Introduction

Necrotising Enterocolitis (NEC) is one of the most serious gastrointestinal diseases that affects newborns, particularly those born prematurely and low-weight infants. The disease typically involves inflammation and necrosis of the intestinal tissue, which can lead to severe complications, including sepsis, intestinal perforation, and even death.¹ In Neonatal intensive care units (NICUs), NEC remains a significant cause of newborn morbidity and mortality despite decades of research.²

Causes and Risk Factors of Necrotising Enterocolitis

Although NEC is caused by multiple reasons, there is growing research indicating that early antibiotic exposure may significantly increase the risk of developing the disease.³  NEC is a spectrum of gastrointestinal illnesses with overlapping features rather than a single, homogeneous condition. Classic NEC is the most prevalent and extensively researched type, mostly affecting premature babies, particularly those born before 32 weeks of gestation.^1,4

It usually appears when enteral feeding begins, when the young gut is first exposed to nutritional substrates and microbial colonisation. 

Other forms include: 

• Transfusion-associated NEC, a type that develops after transfusions of packed red blood cells. Preterm newborns with chronic anaemia are especially susceptible due to intestinal hypoxia-reperfusion injury during transfusion
• Solitary NEC, which occurs in full-term infants, is often linked with perinatal hypoxia or congenital heart disease.^6,7,8

Role of Antibiotics in NEC Development

As a preventative or empirical approach for managing suspected sepsis, antibiotics are typically given to premature infants. Antibiotics can save lives when used to treat established illnesses, but prolonged or unnecessary use has been associated with adverse effects on the neonatal gut microbiome.^1,10 A diverse microbiome is crucial for intestinal development, immune system growth, and maintaining barrier function. Early antibiotic exposure disrupts the balance, leading to dysbiosis — a condition characterised by an overgrowth of harmful bacteria and a reduction in microbial diversity. These disruptions are central to NEC pathogenesis.^9,10,11,12

Classification of NEC

An increased incidence of NEC has been associated with the prolonged use of antibiotics during the first few days of life, according to several observational studies. Studies show that preterm infants receiving extended therapy beyond 48-72 hours have incidence of NEC than those given shorter courses or none at all.^13,14 Preterm newborns with chronic anaemia are especially susceptible to this type, which is thought to involve intestinal hypoxia-reperfusion injury during transfusion. Another unique form of NEC is term or solitary NEC, which occurs in full-term infants frequently with underlying disorders, including perinatal hypoxia or congenital heart disease. Hypoxia-ischemia is believed to be more significant in these situations than microbial imbalance. 

Clinical Presentation and Classification of NEC

The severity of NEC can be divided into two categories:

• Medical NEC, managed with bowel rests, antibiotics and supportive care^13,14
• Surgical NEC, requiring laparotomy or drainage due to perforation or severe necrosis

Surgical NEC carries higher mortality, making prevention and early detection crucial.^13,14

Management and Treatment Approaches

In cases of intestinal perforation, peritonitis, or severe necrosis, surgery becomes necessary. The standard approach is laparotomy with restriction of necrotic bowel, although peritoneal drainage may be used in critical neonates. Surgical NEC survivors often face long-term complications such as intestinal strictures, short bowel syndrome, and feeding issues. Even with treatment, infants may require extended hospitalisation and face growth and neurodevelopmental delays. Long-term follow-up involves developmental checks, nutritional support, and surgical monitoring.^1,15

Prevention Strategies

The best method for minimising the occurrence of NEC is still prevention. 

• Antibiotic stewardship, limiting empirical treatment to cases with a strong suspicion of sepsis and discontinuing immediately if cultures are negative¹⁶
• Human milk feeding, which provides protective bioactive factors that promote healthy colonisation¹⁷
• Probiotics, specifically probiotic strains, help reduce the risk of NEC by supporting gut colonisation with beneficial bacteria, restoring microbiome balance, and strengthening intestinal barrier function¹⁶
• Standardised feeding regimens, structured introduction of feeds in NICUs, are linked to lower NEC rates¹⁷

Conclusion

In conclusion, despite a high rate of morbidity and mortality, NEC remains one of the most recognised complications in neonatal critical care. While NEC pathophysiology is complex, prolonged and inappropriate antibiotic use is a key modifiable risk factor. Disruption of the microbiota weakens immune regulation and intestinal integrity, increasing vulnerability. Prevention requires balanced antibiotic use, breast milk prioritisation, and structured feeding. The challenge lies in balancing the life-saving role of antibiotics with their potential harm to neonatal gut health.

Summary

Necrotising enterocolitis (NEC) is one of the most serious gastrointestinal emergencies in neonatology. It primarily affects premature and very low birth weight infants. The condition arises from a combination of immature gut immunity, microbial imbalance, and uncontrolled inflammatory responses. Increasing evidence suggests that early and prolonged antibiotic exposure is a key modifiable risk factor. Broad-spectrum antibiotics, particularly third-generation cephalosporins and carbapenems, are strongly associated with the development of NEC. These drugs disrupt the neonatal gut microbiome, delay colonisation by beneficial species, and promote the growth of pathogenic bacteria. The resulting dysbiosis weakens the intestinal barrier, triggering inflammatory cascades that lead to mucosal injury and necrosis.

Antibiotics remain essential for preventing and treating neonatal sepsis, but their misuse or unnecessary use can heighten the risk of NEC. Preventive strategies include careful antibiotic stewardship, prioritising human milk feeding, using standardised feeding protocols, and considering probiotics in selected cases. For infants who develop NEC, early recognition and management are critical, ranging from bowel rest and targeted antibiotics to surgical treatment in severe cases. Optimising antibiotic practices and supporting the healthy development of the gut microbiome may help reduce the incidence and severity of NEC in high-risk infants.