Enteral theophylline and necrotizing enterocolitis in the low-birthweight infant

In a two-phased retrospective study, clinical factors associated with the development of necrotizing enterocolitis (NEC) in neonates were identified. The first phase found 13 infants with NEC who had been treated more frequently with enteral theophylline (P < .025) and fed higher volumes (> 150 mL/kg/day; P < .05) than controls of comparable birthweight and postnatal age. Seven of the 13 infants with NEC, weighing < 1,250 g at birth, had previously received intravenous aminophylline and been changed to enteral theophylline within six days before the onset of NEC. Prolonged rupture of membranes was more prevalent (P < .025) in infants with birthweight > 1,250 g who developed NEC in the first week of life. Maternal preeclampsia helped protect against the development of NEC (P < .05). In the second study phase, 59 infants with birthweights < 1,250 g were evaluated for gastrointestinal disturbance within five days of the introduction of any enteral medication. The frequencies of NEC, NEC scare, and feeding intolerance were greater in infants treated with enteral theophylline than in those treated with all other enteral medications combined (P < .05). This two-phased study confirms the multifactorial etiology of NEC and indicates that the administration of enteral theophylline to young infants < 1,250 g may be a predisposing factor to GI disturbances and NEC. These findings warrant a further prospective investigation.