Via Research Recognition Day Program VCOM-Carolinas 2025

Case Reports

UNUSUAL PRESENTATION OF NECROTIZING ENTEROCOLITIS IN A TERM INFANT Erin McCoy OMS-III 1 ; Sonia Vanegas OMS-IV 1 ; Jaime Brown MD 2 ; Hanna S Sahhar MD, FAAP, FACOP 1,2

1 Edward Via College of Osteopathic Medicine, Carolinas Campus, Department of Pediatrics, Spartanburg, SC 2 Spartanburg Regional Healthcare System, Department of Pediatrics, Pediatric Intensive Care Unit, Spartanburg, SC

Introduction

Case Presentation

Discussion

References According to the literature, NEC occurs more commonly in preterm infants but is relatively rare in term infants, accounting for about 10% of cases. It can be speculated that term infants are less susceptible to NEC due to a more mature intestinal barrier. However, when NEC is present in this population, it often involves different predisposing factors. This case highlights NEC in a term infant with concurrent C. difficile colonization and a history of sepsis, providing insights into the complex interplay of microbial disruption, systemic factors, and NEC pathogenesis. Unlike preterm infants, whose risk factors for NEC include immaturity of the intestinal barrier, hypoxic-ischemic injury, and early formula feeding, term infants typically have different risk factors such as intrauterine growth retardation (IUGR), birth asphyxia, congenital heart disease, gastroschisis, polycythemia, hypoglycemia, sepsis, exchange transfusion, umbilical lines, milk allergy, premature rupture of membranes with or without chorioamnionitis, and gestational diabetes. 6 Sepsis, in particular, is an important predisposing factor for NEC during the neonatal period as it can disrupt intestinal perfusion and alter the gut microbiome. In this case, the patient was treated with ampicillin and gentamicin for 36 hours during her NICU stay for sepsis, which may have contributed to a disruption of the intestinal environment, increasing susceptibility to NEC. The disruption of normal intestinal flora (dysbiosis) is a well known feature in NEC pathophysiology, characterized by the overgrowth of pathogenic bacteria and a reduction in protective bacteria. In this context, the patient’s prior sepsis rule out and antibiotic exposure may have played a role in setting the stage for NEC development. The detection of C. difficile DNA amplification in this case, while toxin-negative, may indicate microbial imbalance rather than direct pathogenicity as toxin-producing strains are typically associated with active disease, not toxin-negative ones 7 . This case shows the importance of having a broad differential diagnosis when a young infant presents with bloody stools and accounting for all previous exposure to antibiotics. A thorough workup, including stool studies and imaging, was critical in identifying NEC in this patient. Furthermore, this case shows the potential contribution of microbial dysbiosis in the pathogenesis of NEC in term infants, with C. difficile colonization possibly serving as a marker of an altered gut environment rather than a direct causative agent. Although C. difficile colonization is common in neonates, its detection in NEC cases can point out the important question about the role of gut microbiota and systemic risk factors. This case demonstrates the need for further research into the interactions between microbial dysbiosis, systemic stressors like sepsis, and NEC pathogenesis, particularly in term infants. Understanding the relationship could help in creating strategies for prevention and management, such as targeted microbial therapies or approaches to maintain intestinal homeostasis in at risk populations. 1. Fiona Wertheimer, Roxanne Arcinue, Victoria Niklas; Necrotizing Enterocolitis: Enhancing Awareness for the General Practitioner. Pediatr Rev October 2019; 40 (10): 517 – 527. https://doi.org/10.1542/pir.2017-0338 2. Renu Sharma, Mark Lawrence Hudak,A Clinical Perspective of Necrotizing Enterocolitis: Past, Present, and Future, Clinics in Perinatology, Volume 40, Issue 1, 2013, Pages 27-51,ISSN 0095-5108,ISBN 9781455771363, https://doi.org/10.1016/j.clp.2012.12.012. 3. Rose AT, Patel RM. A critical analysis of risk factors for necrotizing enterocolitis. Semin Fetal Neonatal Med. 2018 Dec;23(6):374-379. doi: 10.1016/j.siny.2018.07.005. Epub 2018 Aug 1. PMID: 30115546; PMCID: PMC6269219. 4. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011 Jan 20;364(3):255-64. doi: 10.1056/NEJMra1005408. PMID: 21247316; PMCID: PMC3628622. 5. Barrie S. Rich, Stephen E. Dolgin; Necrotizing Enterocolitis. Pediatr Rev December 2017; 38 (12): 552 – 559. https://doi.org/10.1542/pir.2017-0002 6. Maayan-Metzger A, Itzchak A, Mazkereth R, Kuint J. Necrotizing enterocolitis in full-term infants: case-control study and review of the literature. J Perinatol. 2004 Aug;24(8):494-9. doi: 10.1038/sj.jp.7211135. PMID: 15229620; PMCID: PMC7099291. 7. Anatoly Grishin, Stephanie Papillon, Brandon Bell, Jin Wang, Henri R. Ford, The role of the intestinal microbiota in the pathogenesis of necrotizing enterocolitis, Seminars in Pediatric Surgery, Volume 22, Issue 2, 2013, Pages 69-75, ISSN 1055-8586, https://doi.org/10.1053/j.sempedsurg.2013.01.002. 8. Sarah A. Coggins, James L. Wynn, Jörn-Hendrik Weitkamp, Infectious Causes of Necrotizing Enterocolitis, Clinics in Perinatology, Volume 42, Issue 1, 2015, Pages 133-154, ISSN 0095-5108, ISBN 9780323376372, https://doi.org/10.1016/j.clp.2014.10.012. No relevant financial affiliations or conflicts of interest. If the authors used any personal details or images of patients or research subjects, written permission or consent from the parent (or legal guardian) was obtained. This work was not supported by any outside funding. The authors would like to acknowledge and thank Dr. Imelda Uy, neonatologist for assisting in the care this patient and providing a valuable insight on the condition. Acknowledgements

