This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT We propose to examine the absorption and excretion of zinc and copper in infants with ostomies. This will be accomplished by measuring baseline excretion and serum levels of zinc, copper, and ceruloplasmin, and by utilizing stable isotopes of zinc and copper to measure absorption and excretion. When an infant with an ostomy is receiving primarily total parenteral nutrition (TPN) with minimal or no enteral feeds, we will collect ostomy output for 24 hours to measure zinc and copper excretion, and will measure serum zinc, copper, and ceruloplasmin levels. We will utilize stable isotopes of zinc and copper at two time points: when the infant still has the ostomy and is receiving primarily enteral nutrition without TPN, and lastly, when/if the patient s ostomy is removed with the bowels reanastamosed and the patient is stable on enteral feeds. HYPOTHESIS For the first part of the study, excretion data for zinc will be obtained for ostomy patients. We hypothesize that infants with an ostomy will excrete more zinc in their stools than healthy term or preterm infants without ostomies. For the second part of the study, we will obtain data on zinc absorption, secretion, and excretion through use of stable isotopes. Jalla et al determined that healthy infants retain zinc of 0.4 mg/day. We hypothesize that due to increased zinc losses, the infants in the study will be less positive than the healthy infants in the study by Jalla et al. Our study is designed to be able to detect if the ostomy patients net retention is one-half that described by Jalla (i.e. 0.2 mg/d). We will also obtain data on copper absorption, secretion, and excretion through the use of stable isotopes in the second part of the study. As a pilot study, we do not fully know what to expect regarding copper levels in infants with ostomies, but we hypothesize that they may be less positive than healthy infants without ostomies. Also, we hypothesize that zinc and copper are competitively absorbed in the gut;therefore, infants who receive more zinc may absorb less copper. For the third part of the study, we will obtain data on zinc absorption through the use of stable isotopes after the infant has had surgery to reanastamose the bowel. We hypothesize that there may be continued zinc losses above those documented for healthy infants who have never had an ostomy, but decreased losses compared to when the infant had an ostomy.
SPECIFIC AIMS To determine how the presence of an ileostomy impacts zinc and copper metabolism in infants at three time points: when the infant has an ostomy and is receiving the majority of calories from total parenteral nutrition (TPN) when the infant has an ostomy and is receiving primarily enteral nutrition without TPN;and when/if the infant has a surgery to reconnect the bowel and is receiving primarily enteral nutrition. The primary objective of this study revolves around part 2, the stable isotope portion of zinc and copper absorption, secretion, and excretion in infants with an ostomy. There is currently no data available in this population for zinc balance. Additional objectives that will be accomplished by the study include establishment of baseline secretion of zinc while on TPN in part one of the study, and determination of the effect of reanastamosis on zinc secretion in the third part of the study. There is currently no data available in this population for copper balance. Pilot data regarding copper absorption and levels will be obtained at part 2 of the study. BACKGROUND AND SIGNIFICANCE The current neonatal intensive care unit &(NICU) population has a substantial number of infants who have ostomies. These are related to congenital malformations and to damage to the intestine related to post-natal conditions such as necrotizing enterocolitis (NEC). Preterm infants are at high risk of NEC, the most common surgical emergency in preterm infants. Severe cases of NEC require surgery to remove the damaged portions of bowel. If surgery is required, it is not uncommon for the surgeon to create an ostomy (ileostomy or colostomy), an opening from an area inside the body to the outside. NEC is the most common reason for an infant to need an ostomy, but infants sometimes have other problems that would require placement of an ostomy. Some of these problems include intestinal atresias, such as duodenal or ileal atresia, or isolated gastrointestinal perforations. Nutritional management is central to the care of preterm infants with ostomies. Currently, there are two nutritional manipulations that are routinely done in these babies that this study will be addressing. First, additional supplementary zinc is added to the intravenous nutrition, also called total parenteral nutrition (TPN). Bile and pancreatic secretions contain large amounts of zinc, and these are secreted into the duodenum, the first part of the small intestine. Usually, the zinc is reabsorbed further down the digestive tract. However, if the baby has an ostomy, the zinc never gets to the part of the bowel where it is reabsorbed, so it is excreted too early in stool into the ostomy. In order to try to prevent excessive zinc losses and subsequent negative zinc balance, the amount of intravenous zinc given in TPN is usually doubled from 400 mcg/kg/d to 800 mcg/kg/d. Currently, we do not have any data to know if doubling parenteral zinc intake is sufficient to prevent the development of negative zinc balance in preterm infants with ostomies. Secondly, trace minerals (such as copper) are limited in the TPN. Infants who have an ostomy are at risk for having trouble tolerating feedings, so they have to be on TPN for a long time. When babies are on TPN for a prolonged period of time (greater than 2-4 weeks), they can develop cholestasis. Cholestasis is a condition in which little or no bile is secreted or the flow of bile into the digestive tract is obstructed. Bile backs up in the gallbladder and eventually the liver. It can damage the liver, even to the point of liver failure in severe cases. Copper is one of the trace minerals that are normally given daily in the TPN, but about 50% of copper is excreted from the body through the bile. If the bile flow is blocked or slowed, as in cholestasis, it is usual practice to either give the trace minerals less frequently (twice a week compared to daily), or to limit them completely. This is done partly as copper losses are expected to be reduced in cholestasis, and partly because deposition of copper in the liver may worsen cholestasis. Currently, we do not know how large an effect cholestasis has on copper balance.
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