factor modulators, glucocorticoids, and vasoactive substances. In addition, given the similar pathogenesis of NEC and inflammatory bowel disease (IBD), we propose that IBD therapies could provide promising leads for novel strategies with which to treat NEC.
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Affiliation(s)
- Sanjiv Harpavat
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, USA.
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Abdelmaaboud M, Mohammed A. Early Versus Late Minimal Enteral Feeding in Weeks Preterm Growth-Restricted neonates with Abnormal Antenatal Doppler Studies. J Matern Fetal Neonatal Med 2012:1-20. [PMID: 23211122 DOI: 10.3109/14767058.2012.695821] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Abstract Background: Preterm and growth-restricted babies are at high risk of milk intolerance and necrotising enterocolitis, as well as post-natal growth failure. Objective: To evaluate the effects of an "early" enteral feeding regimen, starting on day 2 after birth compared to late enteral feeding, starting on day 6 after birth in preterm growth restricted babies with abnormal antenatal Doppler studies regarding the incidence of NEC and feeding intolerance. Patients and Methods: Babies with gestational age below 37 weeks, and with birth weight below 10th centile for gestational age, will be randomly allocated to an "early" or "late" enteral feeding regimen. Results: Hundred-thirty three infants enrolled in the study: 66 received early feeding and 67 received delayed feeding. The incidence of NEC and feeding intolerance was not significantly different between the two groups. Conclusion: Early minimal enteral feeding (MEF) of preterm infants with IUGR and abnormal antenatal Doppler results may not have a significant effect on the incidence of NEC or feeding intolerance.
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Dalton BGA, Walters KC, Dassinger MS. Case report: delayed perforation after definitive treatment of focal intestinal perforation with a peritoneal drain. Case Rep Surg 2012; 2012:316147. [PMID: 22966475 PMCID: PMC3433118 DOI: 10.1155/2012/316147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 07/17/2012] [Indexed: 11/18/2022] Open
Abstract
Focal intestinal perforation (FIP) has long been described in the pediatric literature. Peritoneal drainage (PD) is widely used as treatment for focal intestinal perforation. Here we report a premature infant that underwent PD on day of life 9 for a FIP. The infant recovered well from this episode and was discharged home without known sequelae. Subsequently, the same patient presented 16 months later with peritonitis. A perforation was discovered at laparotomy without evidence of surrounding necrosis. Given this finding, we believe this second episode of perforation was at the same site as the initial episode of FIP. The finding of FIP has been described without findings of surrounding necrosis. However, we believe this to be the first report of delayed perforation greater than 1 year from initial presentation after FIP treated definitively with peritoneal drain.
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Affiliation(s)
- Brian G. A. Dalton
- Spartanburg Regional Medical Center, 101 E. Wood St. Spartanburg, SC 29302, USA
| | - Kenneth C. Walters
- Arkansas Children's Hospital, One Children's Way, Little Rock, AR 72202, USA
| | - Melvin S. Dassinger
- Arkansas Children's Hospital, One Children's Way, Little Rock, AR 72202, USA
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Wu SF, Caplan M, Lin HC. Necrotizing enterocolitis: old problem with new hope. Pediatr Neonatol 2012; 53:158-63. [PMID: 22770103 DOI: 10.1016/j.pedneo.2012.04.001] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Revised: 09/23/2011] [Accepted: 04/26/2012] [Indexed: 12/11/2022] Open
Abstract
The incidence of necrotizing enterocolitis (NEC) and mortality rate associated with this disease are not decreasing despite more than three decades of intensive research investigation and advances in neonatal intensive care. Although the etiology of NEC is not clearly elucidated, the most accepted hypothesis at present is that enteral feeding in the presence of intestinal hypoxia-ischemia-reperfusion, and colonization with pathogens provokes an inappropriately accentuated inflammatory response by the immature intestinal epithelial cells of the preterm neonate. However, delayed colonization of commensal flora with dysbiotic flora with a predominance of pathologic microorganisms plays a fundamental role in the pathogenesis of NEC. Recent studies have further identified that NEC infants have less diverse flora compared to age-matched controls without NEC. Increased gastric residual volume may be an early sign of NEC. An absolute neutrophil count of <1.5 × 10(9)/L and platelets below 100 × 10(9)/L are associated with an increased risk for mortality and gastrointestinal morbidity. Nonspecific supportive medical management should be initiated promptly. Sudden changes in vital signs such as tachycardia or impending shock may indicate perforation. A recent meta-analysis investigating using probiotics for prevention of NEC with a total of 2176 preterm very low birth weight infants found a success rate of just 1/25. Careful monitoring of the residual volume, and of serious changes in hemograms and vital signs may help in early diagnosis and prediction of when to perform medical or early surgical intervention. In term of prevention, administration of oral probiotics containing Bifidobacterium and Lactobacillus is a simple and safe method that attempts to early establish of commensal flora balance to inhibit pathogenic flora and an inflammatory response.
