Table 5.

Translational prospects and boundaries of NETs- directed or NET-adjacent strategies.

Strategy	Action node	Evidence status	Potential advantage	Key translational question
PAD4 inhibition	Histone citrullination/NET formation	Benefit in LPS-hypoxia NEC models; harm possible in high-translocation models	Direct blockade of a defined execution step	When is infection controlled enough to inhibit formation without losing mucosal defense?
DNase/extracellular DNA clearance	Deposited DNA scaffold	Improved outcomes in a mouse NEC model	Preserves formation while limiting persistence	Can DNA clearance be timed after bacteremia risk falls and before irreversible necrosis?
nNIF-like peptides	Terminal NET formation steps	Peritonitis/sepsis models; NEC-specific data lacking	Physiologically aligned with neonatal endogenous regulation	Does supplementation increase translocation in real NEC subtypes?
Platelet/GSDMD/IP6K1/TREM1 nodes	Immunothrombosis and inflammatory amplification	Emerging NEC mechanism studies	More selective than global neutrophil suppression	Which node is causal in which subtype and phase?
Microecological/barrier repair	Upstream triggers: dysbiosis, metabolites, epithelial injury	Human milk components, defined metabolites, fecal filtrate/virome studies	Prevention-aligned and potentially safer	Are NET burden and epithelial repair measured as intermediate outcomes?