Berseth, Carol Lynn

SummaryPrevious studies have shown that orally administered epidermal growth factor (EGF) enhances neonatal intestinal growth and that it may be absorbed in the intestine and bound by other organs. This study investigated whether the ingestion of EGF would be associated with growth of nonintestinal organs. In short‐term studies, 87 newborn rat pups were fed artificial formula containing various concentrations of EGF for 39 h. In long‐term studies, suckling newborn pups were fed EGF or an equal volume of distilled water for 5 days. The pups fed formula containing EGF for 39 h had a significant increase in hepatic incorporation of [3H]thymidine into DNA compared with pups not fed EGF. By 5 days of age, 13 pups fed EGF had heavier livers that contained more DNA and RNA compared with 14 control pups. Moreover, EGF‐fed pups had heavier hearts and kidneys than pups fed no EGF. These data suggested that ingestion of EGF is associated with the growth of nonintestinal organs.

SummaryIn the fasting state, antral motor activity is similar in preterm and term infants, but the antral responses to feeding have not been compared in preterm and term infants. The purpose of this study was to use low‐compliance, continuous perfusion manometry to compare antral and duodenal feeding responses in 13 preterm and nine term infants within the first 14 days of life. Confirming our previous studies, fasting antral motor activity was similar in preterm and term infants, but duodenal activity differed. Individual duodenal cluster activity was of shorter duration in preterm than in term infants (p < 0.01). Motor activity in antrum and duodenum changed in both groups of infants in response to an intraduodenal milk infusion of 4 ml/kg/2 h; however, the nature of the change varied in the two regions. In term infants, the number of antral pressure waves, the duration of antral clusters, and the antral motility index decreased by one third or more during feeding when compared with fasting (all p < 0.05). In contrast to the decrease in antral activity in response to feeding, the duodenal motility index and cluster activity increased significantly during feeding compared with fasting (both p < 0.05). The divergent response of antral and duodenal motor activity in response to feedings was also seen in preterm infants. Antral pressure waves, the duration of antral clusters, and the antral motility index were decreased during feeding (all p < 0.005 or less). Conversely, the preterm duodenal motility index and the duration of cluster activity increased during feeding compared with fasting (p < 0.05 or more). The suppression of antral motor activity in response to feeding is dissimilar to that described in adults fed solids and may be nutrient related. Since these antral responses occurred in response to duodenal feedings, they may have been mediated by hormones or local reflexes that are intact as early as 26 weeks' gestation.

As an extension of an earlier study showing that manometry can identify preterm newborns at risk for feeding intolerance, the authors investigated whether abnormalities of intestinal motor activity underlie the feeding intolerance seen in asphyxiated newborns. Low-compliance perfusion manometry was recorded within the first postnatal week in 25 term neonates admitted consecutively for respiratory diseases. Eleven of these neonates were identified to have experienced birth asphyxia because three concurrent features were present: 1-minute Apgar score of less than 2; 5-minute Apgar score of less than 4; and recurrent seizures within the first 48 postnatal hours. The remaining 14 neonates, who did not have any of these three characteristics, were considered to be nonasphyxiated control neonates. Motor activity differed in nonasphyxiated and asphyxiated neonates during fasting and feeding. During fasting, asphyxiated neonates had less migrating activity than nonasphyxiated neonates. In addition, episodes of motor quiescence and clustered phasic activity were less well organized in asphyxiated neonates. Both groups of neonates displayed a change in motor activity in response to a feeding infusion; however, the response was initiated significantly sooner in asphyxiated than in control neonates. All of the 11 asphyxiated neonates were intolerant of enteral feedings during the first poststudy week, but no control neonate was feeding intolerant. Six of the asphyxiated neonates were reevaluated 1 to 2 weeks later. During this latter study, motor activity in these asphyxiated neonates was similar to that of nonasphyxiated neonates; 5 of 6 of these neonates subsequently tolerated enteral feedings. It is speculated that changes in motor activity underlie the feeding intolerance that asphyxiated neonates typically exhibit. Furthermore, manometrics may provide a direct method to monitor functional responsiveness of the intestinal tract to identify those neonates at risk for feeding intolerance and to guide feeding management in these neonates.

Controversy and public attention has swirled around the recent Jane Doe case and the recent "Baby Doe" Rule issued by Secretary of Human Services Margaret Heckler.1 Jane Doe was an infant born with congenital esophageal atresia and Down's syndrome. The child's parents and physician chose to defer surgical repair of the child's esophageal anomaly. The child's anomaly precluded provision of enteral nutrition. No parenteral nutrition was provided, and the child died 6 days later. Several months later, Secretary Heckler of the Department of Health and Human Services issued a directive stating that hospitals receiving federal funding must display on a sign a telephone number by which anonymous observers could report parents or physicians who were witholding medical treatment or food from defective newborns.

Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formula that contained 1.2, 3.0, and 6.0 micrograms/ml EGF for 39 h had greater incorporation of [3H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate in part, breast milk-enhanced neonatal intestinal growth.

Low-compliance perfusion manometry and clinical outcome were used to assess the chronic effects of feeding on functional maturation of the preterm intestine in 32 infants. During the first postnatal week, 16 infants received a small volume of formula to supplement their routine parenteral nutrition (24 ml.kg-1.day-1), and 16 received an equal volume of water. After 10 days of enteral "feedings," the manometric tracings of those infants who had received nutrient feedings had more migrating activity (P < 0.01) and less clustered phasic activity (P < 0.05) during fasting than did the tracings of those infants who had received nonnutrient feedings containing sterile water. Infants who received nutrient feedings demonstrated a change in motor activity in response to feeding; infants who had received water feedings failed to show a change in motor activity in response to feeding. After water-fed infants were given formula feedings for 2 wk, their motor activity patterns were similar to those who had initially been fed formula, and their motor responses to feeding were restored. Despite normalization of their motor activity patterns by 1 mo of age, these water-fed infants established full enteral nutrition and full nipple feedings later than did infants who had been fed formula (P < 0.01), suggesting that the delay of enteral feedings in preterm infants does not permit optimal intestinal maturation of nonmucosal functions.