Necrotizing Enterocolitis is an inflammatory condition of the bowel causing the most common surgical emergency in the newborn. 1 Most commonly seen in premature infants with only 7% to 15% of all NEC cases happening in term or late preterm infants2, other risk factors for development of necrotizing enterocolitis include formula feeding, sepsis, empiric antibiotics, maternal infection, and acid suppression. 3 The pathophysiology of necrotizing enterocolitis is significantly debated. It is suggested that increased inflammation occurs due to a combination of genetics, intestinal immaturity, abnormal microbial colonization, although no specific microbial species has been isolated, 2 and a reactive intestinal mucosa. 4 Typically, patients with necrotizing enterocolitis present with bloody bowel movements and abdominal distension that may be accompanied by symptoms similar to sepsis such as temperature instability, hypotension, and labs indicating metabolic acidosis. 5 Commonly, bacterial stool cultures return positive for Escherichia coli, clostridium perfringens, and klebsiella. 5,6 The diagnosis of Necrotizing Enterocolitis is confirmed via abdominal radiographs visualizing pneumatosis intestinalis and a bubbly appearance with thick walled stacked bowel loops. 1 Initial treatment includes withholding enteral feeds and broad spectrum antibiotics. 5 With utilization of the Bell’s Criteria1 for staging, surgical exploratory laparotomy is completed with removal of necrotic bowel 5 when pneumoperitoneum occurs. Our 2 weeks old female patient was born full term at 7lbs 10.2 oz. During her initial hospitalization she was transferred to the NICU for late onset apnea and tachypnea. At the time, sepsis versus withdrawal of maternal SSRI constituted the main differential. In the NICU, she responded to supplemental oxygen therapy and a combination of ampicillin and gentamicin given through a peripheral line for 36 hours. Her symptoms resolved and she was discharged. At two weeks of life, the infant presented to the Emergency Department due to blood found in her stool. Her parents reported the infant had been taking her regular 4 oz feeds every 3 hours of Similac. They reported they had not changed her formula since birth. The only positive on review of systems was recent sneezing. Patient’s vitals were unremarkable in the ED with physical exam showing a soft non distended abdomen with active bowel sounds in all four quadrants. Relevant laboratory results include hemoglobin 15.4 g/dL (NR: 12 - 20 g/dL), platelets 448 x10 9 /L (NR: 150 x10 9 /L – 450 x10 9 /L), bicarbonate 22.3 mEq/L (NR: 16 mEq/L – 24 mEq/L), and C-reactive protein 2 mg/L (NR: <10 mg/L). Stool Studies were significant for occult blood and lactoferrin. Initial abdominal Xray showed possible intramural air in the ascending colon raising concern for pneumatosis (Figure 1). A preliminary diagnosis of necrotizing enterocolitis was made. The patient was admitted and started on vancomycin, cefepime, and metronidazole with serial abdominal X-rays every 6 hours. Surgery was consulted in case escalation of care was needed. Case Presentation

Figure 1. Inital X-Ray of the Abdomen showing possible intramural air in the ascending colon raising concern for pneumatosis.

The following morning, C DIFF DNA Amplification returned positive with a negative C difficile toxin antigen. All other bacterial stool toxins including salmonella and shigella were negative. Repeat X-Ray showed bubbly air pattern within the splenic flexure, more pronounced than comparison exam (Figure 2). The patient was transferred to the PICU and placed on TPN and lipids for bowel rest. Vancomycin was discontinued per recommendation of pharmacist due to the lack of toxin production.

Figure 2. Repeat X-Ray showing bubbly pattern within the splenic flexure and descending colon that is more pronounced than the comparison exam.

Over the next 6 days, X-Rays were repeated daily, and the abdomen remained soft and nondistended. Results on the X-rays slowly improved, until day 8, where the X-Ray showed complete resolution of previously reported abnormalities (Figure 3). The patient tolerated advancing diet to Alimentum formula then lipids and TPN were discontinued. The Patient was discharged home with resolution of symptoms.

Figure 3. Final X-Ray showing normal intestines and resolution.

2025 Research Recognition Day

73