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Tu IWH, Chan EEH, Laksmi NK. Ileo-ileal intussusception and necrotising enterocolitis after indomethacin exposure masquerading clinically as solitary intestinal perforation. BMJ Case Rep 2025; 18:e263126. [PMID: 39809488 DOI: 10.1136/bcr-2024-263126] [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] [Indexed: 01/16/2025] Open
Abstract
We report a case of small bowel perforation from ileo-ileal intussusception with necrotising enterocolitis (NEC) after indomethacin exposure mimicking spontaneous intestinal perforation in an extremely preterm neonate. Indomethacin exposure can cause mesenteric hypoperfusion, resulting in an ischaemic lead point for intussusception and NEC. We advocate that intussusception should be considered as one of the differentials for neonates with recurrent feeding intolerance postindomethacin exposure. Diagnosis with early ultrasound by an experienced sonographer is crucial for timely surgical reduction to prevent intestinal perforation.
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Affiliation(s)
- Irene Wen Hui Tu
- Department of Paediatric Surgery, KK Women's and Children's Hospital, Singapore
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2
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Hudson JABJ, Shabbir W, Hayawi LM, Chan MLM, Barrowman N, Sikora L, Ferretti E. Use of NSAIDs and acetaminophen and risk of spontaneous intestinal perforations in premature infants: a systematic review and meta-analysis. Front Pediatr 2024; 12:1450121. [PMID: 39649405 PMCID: PMC11620902 DOI: 10.3389/fped.2024.1450121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 10/09/2024] [Indexed: 12/10/2024] Open
Abstract
Background Acquired spontaneous intestinal perforation or SIP occurs most commonly in the extremely premature infant population. As the incidence is rising, understanding modifiable factors such as common medication exposures becomes important for individualizing care. Methods The primary outcome was SIP in premature infants with exposure to indomethacin, ibuprofen, or acetaminophen. The systematic review and meta-analysis were conducted following the Cochrane methodology and PRISMA guidelines. Results The point estimates of three RCTs showed an increase in the risk of SIP with indomethacin exposure compared to no medication, the pooled estimate was not statistically significant. There is no statistically significant association between the risk of SIP for indomethacin with treatment use over prophylactic use and when holding feeds. Ibuprofen conferred less risk than indomethacin, and its route of administration did not alter the risk profile. There was not enough evidence to draw conclusions about the risk of SIP and acetaminophen exposure. Conclusion In studies of infants exposed to either indomethacin or ibuprofen in the last 40 years, the incidence of SIP is still commonly within 2-8%. Moving forward modifiable factors such as medication exposure will help guide care to minimize risk where possible. Systematic Review Registration https://www.crd.york.ac.uk/, PROSPERO (CRD42017058603).
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Affiliation(s)
- Jo-Anna B. J. Hudson
- Department of Pediatrics, Division of Neonatology, Memorial University, St. John's, Newfoundland, NF, Canada
- Department of OBGYN, Newborn Division, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada
- Department of Pediatrics, Division of Neonatology, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
| | - Wardha Shabbir
- Department of Family Medicine, Michigan State University, Jackson, MI, United States
| | - Lamia M. Hayawi
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - Monica Lik Man Chan
- Department of OBGYN, Newborn Division, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada
| | - Nicholas Barrowman
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - Lindsey Sikora
- Health Sciences Library, University of Ottawa, Ottawa, ON, Canada
| | - Emanuela Ferretti
- Department of OBGYN, Newborn Division, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada
- Department of Pediatrics, Division of Neonatology, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
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Harsha N, Mendu SB, Santhosh A, Kotha R, Alimelu M. An Early Presentation of Spontaneous Intestinal Perforation in a Very Low Birth Weight Neonate: A Case Report. Cureus 2023; 15:e42285. [PMID: 37609093 PMCID: PMC10440627 DOI: 10.7759/cureus.42285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/21/2023] [Indexed: 08/24/2023] Open
Abstract
Pneumoperitoneum is typically caused by breached hollow viscera and necessitates surgical intervention. This may have various etiologies, including spontaneous, necrotizing enterocolitis (NEC), and obstruction. In these cases, spontaneous intestinal perforation (SIP) is a unique clinical entity with a better outcome than newborns with NEC-related intestinal perforation. Here, we present a rare case of SIP manifested in the form of pneumoperitoneum in the first eight hours of life, emphasizing the importance of differentiation between NEC and SIP, as each condition has variable treatment options and outcome considerations.
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Affiliation(s)
- Neelam Harsha
- Department of Neonatology, Niloufer Hospital, Hyderabad, IND
| | | | - Avinash Santhosh
- Department of Pediatrics Intensive Care, Osmania Medical College, Hyderabad, IND
| | - Rakesh Kotha
- Department of Neonatology, Osmania Medical College, Hyderabad, IND
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Donà D, Gastaldi A, Barbieri E, Bonadies L, Aluvaala J, English M. Empirical Antimicrobial Therapy of Neonates with Necrotizing Enterocolitis: A Systematic Review. Am J Perinatol 2021; 40:646-656. [PMID: 34126646 PMCID: PMC7614399 DOI: 10.1055/s-0041-1730364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE Necrotizing enterocolitis (NEC) is an inflammatory disease of the gastrointestinal tract characterized by ischemic necrosis of the intestinal mucosa, mostly affecting premature neonates. Management of NEC includes medical care and surgical approaches, with supportive care and empirical antibiotic therapy recommended to avoid any disease progression. However, there is still no clear evidence-based consensus on empiric antibiotic strategies or surgical timing. This study was aimed to review the available evidence on the effectiveness and safety of different antibiotic regimens for NEC. STUDY DESIGN MEDLINE, EMBASE, Cochrane CENTRAL, and CINAHL databases were systematically searched through May 31, 2020. Randomized controlled trials (RCTs) and nonrandomized interventions reporting data on predefined outcomes related to NEC treatments were included. Clinical trials were assessed using the criteria and standard methods of the Cochrane risk of bias tool for randomized trials, while the risk of bias in nonrandomized studies of interventions was evaluated using the ROBINS-I tool. The certainty in evidence of each outcome's effects was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS Five studies were included in this review, two RCTs and three observational studies, for a total amount of 3,161 patients. One RCT compared the outcomes of parenteral (ampicillin plus gentamicin) and oral (gentamicin) treatment with parenteral only. Three studies (one RCT and two observational) evaluated adding anaerobic coverage to different parenteral regimens. The last observational study compared two different parenteral antibiotic combinations (ampicillin and gentamicin vs. cefotaxime and vancomycin). CONCLUSION No antimicrobial regimen has been shown to be superior to ampicillin and gentamicin in decreasing mortality and preventing clinical deterioration in NEC. The use of additional antibiotics providing anaerobic coverage, typically metronidazole, or use of other broad-spectrum regimens as first-line empiric therapy is not supported by the very limited current evidence. Well-conducted, appropriately sized comparative trials are needed to make evidence-based recommendations. KEY POINTS · Ampicillin and gentamicin are effective in decreasing mortality and preventing clinical deterioration in NEC.. · Metronidazole could be added in patients with surgical NEC.. · No study with high-quality evidence was found..