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Affiliation(s)
- Shu-Fen Wu
- Department of Pediatrics, China Medical University Hospital, China Medical University, Taichung, Taiwan
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Abstract
Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal disease of premature neonates and is a serious cause of morbidity and mortality. NEC is one of the leading causes of death in neonatal intensive care units. Surgical treatment is necessary in patients whose disease progresses despite medical therapy. Surgical options include peritoneal drainage and laparotomy, with studies showing no difference in outcome related to approach. Survivors, particularly those requiring surgery, face serious sequelae.
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Giannone PJ, Alcamo AA, Schanbacher BL, Nankervis CA, Besner GE, Bauer JA. Poly(ADP-ribose) polymerase-1: a novel therapeutic target in necrotizing enterocolitis. Pediatr Res 2011; 70:67-71. [PMID: 21399558 PMCID: PMC3111902 DOI: 10.1203/pdr.0b013e31821928ff] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of infancy, afflicting 11% of infants born 22-28 wk GA. Both inflammation and oxidation may be involved in NEC pathogenesis through reactive nitrogen species production, protein oxidation, and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme activated to facilitate DNA repair using nicotinamide adenine dinucleotide (NAD+) as a substrate. However, in the presence of severe oxidative stress and DNA damage, PARP-1 overactivation may ensue, depleting cells of NAD+ and ATP, killing them by metabolic catastrophe. Here, we tested the hypothesis that NO dysregulation in intestinal epithelial cells during NEC leads to marked PARP-1 expression and that administration of a PARP-1 inhibitor (nicotinamide) attenuates intestinal injury in a newborn rat model of NEC. In this model, 56% of control pups developed NEC (any stage) versus 14% of pups receiving nicotinamide. Forty-four percent of control pups developed high-grade NEC (grades 3-4), whereas only 7% of pups receiving nicotinamide developed high-grade NEC. Nicotinamide treatment protects pups against intestinal injury incurred in the newborn rat NEC model. We speculate that PARP-1 overactivation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC.
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Affiliation(s)
- Peter J Giannone
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
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Abstract
Necrotizing enterocolitis (NEC) is a leading cause of death among patients in the neonatal intensive care unit, carrying a mortality rate of 15-30%. Its pathogenesis is multifactorial and involves an overreactive response of the immune system to an insult. This leads to increased intestinal permeability, bacterial translocation, and sepsis. There are many inflammatory mediators involved in this process, but thus far none has been shown to be a suitable target for preventive or therapeutic measures. NEC usually occurs in the second week of life after the initiation of enteral feeds, and the diagnosis is made based on physical examination findings, laboratory studies, and abdominal radiographs. Neonates with NEC are followed with serial abdominal examinations and radiographs, and may require surgery or primary peritoneal drainage for perforation or necrosis. Many survivors are plagued with long term complications including short bowel syndrome, abnormal growth, and neurodevelopmental delay. Several evidence-based strategies exist that may decrease the incidence of NEC including promotion of human breast milk feeding, careful feeding advancement, and prophylactic probiotic administration in at-risk patients. Prevention is likely to have the greatest impact on decreasing mortality and morbidity related to NEC, as little progress has been made with regard to improving outcomes for neonates once the disease process is underway.
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Affiliation(s)
- Loren Berman
- Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA
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Bucher BT, McDuffie LA, Shaikh N, Tarr PI, Warner BB, Hamvas A, White FV, Erwin CR, Warner BW. Bacterial DNA content in the intestinal wall from infants with necrotizing enterocolitis. J Pediatr Surg 2011; 46:1029-33. [PMID: 21683193 PMCID: PMC3118995 DOI: 10.1016/j.jpedsurg.2011.03.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2011] [Accepted: 03/26/2011] [Indexed: 11/17/2022]
Abstract
PURPOSE The objective of our study was to quantify mucosal bacterial DNA within specimens from neonates undergoing small bowel resection for necrotizing enterocolitis (NEC). METHODS We obtained clinical information and pathologic specimens from all infants diagnosed with NEC who underwent surgical treatment at our institution from 1999 to 2008. Bacterial and human DNA were isolated from paraffin-embedded surgical specimens, and real time polymerase chain reaction was used to amplify bacterial and human genes. Linear regression was used to quantify the amount of human and bacterial DNA in our specimens. RESULTS From a cohort of 50 infants, we identified 23 infants who underwent both surgical resection and subsequent intestinal reanastomosis. Thirteen (59%) of the neonates had Bell stage III NEC, and 9 (41%) had stage II. There was significantly more bacterial DNA in the resection specimens than in the reanastomosis specimens. This corresponds to a median (interquartile range) increase of 1.81 (1.11-4.69)-fold bacterial DNA in the resection specimen compared with the reanastomosis specimen (P < .05). CONCLUSION There is more bacterial DNA in infants with acute NEC compared with the same infants after the NEC had clinically resolved. These findings underscore the potential relevance of adherent or invasive bacteria across the bowel wall in the pathogenesis of NEC.
