Role of melatonin for prevention of necrotizing enterocolitis in preterm infants: a randomized controlled trial

Feeding intolerance (FI) in preterm infants may signal necrotizing enterocolitis (NEC), in which oxidative stress (OS) plays a central role. Melatonin has demonstrated promise in mitigating neonatal OS-related diseases. The study is aimed to assess the effect of enteral melatonin on the progression of FI symptoms, NEC incidence, and tumor necrosis factor-alpha (TNF-α) levels in preterm neonates with FI, compared with conventional therapy (CT). Ninety preterm neonates with FI were randomly assigned to either the melatonin group (MT, n = 45), who received melatonin plus conventional therapy, or the conventional group (CT, n = 45), who received conventional treatment. Melatonin was administered enterally in two doses of 10 mg each, 1 h apart. TNF-α levels were measured in all patients 72 h posttreatment. CT group experienced extended hospital stay, longer feeding discontinuation, delayed full enteral intake, higher NEC incidence, increased mortality, and higher TNF-α compared with the MT group (P = .032, <.001, <.001, <.001, .03, and <.001, respectively). Enteral melatonin significantly reduced NEC incidence and mortality, accelerated achievement of full enteral feeding, and lowered TNF-α levels in preterm neonates with FI. It demonstrates a practical, affordable, orally administered therapy that is accessible and reproducible in low-resource settings, addressing the burden of NEC in preterm infants where it is critically needed.