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Affiliation(s)
- Daniele Donà
- Division of Paediatric Infectious Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy
| | - Andrea Gastaldi
- Department of Pediatrics, Woman and Child Hospital, University of Verona, Verona, Italy
| | - Elisa Barbieri
- Division of Paediatric Infectious Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy
| | - Luca Bonadies
- Neonatal Intensive Care Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy
| | - Jalemba Aluvaala
- Health Services Unit, KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya.,Department of Paediatrics, University of Nairobi, Nairobi, Kenya
| | - Mike English
- Health Services Unit, KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya.,Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom
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5
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Moser MF, Müller IJ, Schalamon J, Resch B. Neurodevelopmental outcome of very preterm infants with gastrointestinal tract perforations does not differ compared to controls. Wien Klin Wochenschr 2021; 133:680-686. [PMID: 34110498 PMCID: PMC8292234 DOI: 10.1007/s00508-021-01886-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 04/24/2021] [Indexed: 10/24/2022]
Abstract
PURPOSE To evaluate gastrointestinal tract (GIT) perforations in very low birth weight infants and the effects on neurodevelopmental outcome. METHODS Between 2000 and 2017 all cases with GIT perforation were analyzed regarding causes, associated morbidities and neurodevelopmental outcome and compared with matched (gestational age, birth weight, gender, year of birth) by 1:2 controls. RESULTS The incidence of GIT perforation was 2.0% (n = 38/1878). Diagnoses associated with GIT were meconium obstruction of prematurity (MOP,n = 19/50%), spontaneous intestinal perforation (SIP, n = 7/18%), necrotizing enterocolitis (NEC, n = 6/16%), iatrogenic perforation (n = 3/8%), volvulus (n = 2/5%) and meconium ileus (n = 1/3%). The NEC-associated perforations occurred later compared to those associated with MOP and SIP (median 8 days and 6 days vs. 17 days, p = 0.001 and 0.023, respectively) and main localization was the terminal ileum (84%). Cases had higher rates of late onset sepsis (55% vs. 24%, p = 0.003), longer duration of mechanical ventilation (median 30 days vs 18 days, p = 0.013) and longer stays at the hospital (median 122 days vs 83 days, p < 0.001); mortality rates did not differ. The 2‑year neurodevelopment follow-up revealed no differences between groups (normal development 49% vs. 40%). CONCLUSION Despite increased morbidities preterm infants with GIT perforation did not have a higher mortality rate and groups did not differ regarding neurodevelopmental outcome at the corrected for prematurity age of 2 years.
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Affiliation(s)
- Michael F Moser
- Research Unit for Neonatal Infectious Diseases and Epidemiology, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria
| | - Irina J Müller
- Research Unit for Neonatal Infectious Diseases and Epidemiology, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria
| | - Johannes Schalamon
- Division of Pediatric Surgery, Department of Pediatric and Adolescent Surgery, Medical University of Graz, Auenbruggerplatz 34/1, 8036, Graz, Austria
| | - Bernhard Resch
- Research Unit for Neonatal Infectious Diseases and Epidemiology, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria. .,Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria.
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Huang Y, Wu Y, Jin D, Tang Q, Yuan P, Lu Q. Development and Validation of a Nomogram for Preoperative Prediction of Localization of Neonatal Gastrointestinal Perforation. Front Pediatr 2021; 9:754623. [PMID: 34796155 PMCID: PMC8593177 DOI: 10.3389/fped.2021.754623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/06/2021] [Indexed: 12/30/2022] Open
Abstract
Background: Information regarding the localization of gastrointestinal perforation is crucial for the following surgical procedure. This study was to determine the key indicators and develop a prediction model for the localization in neonates with gastrointestinal perforation. Methods: A nomogram to predict the location of neonatal gastrointestinal perforation was developed using a cohort of patients who underwent surgery between July 2009 and May 2021. Baseline variables were analyzed using logistics regression and nomogram developed using significant predictors. The predictive performance of the nomogram was assessed by the concordance index (C-index), calibration curve, and area under the receiver operating characteristic (ROC) curve (AUC). The nomogram was further validated in an integrated external cohort. Results: We investigated the data of 201 patients, of which 65 (32.3%) were confirmed with upper gastrointestinal perforation by surgery. Multivariate logistic regression analysis identified the following as independent predictors: preterm [OR: 5.014 (1.492-18.922)], time of onset [OR: 0.705 (0.582-0.829)], preoperative hemoglobin [OR:1.017 (1.001-1.033)], bloody stool: No [OR: 4.860 (1.270-23.588)], shock [OR: 5.790 (1.683-22.455)] and sepsis: No [OR 3.044 (1.124-8.581)]. Furthermore, the nomogram was effective in predicting the perforation site, with an AUC of 0.876 [95% confidence interval (CI): 0.830-0.923]. Internal validation showed that the average AUC was 0.861. Additionally, the model achieved satisfactory discrimination (AUC, 0.900; 95% CI, 0.826-0.974) and calibration (Hosmer-Lemeshow test, P = 0.4802) in external validation. Conclusions: The nomogram based on the six factors revealed good discrimination and calibration, suggesting good clinical utility. The nomogram could help surgeons predict the location of gastrointestinal perforation before surgery to make a surgical plan.
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Affiliation(s)
- Yao Huang
- Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Yuhua Wu
- Department of Neonatology, The General Hospital of Ningxia Medical University, Ningxia, China
| | - Dongmei Jin
- Department of Neonatology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qing Tang
- Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Peng Yuan
- Department of Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Qi Lu
- Department of Neonatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
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Seo YM, Lin YK, Im SA, Sung IK, Youn YA. Interleukin 8 may predict surgical necrotizing enterocolitis in infants born less than 1500 g. Cytokine 2020; 137:155343. [PMID: 33128923 DOI: 10.1016/j.cyto.2020.155343] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 09/26/2020] [Accepted: 10/08/2020] [Indexed: 11/16/2022]
Abstract
Necrotizing enterocolitis (NEC) often leads to gastrointestinal emergency resulting high mortality in very low birth weight infants (VLBWIs) requiring surgery. To date, few studies have explored the role of serum cytokines in the development of feeding intolerance (FI) or NEC outcomes in VLBWIs. Infants born weighing <1500 g or of 32 weeks of gestational age were prospectively enrolled from May 2018 to Dec 2019. We measured several cytokines routinely within 72 h of life, even before NEC-like symptoms developed. NEC or FI group comprised 17 (27.4%) infants, and 6 (9.7%) infants had surgical NEC. The gestational age and birth weight were significantly lower in the NEC or FI group with more prematurity-related complications. The surgical NEC group also demonstrated significantly lower gestational age and birth weight along with more infants experiencing refractory hypotension within a 1 week of life, pulmonary hypertension, and patent ductus arteriosus. IL-10 levels were significantly higher in the NEC or FI group, whereas IL-8 levels were significantly higher in the infants with surgical NEC. Our findings indicated to IL-8 can predict surgical NEC while increased IL-10 can predict NEC development in VLBWIs.
