Elevated Urinary Intestinal Fatty Acid Binding Protein Precedes Clinical Indicators of Necrotizing Enterocolitis

Introduction: Necrotizing enterocolitis (NEC) is usually diagnosed in premature infants after the development of feeding intolerance and characteristic physical and imaging findings including hematochezia, abdominal distension, and pneumatosis intestinalis. Earlier detection of a subclinical prodrome in NEC might allow for the institution of measures that could prevent or attenuate the severity of disease. Previously, we demonstrated that the urinary content of intestinal fatty acid binding protein (iFABP u), a sensitive and specific marker for intestinal mucosal injury, was elevated in the first 3 days of life (DOL) in 9 of 9 infants who subsequently developed NEC and 38% of those who did not. We hypothesized that iFABP u would also be elevated in infants beyond the first days of life, prior to their first clinical manifestation of NEC. Methods: Urine was collected daily from 62 infants of gestational age 24-28 weeks. Demographics, neonatal resuscitation, feeding history, and the incidence of sepsis were noted. Subjects were determined to have had Bell stage 2 or 3 NEC based upon clinical, imaging and operative findings. In all subjects with NEC and in 10 age-matched controls, iFABP u was determined using an ELISA. iFABPu>1000 pg/ml was considered elevated. Results: Six subjects developed NEC between DOL 11 and 36. In each of these infants, iFABPu was elevated, beyond DOL 4, to between 3700 and >10,000 pg/ml, at least 3 days prior to the first clinical indication of disease. Among control infants, 8 had a transient or sustained elevation in iFABPu beyond DOL 4. In 6, this was temporally associated with feeding intolerance and/or abdominal distension and dilated loops that led to cessation of feedings. Conclusions: In all infants with NEC, iFABPu was elevated at least 3 days prior to the first clinical indication of the disease. The duration of this subclinical, biochemical prodrome was great enough to suggest that iFABPu screening of premature infants might allow for timely institution of measures such as withholding of feedings, administration of antibiotics, or treatment with experimental agents such as epidermal growth factor, that could ameliorate or prevent NEC. Elevated iFABPu in control subjects was mostly associated with feeding intolerance that may, in some cases, have represented undiagnosed NEC. Therefore, iFABPu was a very sensitive and specific indicator of significant intestinal compromise, whether or not it was clinically apparent. The potential for iFABPu monitoring to reduce the incidence of NEC will be assessed in a prospective trial in which iFABPu findings will be communicated to neonatologists in real-time and will contribute to management decisions. (Figure presented).