Prenatal theophylline and necrotizing enterocolitis in premature newborn infants

To determine whether prenatal theophylline therapy would increase the incidence of neonatal necrotizing enterocolitis (NEC) we studied bowel dysfunction in 59 consecutive premature infants (g.s. < 34 weeks), whose mothers were treated with theophylline as a tocolytic during the last trimester, or as surfactant synthesis inductor, for at least three days prior to premature labor (Group A). As case-control we considered the premature, matched for gestational age born immediately before, and whose was untreated with theophylline (Group B). NEC occurred in one patient from group A during the second postnatal week, and surgery was performed. First passage of meconium and start of enteral feeding were comparable in groups A and B, while gastric residuals lasting more than 4 days were found statistically increased (p < 0.03) in antenatally treated group A prematures. Furthermore, 18 out of 49 prematures postnatally treated with theophylline had gastric residuals (36%) with respect to 5 out of 69 untreated (7%) (p < 0.001). Also the premature infants treated ante and postnatally with theophylline showed a statistically significant increase of lasting gastric residuals with respect to the untreated, 13/16 vs 5/7, respectively (p < 0.03). Antenatal theophylline administered to high risk mothers, when maternal diseases do not allow the use of steroids, does not appear to later increase the risk of NEC in premature infants, and provides a chance to avoid the risks related to premature birth. Inhibitory activity on gut motility and gastric irritability are only detectable during the first postnatal days, enhanced by gut immaturity of preterm infants.