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MESH Headings
- Biomarkers/blood
- Cytokines/blood
- Enterocolitis, Necrotizing/blood
- Enterocolitis, Necrotizing/diagnosis
- Enterocolitis, Necrotizing/surgery
- Gestational Age
- Humans
- Infant
- Infant, Newborn
- Infant, Premature/blood
- Infant, Premature, Diseases/blood
- Infant, Premature, Diseases/diagnosis
- Infant, Premature, Diseases/surgery
- Infant, Very Low Birth Weight/blood
- Inflammation Mediators/blood
- Interleukin-10/blood
- Interleukin-8/blood
- Prognosis
- Prospective Studies
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Affiliation(s)
- Yu-Mi Seo
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yen-Kuang Lin
- Research Center of Biostatistics, Taipei Medical University, Taipei City 106, Taiwan
| | - Soo-Ah Im
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - In-Kyung Sung
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young-Ah Youn
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Ahle S, Badru F, Damle R, Osei H, Munoz-Abraham AS, Bajinting A, Barbian ME, Bhatia AM, Gingalewski C, Greenspon J, Hamilton N, Stitelman D, Strand M, Warner BW, Villalona GA. Multicenter retrospective comparison of spontaneous intestinal perforation outcomes between primary peritoneal drain and primary laparotomy. J Pediatr Surg 2020; 55:1270-1275. [PMID: 31383579 DOI: 10.1016/j.jpedsurg.2019.07.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 07/05/2019] [Accepted: 07/10/2019] [Indexed: 11/24/2022]
Abstract
PURPOSE The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy. METHODS We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy. RESULTS We identified 171 patients treated for SIP (drain n = 110 vs. laparotomy n = 61). There were no differences in maternal or prenatal characteristics. There were no clinically significant differences in vital signs, white blood cell or platelet measures, up to 48 h after intervention. Patients who were treated primarily with a drain were more premature (24.9 vs. 27.2 weeks, p < 0.001) and had lower median birth weight (710 g vs. 896 g, p < 0.001). No significant differences were found in complications, time to full feeds, length of stay (LOS) or mortality between the groups. Primary laparotomy group had more procedures (median number 1 vs. 2, p = 0.002). There were 32 (29%) primary drain failures whereby a laparotomy was ultimately needed. CONCLUSIONS SIP treated with primary drain is successful in the majority of patients with no significant differences in outcomes when compared to laparotomy with stoma. THE LEVEL OF EVIDENCE III.
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Affiliation(s)
- Samantha Ahle
- Section of Pediatric Surgery, Yale University School of Medicine/Yale-New haven Hospital, New Haven, CT.
| | - Faidah Badru
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO; Saint Louis University School of Medicine, Saint Louis, MO
| | - Rachelle Damle
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO
| | - Hector Osei
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO
| | - Armando Salim Munoz-Abraham
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO
| | - Adam Bajinting
- Section of Pediatric Surgery, Randall Children's Hospital at Legacy Emanuel, Portland, OR
| | | | - Amina M Bhatia
- Section of Pediatric Surgery, Children's Healthcare of Atlanta, Atlanta, GA
| | - Cindy Gingalewski
- Section of Pediatric Surgery, Oregon Health and Science University, Portland, OR
| | - Jose Greenspon
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO
| | - Nicholas Hamilton
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
| | - David Stitelman
- Section of Pediatric Surgery, Yale University School of Medicine/Yale-New haven Hospital, New Haven, CT
| | - Marya Strand
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO
| | - Brad W Warner
- Division of Pediatric Surgery, Washington University School of Medicine/Saint Louis Children's Hospital, St. Louis, MO
| | - Gustavo A Villalona
- Section of Pediatric Surgery, Saint Louis University/Cardinal Glennon Children's Medical Center, St. Louis, MO
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Role of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review. Nutrients 2020; 12:nu12051347. [PMID: 32397283 PMCID: PMC7284579 DOI: 10.3390/nu12051347] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 04/27/2020] [Accepted: 04/28/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Spontaneous intestinal perforation (SIP) is a devastating complication of prematurity, and extremely low birthweight (ELBW < 1000 g) infants born prior to 28 weeks are at highest risk. The role of nutrition and feeding practices in prevention and complications of SIP is unclear. The purpose of this review is to compile evidence to support early nutrition initiation in infants at risk for and after surgery for SIP. Methods: A search of PubMed, EMBASE and Medline was performed using relevant search terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstracts and full texts were reviewed by co-first authors. Studies with infants diagnosed with SIP that included information on nutrition/feeding practices prior to SIP and post-operatively were included. Primary outcome was time to first feed. Secondary outcomes were incidence of SIP, time to full enteral feeds, duration of parenteral nutrition, length of stay, neurodevelopmental outcomes and mortality. Results: Nineteen articles met inclusion criteria—nine studies included feeding/nutrition data prior to SIP and ten studies included data on post-operative nutrition. Two case series, one cohort study and sixteen historical control studies were included. Three studies showed reduced incidence of SIP with initiation of enteral nutrition in the first three days of life. Two studies showed reduced mortality and neurodevelopmental impairment in infants with early feeding. Conclusions: Available data suggest that early enteral nutrition in ELBW infants reduces incidence of SIP without increased mortality.
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10
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Barseghyan K, Gayer C, Azhibekov T. Differences in Serum Alkaline Phosphatase Levels in Infants with Spontaneous Intestinal Perforation versus Necrotizing Enterocolitis with Perforation. Neonatology 2020; 117:349-357. [PMID: 32750698 DOI: 10.1159/000509617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 06/21/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Data on laboratory markers of spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) remain sparse. OBJECTIVE To compare serum alkaline phosphatase levels in infants with bowel perforation secondary to SIP versus surgical NEC, and then investigate the possible role of serum alkaline phosphatase in differentiating infants with these conditions. METHODS A retrospective case-control study of infants admitted with bowel perforation from 2005 to 2015. Demographic and prenatal data, postnatal exposures, and clinical, laboratory, and radiographic findings were extracted from inpatient medical records and analyzed using regression analysis. RESULTS Of 114 outborn infants included, 48 infants had SIP (cases) and 66 had NEC (controls). Upon admission from the referring hospital, the serum alkaline phosphatase level was significantly higher in infants with SIP, i.e., a median value of 782 versus236 U/L in NEC patients (p < 0.0001), with an adjusted odds ratio (OR) of 4.3 (p < 0.05) when the level was >500 U/L in multivariate regression model. Infants with SIP had significantly younger gestational age, presented earlier in life, primarily with pneumoperitoneum, and had greater exposure to steroids and indomethacin compared to infants with NEC. Alkaline phosphatase levels decreased rapidly in infants with SIP following admission. CONCLUSION A transient increase in serum alkaline phosphatase level is independently associated with SIP when compared to NEC. Studies to confirm the role of alkaline phosphatase in the diagnosis of SIP are necessary and have potentially significant clinical and prognostic implications.