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Affiliation(s)
- Brian T. Bucher
- Division of Pediatric Surgery, Department of Surgery Washington University School of Medicine, St. Louis, MO
| | - Lucas A. McDuffie
- Division of Pediatric Surgery, Department of Surgery Washington University School of Medicine, St. Louis, MO
| | - Nurmohammad Shaikh
- Divison of Gastroenterology Washington University School of Medicine, St. Louis, MO
| | - Phillip I. Tarr
- Divison of Gastroenterology Washington University School of Medicine, St. Louis, MO
| | - Barbara B. Warner
- Newborn Medicine, Department of Pediatrics Washington University School of Medicine, St. Louis, MO
| | - Aaron Hamvas
- Newborn Medicine, Department of Pediatrics Washington University School of Medicine, St. Louis, MO
| | - Francis V. White
- Department of Pathology and Immunology; Washington University School of Medicine, St. Louis, MO
| | - Christopher R. Erwin
- Division of Pediatric Surgery, Department of Surgery Washington University School of Medicine, St. Louis, MO
| | - Brad W. Warner
- Division of Pediatric Surgery, Department of Surgery Washington University School of Medicine, St. Louis, MO
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Abstract
Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and death. The pathophysiology is poorly understood. Prevailing evidence suggests that NEC is due to an inappropriate inflammatory response of the immature gut to some undefined insult. The mortality rate (15%-25%) for affected infants has not changed appreciably in 30 years. Many infants with NEC recover uneventfully with medical therapy and have long-term outcomes similar to unaffected infants of matched gestational age. Infants with progressive disease requiring surgical intervention suffer almost all of the mortality and morbidity. Of these, approximately 30%-40% will die of their disease and most of the remainder will develop long-term neurodevelopmental and gastrointestinal morbidity. Recent randomized trials suggest that the choice of operation does not influence patient outcome. Current work is focusing on developing a better understanding of the pathogenesis and improving means to identify which infants are at greatest risk of disease progression.
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Affiliation(s)
- Marion C W Henry
- Section of Pediatric Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA
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de Souza JCK, Fraga JC. Is mortality rate influenced by the site of involvement in neonates undergoing laparotomy for necrotizing enterocolitis? J Pediatr Surg 2009; 44:1534-9. [PMID: 19635301 DOI: 10.1016/j.jpedsurg.2008.12.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2008] [Revised: 12/13/2008] [Accepted: 12/17/2008] [Indexed: 11/19/2022]
Abstract
PURPOSE The aim of the study was to evaluate the effect of disease site on the mortality rate of newborns with necrotizing enterocolitis (NEC) undergoing exploratory laparotomy. METHODS The study used prospective cohort of 141 consecutive newborns with NEC who underwent laparotomy from November 1991 to December 2005. RESULTS One hundred nineteen (84.4%) newborns were premature. Small for gestational age was observed in 57 (40.4%). Sixty-eight (48.2%) infants died. Bivariate analysis revealed that involvement of the jejunum and ileum was associated with high mortality rates (20 deaths; 76.9%; odds ratio [OR], 20; 95% confidence interval [CI], 4.6-96.3; P < .001) and that coinvolvement of the jejunum was associated with greater disease extent. After controlling for individual variables, logistic regression showed that the mortality associated with jejunum and ileum involvement (OR, 0.61; 95% CI, 0.06-6.14; P = .68) did not differ from that associated with large bowel involvement (OR, 2.91; 95% CI, 0.81-10.50; P = .10). When the jejunum was involved with the disease, the percentage of involvement of the entire intestine was 72%, and the mortality rate was 85.1%. When the other bowel segments were involved, the global percentage of disease extent ranged from 42% to 49%, and the mortality rate from 51.9% to 71.8%. After multivariable adjustment disease site, jejunal involvement appeared to be only a surrogate marker of disease extent. CONCLUSIONS The NEC-related mortality in newborns undergoing laparotomy was not influenced by disease site (small or large bowel). However, jejunum coinvolvement was a marker of greater disease extent and therefore of poor prognosis.
