Table 1.
Experimental details, strengths, and limitations of models of NEC in rats
| Experimental Details | Strengths | Limitations | References |
|---|---|---|---|
| Formula feeding and hypoxia (newborn rats). | Utilizes known clinical risk factors. | Rats may be exposed to maternal breast milk before induction of the model. | 7 |
| Formula feeding, hypoxia and hypothermia (newborn rats). | Utilizes known clinical risk factors. | Rats may be exposed to maternal breast milk before induction of the model. | 6 |
| High disease severity. | |||
| Formula feeding, hypoxia and hypothermia (premature rats). | No maternal milk exposure. | Cesarean section is required. | 14, 15, 28, 29, 47, 48, 53, 58, 59 |
| Intestinal barrier is immature. | In patients, NEC does not develop immediately after birth questioning the clinical relevance. | ||
| Formula-feeding, hypoxia and hypothermia with the addition of commensal bacteria from adult rats (premature rats). | Includes risk factors associated with bacterial colonization. | The bacterial components that are added may not be representative of the clinical situation. | 13, 14, 25, 37, 66, 88 |
| High disease severity. | |||
| Formula-feeding, hypoxia and hypothermia with the addition of intragastric LPS. | The introduction of bacterial component (i.e., LPS). | LPS is not representative of all bacterial components relevant to NEC. | 21, 32, 38 |
| Formula-feeding, hypoxia, hypothermia reoxygenation (100% O2 for 5 min). | Increased intestinal injury. | The delivery of 100% oxygen to premature infants is avoided given known toxicity. | 62 |
| Formula-feeding and hypoxia, reoxygenation (5% oxygen for 3 to 10 min), no hypothermia. | Avoidance of hypothermia simplifies the model. | Clinical relevance is uncertain given the prolonged reoxygenation. | 19 |
| Formula-feeding and hypoxia, addition of Cronobacter sakazakii. | Allows for the direct investigation of the role of Cronobacter sakazakii, which is associated with NEC. | Cronobacter sakazakii causes a minority of NEC cases in patients, and is more likely to be associated with other infections (i.e., meningitis). | 52 |
| Ischemia and reperfusion of the intestine in older rats. | More accurately is an oxidative stress model. | Performed in older animals when the intestine is more mature; relevance to clinical NEC is uncertain. | 50, 80 |
NEC, necrotizing enterocolitis.