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Affiliation(s)
- Karine Barseghyan
- Division of Neonatology, LAC+USC Medical Center/Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.,Kaiser Permanente Panorama City and Woodland Hills Medical Centers, Los Angeles, California, USA
| | - Christopher Gayer
- Division of Pediatric Surgery, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Timur Azhibekov
- Division of Neonatology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California Los Angeles, Los Angeles, California, USA, .,Division of Neonatology, Department of Pediatrics, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA,
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11
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Rovers JFJ, Thomissen IJC, Janssen LCE, Lingius S, Wieland BV, Dieleman JP, Niemarkt HJ, van Runnard Heimel PJ. The relationship between antenatal indomethacin as a tocolytic drug and neonatal outcomes: a retrospective cohort study. J Matern Fetal Neonatal Med 2019; 34:2945-2951. [PMID: 31597542 DOI: 10.1080/14767058.2019.1674807] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
INTRODUCTION Preterm birth is associated with increased mortality and morbidity. Tocolytic drugs, such as indomethacin, are often used to postpone preterm delivery. Indomethacin has been proven to be more effective than other tocolytic agents in terms of delaying birth but is often prescribed with caution because of its potential association with adverse neonatal outcomes. We aim to study the effects of antenatal indomethacin on neonatal outcomes after controlling for potential confounders, as compared to nifedipine and/or atosiban. METHODS In this cohort study, we performed a retrospective analysis of maternal and neonatal data. Women were included if they received indomethacin, nifedipine or atosiban as a tocolytic drug for imminent preterm labor and gave birth at a gestational age (GA) between 235/7 and 320/7 weeks, between 2010 and 2015. Main outcome measures were: neonatal death, necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), patent ductus arteriosus (PDA) and its treatment. RESULTS Four hundred seventy-four women, delivering 610 infants were investigated. The incidence of the following adverse neonatal outcomes were significantly higher after indomethacin use: neonatal death (p = .017), NEC (p = .026), SIP (p = .008), PDA (p = .000) and PDA ligation (p = .000). However, these associations showed to be nonsignificant after adjusting for confounders (adjusted odds ratio neonatal mortality 1.6 (0.7-3.8)), NEC 1.6 (0.6-4.4), SIP 2.8 (0.3-30.0), PDA 1.1 (0.6-2.2) and PDA ligation 2.2 (0.7-6.5). CONCLUSIONS The presumed association between antenatal indomethacin exposure and several adverse neonatal outcomes may be based upon indication bias. Taking important confounding factors, such as GA at birth and neonatal birth weight into account, antenatal indomethacin exposure does not result in a higher incidence of adverse neonatal outcomes. However, there may be a higher risk for spontaneous intestinal perforation.
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Affiliation(s)
- Jessica F J Rovers
- Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven, The Netherlands
| | | | - Lobke C E Janssen
- Department of Pediatrics, VieCuri Medical Center, Venlo, The Netherlands
| | - Sjane Lingius
- Department of Obstetrics and Gynecology, Zaans Medisch Centrum, Zaandam, The Netherlands
| | - Bernice V Wieland
- Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven, The Netherlands
| | - Jeanne P Dieleman
- Máxima Medical Center, Máxima Medical Center Academy, Veldhoven, The Netherlands
| | - Hendrik J Niemarkt
- Máxima Medical Center, Neonatal Intensive Care Unit, Veldhoven, The Netherlands
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12
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Murphy T, Yang S, Tucker R, Collyer H, Kurkchubasche AG, Bender J. Necrotizing Enterocolitis and Spontaneous Intestinal Perforation: A Spatiotemporal Case Cluster Analysis. Pediatr Qual Saf 2019; 4:e127. [PMID: 30937409 PMCID: PMC6426488 DOI: 10.1097/pq9.0000000000000127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 11/07/2018] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE To expand existing statistical methods to identify clusters of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) cases in the neonatal intensive care unit. METHODS In an academic, tertiary referral center, possible NEC or SIP clusters were identified using a binomial distribution scan test. The incidence-density rate (IDR) was calculated as the number of cases per 1,000 patient-days during each possible cluster and compared with the baseline IDR. A structured chart review compared cluster and noncluster cases. Spatial clustering analyzed the physical distribution of cases using the Grimson Test. Repeat analysis included only SIP cases. RESULT The initial scan identified 3 suspected temporal clusters. IDR comparison confirmed only 1 cluster. Analysis of SIP only cases revealed similar results. Physical proximity was not a significant factor. Chart review of the SIP and NEC cases revealed significant increases during the confirmed cluster of small for gestational age infant births and indomethacin treatment. Chart review of the SIP only cases in the confirmed cluster revealed no significant differences. CONCLUSION Statistical methods distinguish whether suspected case clusters represent a significant increase in baseline incidence. True clusters warrant detailed investigation including spatial analysis and chart review. This approach may have application in other disease processes and populations.
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Affiliation(s)
- Thomas Murphy
- From the Department of Pediatrics, Women & Infants Hospital, Alpert Medical School of Brown University
| | - Samuel Yang
- From the Department of Pediatrics, Women & Infants Hospital, Alpert Medical School of Brown University
| | - Richard Tucker
- From the Department of Pediatrics, Women & Infants Hospital, Alpert Medical School of Brown University
| | - Hillary Collyer
- Division of Pediatric Surgery, Hasbro Children’s Hospital, Alpert Medical School of Brown University, Providence, RI
| | - Arlet G. Kurkchubasche
- Division of Pediatric Surgery, Hasbro Children’s Hospital, Alpert Medical School of Brown University, Providence, RI
| | - Jesse Bender
- From the Department of Pediatrics, Women & Infants Hospital, Alpert Medical School of Brown University
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13
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The role of imaging in the management of necrotising enterocolitis: a multispecialist survey and a review of the literature. Eur Radiol 2018; 28:3621-3631. [PMID: 29582131 PMCID: PMC6096607 DOI: 10.1007/s00330-018-5362-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 01/26/2018] [Accepted: 01/30/2018] [Indexed: 01/04/2023]
Abstract
Objectives To investigate current practices and perceptions of imaging in necrotising enterocolitis (NEC) according to involved specialists, put them in the context of current literature, and identify needs for further investigation. Methods Two hundred two neonatologists, paediatric surgeons, and radiologists answered a web-based questionnaire about imaging in NEC at their hospitals. The results were descriptively analysed, using proportion estimates with 95% confidence intervals. Results There was over 90% agreement on the value of imaging for confirmation of the diagnosis, surveillance, and guidance in decisions on surgery as well as on abdominal radiography as the first-choice modality and the most important radiographic signs. More variation was observed regarding some indications for surgery and the use of some ultrasonographic signs. Fifty-eight per cent stated that ultrasound was used for NEC at their hospital. Examination frequency, often once daily or more but with considerable variations, and projections used in AR were usually decided individually rather than according to fixed schedules. Predicting the need of surgery was regarded more important than formal staging. Conclusion Despite great agreement on the purposes of imaging in NEC and the most important radiographic signs of the disease, there was considerable diversity in routines, especially regarding examination frequency and the use of ultrasound. Apart from continuing validation of ultrasound, important objectives for future studies include definition of the supplementary roles of both imaging modalities in relation to other diagnostic parameters and evaluation of various imaging routines in relation to timing of surgery, complications, and mortality rate. Key Points • Imaging is an indispensable tool in the management of necrotising enterocolitis • Predicting the need of surgery is regarded more important than formal staging • There is great consensus on important signs of NEC on abdominal radiography • There is more uncertainty regarding the role of ultrasound • Individualised management is preferred over standardised diagnostic algorithms Electronic supplementary material The online version of this article (10.1007/s00330-018-5362-x) contains supplementary material, which is available to authorized users.