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Stomal complications in the newborn with necrotizing enterocolitis. J Surg Res 2009; 157:275-8. [PMID: 19815238 DOI: 10.1016/j.jss.2009.06.005] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2009] [Revised: 05/21/2009] [Accepted: 06/08/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND Infants who develop necrotizing enterocolitis (NEC) are usually managed with fecal diversion. The integrity of the bowel being diverted is often suboptimal. Our clinical impression is that stomas created in this circumstance are fraught with complications. The purpose of this study is to quantify the rate of these complications and identify risk factors. METHODS A retrospective data collection from May 1999 to May 2008 on infants undergoing laparotomy for NEC was conducted. Data collected included gestational age, birth weight, age, and weight at operation, indications for surgical therapy, procedure performed, time to stoma output, time to takedown of stoma, complication directly related to the ostomy, and mortality. Data comparisons were analyzed statistically using chi(2), Pearson's correlation, Fisher's exact test, or a 2-tailed Student's t-test with significance reported for P<0.05. RESULTS A total of 73 patients were identified. Mean gestational age was 28 (+/-4) wk, mean birth weight was 1247 (+/-713) g. Mean age at the time of surgery was 23 (+/-27) d, and mean weight at operation was 1513 (+/-1306) g. The most common indication for surgical intervention was pneumoperitoneum (n=43, 58%). The most common level of intestinal diversion was the ileum (n=63, 85%). In-house mortality was 13%. There were 31 patients (42%) who developed 32 stoma-related complications. Demographic or preoperative variables that were a significant predictor of stoma-related complications were gestational age (P=0.003) and preoperative weight (P=0.024). CONCLUSION Premature infants carry a risk for developing stoma-related complications. Within that cohort, there is significantly increased risk of stoma-related complications in patients who are younger in gestational age and who have low preoperative weight. Future prospective studies may allow insight into preventative practices.
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Ron O, Davenport M, Patel S, Kiely E, Pierro A, Hall NJ, Ade-Ajayi N. Outcomes of the "clip and drop" technique for multifocal necrotizing enterocolitis. J Pediatr Surg 2009; 44:749-54. [PMID: 19361635 DOI: 10.1016/j.jpedsurg.2008.09.031] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2008] [Revised: 09/16/2008] [Accepted: 09/30/2008] [Indexed: 12/01/2022]
Abstract
BACKGROUND The "clip and drop" (CD) has been proposed as a useful strategy in the management of severe multifocal necrotizing enterocolitis (NEC). There is little published data on clinical outcomes after this intervention. We report a 2-center experience with this technique. METHODS A retrospective review of infants who underwent CD between 1998 and 2006 at 2 tertiary pediatric surgery centers. Data recorded included intestinal resections, interval between laparotomies, anastomoses at subsequent surgery, time to full feeds, and complications including mortality. Data are reported as median with ranges. RESULTS Thirteen infants (7 male, 6 female) with a birth weight of 811 (514-2110) g underwent CD of up to 5 bowel segments. In 8 of 9 early survivors, all CD segments were viable. Six patients (46%) were alive at 29 (9-96) months. Survivors underwent 4 (3-4) laparotomies and 4 (2-6) bowel anastomoses and had intestinal continuity restored at 67 (51-162) days. CONCLUSIONS With multiple interventions, half the infants in this high-risk group survived and achieved full enteral feeds. The CD is a valuable technique in a selected group of infants with fulminant NEC.