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14
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Iacusso C, Boscarelli A, Fusaro F, Bagolan P, Morini F. Pathogenetic and Prognostic Factors for Neonatal Gastric Perforation: Personal Experience and Systematic Review of the Literature. Front Pediatr 2018; 6:61. [PMID: 29670869 PMCID: PMC5893822 DOI: 10.3389/fped.2018.00061] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 03/02/2018] [Indexed: 01/17/2023] Open
Abstract
INTRODUCTION Neonatal gastric perforation (NGP) is a rare entity. Our aim was to report our experience and review the recent literature to characterize NGP, describe associated factors, and define prognostic factors. MATERIALS AND METHODS Retrospective review of all consecutive patients with NGP treated between June 2009 and December 2017 in a third level pediatric hospital. In addition, a systematic review of Medline and Scopus database was performed using a defined strategy. All articles referring to NGP published between 2005 and 2017 were retrieved. Variables considered: prematurity (<37 weeks gestation), birth weight (BW), Apgar score, prenatal complications, age at diagnosis, bag ventilation, pathogenetic events, site of perforation, treatment of perforation, sepsis, and outcome. Mann-Whitney or Fisher's test were used as appropriate. Results are median (range) or prevalence. RESULTS Between 2009 and 2016 we treated 8 consecutive patients for NGP and 199 further cases were retrieved from the systematic review (total of 207 patients). Overall survival was 73%. Most frequently reported pathogenesis: iatrogenic (20 patients), hypoxic/ischemic or infection stress (13 patients), duodenal/jejunal obstruction (11 patients), drugs (11 patients), esophageal atresia (10 patients). 60% patients had only primary repair of the perforation as gastric surgery. Sepsis developed in 56 patients (34%). CONCLUSION Although the pathogenesis of NGP is pleomorphic, prematurity and low BWs are frequent in these patients. Reviewing our experience and the available literature, none of the variables considered, but sepsis was associated with mortality.
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Affiliation(s)
- Chiara Iacusso
- Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Alessandro Boscarelli
- Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Fabio Fusaro
- Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Pietro Bagolan
- Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Francesco Morini
- Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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15
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Mugarab-Samedi V, Howlett A, Hicks M, Arrieta MC, Beaudry P, Dersch-Mills D, Alshaikh B. Probiotics supplementation and length of hospital stay in neonates with gastrointestinal surgery. Int J Surg Protoc 2017; 6:13-16. [PMID: 31851737 PMCID: PMC6913565 DOI: 10.1016/j.isjp.2017.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 10/05/2017] [Accepted: 10/06/2017] [Indexed: 11/18/2022] Open
Abstract
Any manipulation on open bowel causes interventional impact on gut microbiome, and surgical stress triggers bacterial translocation; thus, it will be fundamental to determine gut microbiome after surgery. Monitoring dynamic changes in microbiome of post-surgical infants who received probiotics and placebo could provide with important information about gut colonization and potential bacterial overgrowth. The purpose of this study is to assess the effect of probiotics supplementation on length of hospital stay, duration of parenteral nutrition, and feed tolerance in neonates after gastrointestinal surgery.
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Affiliation(s)
| | - Alixe Howlett
- Department of pediatrics, University of Calgary, Calgary, Canada
| | - Mattew Hicks
- Department of pediatrics, University of Alberta, Edmonton, Canada
| | | | - Paul Beaudry
- Department of pediatrics, University of Calgary, Calgary, Canada
| | | | - Belal Alshaikh
- Department of pediatrics, University of Calgary, Calgary, Canada
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16
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Downey LC, Cotten CM, Hornik CP, Laughon MM, Tolia VN, Clark RH, Smith PB. Association of in utero magnesium exposure and spontaneous intestinal perforations in extremely low birth weight infants. J Perinatol 2017; 37:641-644. [PMID: 28125094 PMCID: PMC5446291 DOI: 10.1038/jp.2016.274] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 11/03/2016] [Accepted: 11/23/2016] [Indexed: 11/20/2022]
Abstract
OBJECTIVE The objective of this study is to determine whether antenatal exposure to magnesium is associated with spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants (⩽1000 g). STUDY DESIGN We identified all ELBW infants admitted to 1 of 323 neonatal intensive care units from 2007 to 2013. We used multivariable conditional logistic regression to compare outcomes in the first 21 days after birth between infants exposed and unexposed to magnesium in utero. RESULTS Of the 28 035 infants, 11 789 (42%) were exposed to antenatal magnesium (AM). There was no difference in the risk of SIP, odds ratio=1.08 (95% confidence interval; 0.91 to 1.29), between infants exposed and unexposed to AM. Mortality in the first 21 days after birth was lower in the magnesium-exposed infants, odds ratio=0.76 (0.70 to 0.83). CONCLUSION AM exposure in ELBW infants was not associated with increased risk of SIP.
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Affiliation(s)
- L. Corbin Downey
- Division of Neonatology, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC
| | - C. Michael Cotten
- Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, NC
| | - Christoph P. Hornik
- Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, NC
| | - Matthew M. Laughon
- Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill
| | - Veeral N. Tolia
- Pediatrix Medical Group and Baylor University Medical Center, Dallas, TX
| | - Reese H. Clark
- Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL
| | - P. Brian Smith
- Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, NC
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17
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Prgomet S, Lukšić B, Pogorelić Z, Jurić I, Čapkun V, Arapović A, Boban N. Perinatal risk factors in newborns with gastrointestinal perforation. World J Gastrointest Surg 2017; 9:46-52. [PMID: 28289509 PMCID: PMC5329703 DOI: 10.4240/wjgs.v9.i2.46] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 11/10/2016] [Accepted: 12/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate correlation of perinatal risk factors in newborns with gastrointestinal perforation (GIP).
METHODS Single-center retrospective cohort study was conducted between January 1990 and December 2012. Medical records on all newborns with GIP were reviewed (n = 35). Surgical records and histopathologic examination of all perforated intestine samples were also reviewed.
RESULTS The most common cause of GIP was necrotizing enterocolitis (51.4%). The most common site of perforation was large intestine. Mortality rate was 31%. Infants with GIP more frequently had very low birth weight (< 1500 g), especially birth weight below 10th percentile according to gestational age. Ponderal index was not differing between infants with GIP and control subjects. In infants with GIP anemia was more frequently found than in control group.
CONCLUSION GIP in newborns is mostly disease of infants with birth weight below 10th percentile according to gestational age. GIP occurs more often in infants with anemia.
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18
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Hubertus J, von Schweinitz D. Nekrotisierende Enterokolitis und Kurzdarmsyndrom. Monatsschr Kinderheilkd 2016. [DOI: 10.1007/s00112-016-0153-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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19
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Al‐lawama M, Al‐Momani HM, AboKwaik WM, Al‐zaben KR. Benign pneumoperitoneum in newborns: which abdomen to open and which one to observe? Clin Case Rep 2016; 4:561-3. [PMID: 27398197 PMCID: PMC4891479 DOI: 10.1002/ccr3.569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 02/27/2016] [Accepted: 04/03/2016] [Indexed: 11/30/2022] Open
Abstract
Benign pneumoperitoneum in newborns is not a rare condition that should be managed conservatively. Neonatologists and surgical teams should work together to avoid unnecessary and potentially risky procedures.
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Affiliation(s)
- Manar Al‐lawama
- Neonatal‐Perinatal MedicineThe University of JordanAmman11937Jordan
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20
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Bowel Perforation in Premature Infants with Necrotizing Enterocolitis: Risk Factors and Outcomes. Gastroenterol Res Pract 2016; 2016:6134187. [PMID: 27375739 PMCID: PMC4916290 DOI: 10.1155/2016/6134187] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Revised: 04/18/2016] [Accepted: 05/17/2016] [Indexed: 12/21/2022] Open
Abstract
We aim to determine risk factors and clinical outcomes for bowel perforation in premature infants with NEC. We analyzed clinical data of 57 cases of premature infants with NEC at our NICU between January 2010 and December 2012. Based on the presence of bowel perforation, we divided these infants into two groups: perforated NEC group (n = 10) and nonperforated NEC group (n = 47). We compared general information, clinical characteristics, and laboratory findings between groups. The perforated NEC group, compared to the nonperforated NEC group, had significantly lesser gestational age, lower birth weight, higher prevalence of apnea, mechanical ventilation, sepsis and shock, lower blood pH, higher levels of blood glucose, abnormal WBC count and thrombocytopenia, and elevated CRP (all P < 0.05). Moreover, the perforated NEC group had significantly longer durations of fasting and TPN usage, higher incidences of EUGR and cholestasis, longer duration of antibiotics, higher frequency of advanced antibiotics use, and poorer prognosis than the nonperforated NEC group (all P < 0.05). Bowel perforation in premature infants with NEC was associated with multiple risk factors. Early identification of some of these risk factors in premature infants with NEC may help implement early intervention to reduce the incidence of bowel perforation and thereby improve the prognosis.
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21
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Abstract
Necrotizing enterocolitis is a devastating intestinal disease that affects ~5% of preterm neonates. Despite advancements in neonatal care, mortality remains high (30–50%) and controversy still persists with regards to the most appropriate management of neonates with necrotizing enterocolitis. Herein, we review some controversial aspects regarding the epidemiology, imaging, medical and surgical management of necrotizing enterocolitis and we describe new emerging strategies for prevention and treatment.
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Affiliation(s)
- Augusto Zani
- Division of General and Thoracic Surgery, University of Toronto, The Hospital for Sick Children, Toronto, Canada
| | - Agostino Pierro
- Division of General and Thoracic Surgery, University of Toronto, The Hospital for Sick Children, Toronto, Canada
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22
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Müller B, Stahr N, Knirsch W, Hoigné I, Frey B. Bubbles in the heart as first sign of gastric pneumatosis. Eur J Pediatr 2014; 173:1587-9. [PMID: 23955485 DOI: 10.1007/s00431-013-2129-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 07/30/2013] [Indexed: 11/30/2022]
Abstract
UNLABELLED This case report describes a 5-week-old boy with an unusual presentation of gastric pneumatosis caused by suspected necrotizing enterocolitis (NEC) after cardiogenic shock. Postnatally, a pulmonary atresia with intact ventricular septum was supplied by a modified Blalock-Taussig shunt. On transthoracic echocardiography in week 5, primarily performed to rule out pericardial effusion, air bubbles have been apparent in the right atrium. Intracardiac air found on echocardiogram is generally associated with an indwelling venous catheter but-as exemplified by this case report-may also occur in the setting of NEC. An abdominal radiograph showed an isolated gastric pneumatosis, which is an unusual location of NEC. It is speculated that air moved through the connecting veins to the right atrium, the pneumatosis located in the gastric wall being a prerequisite to this pathophysiology. CONCLUSION The suspected NEC was located in the stomach enabling the intramural air to pass through connecting veins to the right atrium. The first specific sign of NEC in our case was air bubbles in the right atrium on echocardiography.
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Affiliation(s)
- Béatrice Müller
- Department of Intensive Care and Neonatology, University Children's Hospital, Zurich, Switzerland,
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23
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Taşkınlar H, Gündoğdu G, Celik Y, Avlan D, Naycı A. Challenging diagnosis between intussusception and necrotizing enterocolitis in premature infants. Pediatr Int 2014; 56:e1-3. [PMID: 24894937 DOI: 10.1111/ped.12311] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 01/08/2014] [Accepted: 01/21/2014] [Indexed: 11/28/2022]
Abstract
Although necrotizing enterocolitis (NEC) is a frequently encountered entity in premature infants in the neonatal intensive care unit, intussusception is extremely rare. Abdominal distension, bilious/non-bilious gastric residuals and bloody stool are the common clinical findings of both entities. Here we present three cases of intussusception misdiagnosed as NEC, two of which were complicated with intestinal perforation. Similar clinical findings of NEC and intussusception leads to misdiagnosis and delay in treatment, particularly in premature infants with intussusception.
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Affiliation(s)
- Hakan Taşkınlar
- Department of Pediatric Surgery, School of Medicine, Mersin University, Mersin, Turkey
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24
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Lai S, Yu W, Wallace L, Sigalet D. Intestinal muscularis propria increases in thickness with corrected gestational age and is focally attenuated in patients with isolated intestinal perforations. J Pediatr Surg 2014; 49:114-9. [PMID: 24439593 DOI: 10.1016/j.jpedsurg.2013.09.045] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Accepted: 09/30/2013] [Indexed: 11/16/2022]
Abstract
PURPOSE Intestinal perforations are common in premature infants, leading to a diagnostic dilemma between necrotizing enterocolitis and isolated intestinal perforation (IIP). IIP is thought to result from a congenital or acquired absence of the muscularis propria. However, developmental events leading to IIP are not well understood. This study examines the relationship between corrected gestational age (CGA) and intestinal muscle development in controls and patients with IIP. METHODS Specimens from stillbirths and infants undergoing intestinal surgery from 8 to 48weeks' CGA were collected from 2005 to 2012. Twelve patients with IIP were identified. Control specimens were collected during 25 fetal autopsies and 39 bowel resections. In each case, three sections of intestine were examined histologically for muscularis mucosa, circular and longitudinal muscle thickness. Comparisons of control and perforated specimens were performed via linear regression and ANOVA. RESULTS Controls and adjacent normal segments in IIP showed a linear relationship between thickness of circular and longitudinal muscles with CGA. Circular and longitudinal muscles were thinner in perforated segments than in adjacent normals and CGA-matched controls (p<0.05). CONCLUSION Intestinal muscularis propria increases in thickness with CGA. Muscle thickness is focally attenuated in patients with isolated intestinal perforations, while the remaining intestine is normal, suggesting that primary repair is an appropriate treatment.
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Affiliation(s)
- Sarah Lai
- Division of Pediatic Surgery, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Weiming Yu
- Department of Pathology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Laurie Wallace
- Division of Pediatic Surgery, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - David Sigalet
- Division of Pediatic Surgery, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.
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25
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Ahle M, Drott P, Andersson RE. Epidemiology and trends of necrotizing enterocolitis in Sweden: 1987-2009. Pediatrics 2013; 132:e443-51. [PMID: 23821702 DOI: 10.1542/peds.2012-3847] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE To investigate temporal, seasonal, and geographic variations in the incidence of necrotizing enterocolitis (NEC) and its relation to early infant survival in the Swedish population and in subgroups based on gestational age, birth weight, and gender. METHODS In the Swedish birth cohort of 1987 through 2009 all children with a diagnosis of NEC were identified in the National Patient Register, the Swedish Medical Birth Register, and the National Cause of Death Register. NEC incidence, early mortality, and seasonality were analyzed with descriptive statistics, Poisson regression, and auto regression. RESULTS The overall incidence of NEC was 3.4 in 10,000 live births, higher in boys than in girls (incidence rate ratio 1.22, 95% confidence interval 1.06-1.40, P = .005), with a peak in November and a trough in May, and increased with an average of ~5% a year during the study period. In most subgroups, except the most immature, an initial decrease was followed by a steady increase. Seven-day mortality decreased strongly in all subgroups over the entire study period (annual incidence rate ratio 0.96, 95% confidence interval 0.95-0.96, P < .001). This was especially marked in the most premature and low birth weight infants. CONCLUSIONS After an initial decrease, the incidence of NEC has increased in Sweden during the last decades. An association with the concurrent dramatically improved early survival seems likely.