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Affiliation(s)
- Ori Ron
- Department of Pediatric Surgery, King's College Hospital NHS Trust, SE5 9RS London, United Kingdom
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46
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Oh BY, Choi KJ. Prognostic Factors of Surgically Treated Pneumoperitoneum in Neonates. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2009. [DOI: 10.4174/jkss.2009.77.2.127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Bo-young Oh
- Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea
| | - Kum-ja Choi
- Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea
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Guner YS, Chokshi N, Petrosyan M, Upperman JS, Ford HR, Grikscheit TC. Necrotizing enterocolitis--bench to bedside: novel and emerging strategies. Semin Pediatr Surg 2008; 17:255-65. [PMID: 19019294 DOI: 10.1053/j.sempedsurg.2008.07.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Necrotizing enterocolitis (NEC) is a devastating illness that predominantly affects premature neonates. The mortality associated with this disease has changed very little during the last two decades. Neonates with NEC fall into two categories: those who respond to medical management alone and those who require surgical treatment. The disease distribution may be focal, multifocal, or panintestinal. Surgical treatment should therefore be based on disease presentation. Recent studies have added significant insight into our understanding of the pathogenesis of NEC. Several groups have shown that upregulation of nitric oxide plays an integral role in the development of epithelial injury in NEC. As a result, some treatment strategies have been aimed at abrogating the toxic effects of nitric oxide. In addition, several investigators have reported the cytoprotective effect of epidermal growth factor, which is found in high levels in breast milk, on the intestinal epithelium. Thus, fortification of infant formula with specific growth factors could soon become a preferred strategy to accelerate intestinal maturation in the premature neonate to prevent the development of NEC. One of the most devastating complications of NEC is the development of short bowel syndrome (SBS). The current treatment of SBS involves intestinal lengthening procedures or bowel transplantation. A novel emerging method for treating SBS involves the use of tissue-engineered intestine. In laboratory animals, tissue-engineered small intestine has been shown to be successful in treating intestinal failure. This article examines recent data regarding surgical treatment options for NEC as well as emerging treatment modalities.
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Affiliation(s)
- Yigit S Guner
- Department of Surgery, Childrens Hospital Los Angeles, and the Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA
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Markel TA, Crisostomo PR, Lahm T, Novotny NM, Rescorla FJ, Tector AJ, Meldrum DR. Stem cells as a potential future treatment of pediatric intestinal disorders. J Pediatr Surg 2008; 43:1953-63. [PMID: 18970924 PMCID: PMC2584666 DOI: 10.1016/j.jpedsurg.2008.06.019] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2008] [Revised: 05/18/2008] [Accepted: 06/22/2008] [Indexed: 12/27/2022]
Abstract
All surgical disciplines encounter planned and unplanned ischemic events that may ultimately lead to cellular dysfunction and death. Stem cell therapy has shown promise for the treatment of a variety of ischemic and inflammatory disorders where tissue damage has occurred. As stem cells have proven beneficial in many disease processes, important opportunities in the future treatment of gastrointestinal disorders may exist. Therefore, this article will serve to review the different types of stem cells that may be applicable to the treatment of gastrointestinal disorders, review the mechanisms suggesting that stem cells may work for these conditions, discuss current practices for harvesting and purifying stem cells, and provide a concise summary of a few of the pediatric intestinal disorders that could be treated with cellular therapy.
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Affiliation(s)
- Troy A. Markel
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Paul R. Crisostomo
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Tim Lahm
- Department of Pulmonary and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Nathan M. Novotny
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | | | - A. Joseph Tector
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Daniel R. Meldrum
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
- Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana
- Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana
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Evidence vs experience in the surgical management of necrotizing enterocolitis and focal intestinal perforation. J Perinatol 2008; 28 Suppl 1:S14-7. [PMID: 18446170 DOI: 10.1038/jp.2008.44] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are neonatal intestinal emergencies that affect premature infants. Although most cases of early NEC can be successfully managed with medical therapy, prompt surgical intervention is often required for advanced or perforated NEC and FIP. METHODS The surgical management and treatment of FIP and NEC are discussed on the basis of literature review and our personal experience. RESULTS Surgical options are diverse, and include peritoneal drainage, laparotomy with diverting ostomy alone, laparotomy with intestinal resection and primary anastomosis or stoma creation, with or without second-look procedures. CONCLUSIONS The optimal surgical therapy for FIP and NEC begins with prompt diagnosis and adequate fluid resuscitation. It appears that there is no significant difference in patient outcome based on surgical management alone. However, the infant's weight, comorbidities, surgeon preference and timing of intervention should be taken into account before operative intervention.
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Abstract
Necrotizing enterocolitis (NEC) remains a major cause of morbidity and death in neonates. The 30% to 50% mortality rate for NEC with perforation has not changed appreciably in the past 30 years. The critical relevant outcomes following NEC include survival, gastrointestinal function, and neurodevelopmental status. In each of these areas, initial anecdotal and case-series analysis has been followed by studies using more sophisticated methods of analysis. The single most important predictor of outcome, besides gestational age, is whether or not the disease has progressed to the point requiring surgical intervention. Patients with NEC requiring operation have a high mortality. Moreover, the vast majority of morbidity following NEC occurs in the patients who survive following operation. The purpose of this review is to examine the evolution of evidence regarding outcomes for patients with NEC and to provide an update on our current state of knowledge.
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Affiliation(s)
- Marion C W Henry
- Section of Pediatric Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA
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