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Affiliation(s)
- Margareta Ahle
- Department of Radiology, University Hospital, 581 85 Linköping, Sweden.
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Lampkin SJ, Turner AM, Lakshminrusimha S, Mathew B, Brown J, Fominaya CE, Johnson KK. Association between caffeine citrate exposure and necrotizing enterocolitis in preterm infants. Am J Health Syst Pharm 2013; 70:603-8. [DOI: 10.2146/ajhp120457] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Stacie J. Lampkin
- Department of Pharmacy Practice, School of Pharmacy, D’Youville College, Buffalo, NY
| | | | - Satyan Lakshminrusimha
- School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (SUNY), and Chief, Division of Neonatology, WCHB
| | - Bobby Mathew
- School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, and Division of Neonatology, WCHB
| | - Jack Brown
- Medicine and Public Health, University at Buffalo, SUNY, Research Assistant Professor, School of Medicine, University of Rochester, Rochester, NY, and Infectious Disease Specialist, University of Rochester Medical Center
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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; 48:562-7. [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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28
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Fox TP, Godavitarne C. What really causes necrotising enterocolitis? ISRN GASTROENTEROLOGY 2012; 2012:628317. [PMID: 23316377 PMCID: PMC3534306 DOI: 10.5402/2012/628317] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Accepted: 11/19/2012] [Indexed: 11/23/2022]
Abstract
Background. One of the most serious gastrointestinal disorders occurring in neonates is necrotising enterocolitis (NEC). It is recognised as the most common intra-abdominal emergency and is the leading cause of short bowel syndrome. With extremely high mortality and morbidity, this enigmatic disease remains a challenge for neonatologists around the world as its definite aetiology has yet to be determined. As current medical knowledge stands, there is no single well-defined cause of NEC. Instead, there are nearly 20 risk factors that are proposed to increase the likelihood of developing NEC. Aims and Objectives. The aim of this project was to conduct a comprehensive literature review around the 20 or so well-documented and less well-documented risk factors for necrotising enterocolitis. Materials and Methods. Searches of the Medline, Embase, and Science direct databases were conducted using the words "necrotising enterocolitis + the risk factor in question" for example, "necrotising enterocolitis + dehydration." Search results were ordered by relevance with bias given to more recent publications. Conclusion. This literature review has demonstrated the complexity of necrotising enterocolitis and emphasised the likely multifactorial aetiology. Further research is needed to investigate the extent to which each risk factor is implicated in necrotising enterocolitis.
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Peitz GJ, Hoie EB, Hoy S, Anderson-Berry A. Repeated bowel perforations with Ibuprofen lysine: a case report. J Pediatr Pharmacol Ther 2012; 13:166-9. [PMID: 23055878 DOI: 10.5863/1551-6776-13.3.166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Non-steroidal anti-inflammatory drugs (NSAID) have been used to close the patent ductus arteriosus in neonates for over two decades. Ibuprofen lysine, a parenteral NSAID, is labeled for the treatment of patent ductus arteriosus in neonates who do not respond to conventional medical management. While sharing many of the same adverse effects as indomethacin, spontaneous bowel perforation has not been reported. We describe a premature infant that experienced isolated bowel perforations after treatment with ibuprofen lysine for symptomatic patent ductus arteriosus.
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Chirinian N, Uji A, Isayama T, Shah V. Neonatal care in a Japanese NICU: notes based on a site visit. Neonatal Netw 2012; 31:89-96. [PMID: 22397793 DOI: 10.1891/0730-0832.31.2.89] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This article presents an overview of a neonatal intensive care unit along with resuscitative care and management of the 22 to 23 weeks gestational age infant is as it was noted during a visit to the NICU of a large academic center in Japan. Non-English speaking neonatology communities may be at a disadvantage of having their research and practices well known in the English speaking ones. Thus, visits such as this are beneficial in exchanging ideas and practices that may ultimately be mutually beneficial in reducing mortality and morbidity in a specific category of neonates.
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Abstract
Although ongoing patency of the ductus arteriosus is common in small extremely preterm infants, consensus is lacking regarding its clinical significance and treatment strategies. Literature regarding likelihood of spontaneous closure, impact on neonatal morbidity and long-term outcomes, and adverse effects of intervention has led to uncertainty as to the best course of action. Enhancing the determination of hemodynamic significance and refining patient selection for therapeutic intervention will streamline the decision-making process. Targeted neonatal echocardiography performed by the clinician has gained popularity worldwide, and preliminary data show that it has the potential to optimize patient outcomes. We review the arguments for and against medical and surgical therapy, explore how targeted neonatal echocardiography used in conjunction with biomarkers may refine the treatment approach, and consider future directions in the field.
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Affiliation(s)
- Arvind Sehgal
- Monash Newborn, Monash Medical Centre, Clayton, Victoria, Australia
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Ezaki S, Itoh K, Kunikata T, Suzuki K, Sobajima H, Tamura M. Prophylactic probiotics reduce cow's milk protein intolerance in neonates after small intestine surgery and antibiotic treatment presenting symptoms that mimics postoperative infection. Allergol Int 2012; 61:107-13. [PMID: 22377523 DOI: 10.2332/allergolint.11-oa-0305] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 07/13/2011] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND To examine occurrence of cow's milk protein intolerance (CMPI) in newborns that underwent small intestine surgery and the clinical profiles of those newborns with postoperative CMPI, and to evaluate the preventive effects of probiotics on CMPI. METHODS We retrospectively reviewed from 2000 to 2009, a total of 30 newborns required surgery on their small intestines. All of these patients had received antibiotics to prevent postoperative infection. Since 2005 we adopted a protocol of targeted probiotic therapy prophylaxis. RESULTS Eighteen patients received probiotic therapy, while twelve did not. One infant among those eighteen patients and eight patients among those twelve developed CMPI, a significantly lower rate for the group with probiotic therapy than that without it (p < 0.001). Patients with positive cultures for gram positive and gram negative organisms increased in number before and after surgery but then decreased after probiotics treatment. Poor weight gain, gastrointestinal symptoms, and rise in C reactive protein (CRP) levels were observed in all of those nine CMPI patients. Specific IgE antibodies were elevated in four of the nine subjects, and total IgE levels were elevated in seven of them. All CMPI patients had increased level of CRP without proven infections. CONCLUSIONS CMPI was induced in newborns after surgery on their small intestines and antibiotics treatment with presentation of symptoms that mimic postoperative infection. Development of CMPI in this population possibly involves disruption of intestinal flora. Administration of probiotics can reduce the incidence of CMPI after small intestine surgery. The elevated CRP level may be useful in the diagnosis of CMPI.
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Affiliation(s)
- Shoichi Ezaki
- Division of Neonatal Medicine, Center for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan. s_ezaki@saitama−med.ac.jp
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Genzel-Boroviczeny O. Leitlinie zur nekrotisierenden Enterokolitis (NEK). Monatsschr Kinderheilkd 2011. [DOI: 10.1007/s00112-011-2412-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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[Focal spontaneous colic perforation in term or near-term neonates: rare and potentially insidious]. Arch Pediatr 2011; 18:408-12. [PMID: 21397469 DOI: 10.1016/j.arcped.2011.01.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2010] [Revised: 10/06/2010] [Accepted: 01/08/2011] [Indexed: 11/20/2022]
Abstract
Two cases of neonatal focal spontaneous colic perforations are reported. The 1st infant, born at 36 3/7 weeks gestational age, presented on day 3 with crying, abdominal distension, and liquid stools. Clinical examination showed a slightly irritable hypothermic (35.7 °C) infant with a distended abdomen and few bowel sounds. Blood tests were normal apart from an elevated C-reactive protein level (59 mg/l). The abdomen x-ray was erroneously considered normal. The infant's condition remained stable for nearly 3 days. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was started on antibiotics and operated. Macroscopically, the entire gut was normal apart from a focal sigmoid perforation, which was stitched. A transmural colic biopsy revealed focal vascular dilation but was negative for necrotising enterocolitis or Hirschsprung disease. The infant recovered quickly. She is now a healthy, normal 3-year-old. The 2nd infant, born at 38 5/7 weeks gestational age, presented between day 1 and 2 with clinical signs of infection associated with slowly progressive ileus. The chest and abdomen x-ray was mistakenly considered normal. Frank septicemia developed. After reviewing the initial x-ray, pneumoperitoneum was suspected and confirmed by a cross-table lateral abdominal x-ray. The infant was operated. Macroscopically, the small intestine was normal, the ascending and transverse colons were dilated, and the descending and sigmoid colons were narrow. Three cecal perforations were discovered and stitched. An ileostomy and multiple colic biopsies were also performed. The postoperative course was complicated by persistent septic ileus due to descending and sigmoid colon leaks, which led to colic resections with end-to-end anastomosis. Rectal aspiration biopsies were also performed. At 1 month of age, the infant was discharged from the hospital. The ileostomy was closed in two steps at 2 and 5 months of age. A normal sweat test excluded cystic fibrosis. All colic and rectal biopsies revealed nonspecific inflammatory signs and excluded necrotizing enterocolitis and Hirschsprung disease. Nonspecific irregular thinning of muscularis mucosae and muscularis propria were observed in the two resected colic segments. The boy is now a healthy 7-year-old. The incidence of neonatal focal spontaneous colic perforations at term or close to term is unknown but probably very rare. Our department is the neonatal referral center for approximately 14,000 annual births. In the last 10 years (2000-2009), out of 5115 neonatal admissions in our unit, only ten cases have presented a neonatal spontaneous intestinal perforation, seven of ten in very-low-birth-weight infants and three of ten in term or near-term neonates (one with Hirschsprung disease and the two cases reported herein). In the same period, 108 infants suffered from necrotizing enterocolitis, seven of 108 were term infants and 6 out of 7 had a congenital heart disease. The medical literature is poor on the subject of focal spontaneous colic perforations at term; no risk factor is described. The most specific clinical sign seems to be the abdominal distension. The presence of pneumoperitoneum on an abdominal x-ray is the most sensitive paraclinical sign. In case of an intestinal perforation, surgery must be performed quickly. The vital prognosis seems to be good. The objective of this study was to draw pediatricians' attention to focal spontaneous colic perforations in term or close to term newborns. In the cases reported, the diagnostic delays could have been prevented if the entity - with its radiological manifestation - had been well known.
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Sharma R, Hudak ML, Tepas JJ, Wludyka PS, Teng RJ, Hastings LK, Renfro WH, Marvin WJ. Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis. J Perinatol 2010; 30:786-93. [PMID: 20410905 DOI: 10.1038/jp.2010.59] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To examine the role of indomethacin in neonatal gut injury. STUDY DESIGN Infants born at gestational age 23 weeks and with birth weights 400-1200 g were included in this prospective prevalence study of neonatal gut injury. Infants with isolated intestinal perforation (IIP) confirmed at laparotomy or at autopsy or with necrotizing enterocolitis (NEC) were identified. Data were abstracted bi-weekly. RESULT Among 992 study infants, 58 infants exposed solely to prenatal indomethacin did not show an increased rate of neonatal gut injury. Any postnatal indomethacin exposure (n=611) increased the odds of IIP (OR 4.17, CI, 1.24-14.08, P=0.02) but decreased the odds of NEC (OR 0.65, CI 0.43-0.97, P=0.04). There was a negative association between the timing of indomethacin-exposure and the odds of developing IIP (OR 0.30, CI 0.11-0.83, P=0.02). Compared with NEC, IIP occurred at an earlier age (P<0.05) and was more common (P<0.05) among infants who received early indomethacin (first dose at <12 h of age) to prevent intraventricular hemorrhage than among infants who were treated with late indomethacin for closure of a patent ductus arteriosus (PDA). Unlike the classic hemorrhagic ischemic lesions of NEC in which large areas of tissue were inflamed or necrotic, the IIP lesions were small and discrete. CONCLUSION Early (<12 h) postnatal indomethacin exposure was associated with an increased odds of IIP in very low birth weight infants whereas its later use for closure of a PDA appeared to provide protection against NEC. The paradoxical effect of the timing of indomethacin on IIP versus on NEC may be related to the different pathogeneses of the two diseases. Our findings also suggest that PDA may contribute to NEC.
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Affiliation(s)
- R Sharma
- Division of Neonatology, Department of Pediatrics, University of Florida College of Medicine at Jacksonville, 655 West 8th Street, Jacksonville, FL 32209-6511, USA.
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Dane B, Dane C, Aksoy F, Cetin A, Yayla M. Antenatal Bartter syndrome: analysis of two cases with placental findings. Fetal Pediatr Pathol 2010; 29:121-6. [PMID: 20450264 DOI: 10.3109/15513811003777276] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The prenatal diagnosis of Bartter syndrome can be based on the high chloride level in the amniotic fluid. Microscopic examination of the placenta in untreated cases showed extensive mineralization in the chorionic villi in previous studies. Two cases were presented at 26-29 weeks of gestation with severe polyhydramnios. The mothers were treated with Indomethacin, KCl, and serial amniocentesis in order to reduce the amniotic fluid volume and prevent fetal hypokalemia. The microscopic examination of the placenta revealed focal calcification and acute atherosis in placental vessels. The treatment with Indomethacin in the antenatal period can prevent severe nephrocalcinosis.
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Affiliation(s)
- Banu Dane
- Department of Gynecology & Obstetrics, Haseki Training & Research Hospital, Istanbul, Turkey
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Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep. PLoS One 2009; 4:e5837. [PMID: 19503810 PMCID: PMC2688751 DOI: 10.1371/journal.pone.0005837] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2009] [Accepted: 05/12/2009] [Indexed: 11/19/2022] Open
Abstract
Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis. Chorioamnionitis was induced at different gestational ages (GA). Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d) inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO) donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase. Our results indicate that the distribution of the tight junctional protein ZO-1, the immune defence and vascular function are immature at low GA and are further compromised by endotoxin-induced chorioamnionitis. This study suggests that both prematurity and inflammation in utero disturb fetal gut development, potentially predisposing to postnatal intestinal pathology.
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Spontaneous Intestinal Perforation. POLISH JOURNAL OF SURGERY 2009. [DOI: 10.2478/v10035-009-0012-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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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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