Our objective is to study bilirubin metabolism in human neonates, focusing on those neonatal conditions in which increased bilirubin production is believed to be an important causative factor in the hyperbilirubinemic state. In order to further study the mechanism(s) of increased bilirubin production, and to evaluate an experimental method which can decrease bilirubin production in the clinical setting, rhesus neonate models will be created for important aspects of each of the human neonatal conditions being studied.
The specific aim of the proposed studies in human neonates is to measure bilirubin production under the following clinically relevant circumstances: developmental jaundice (e.g., a randomized clinical trial of supplemental vitamin E or placebo in ventilated premature babies with a birth weight less than or equal to 1,500 gm); intrauterine acceleration of growth (e.g., infants of diabetic mothers); obstructive jaundice (e.g., babies with a birth weight less than or equal to 1,500 gm on total parenteral nutrition); and neonatal drug exposure (e.g., maternal epidural anesthesia with bupivacaine).
The specific aim of the proposed studies in rhesus neonates is to explore the mechanism(s) of bilirubin production in the selected models: hemolytic jaundice; the hyperinsulinemic rhesus fetus; common bile duct ligation; and neonatal drug exposure. We will also attempt to decrease bilirubin production in these models using tin protoporphyrin. The methodology will include noninvasive techniques for detecting CO in breath to estimate in vivo bilirubin production as well as ethane and pentane in breath to estimate in vivo lipid peroxidation. Blood measurements will include hemoglobin, carboxyhemoglobin, bilirubin, bitamin E, total lipids and free fatty acids, erythropoietin, and insulin levels. Bilirubin and vitamin E will be measured by high performance liquid chromatography. Other measurements will include the peroxide hemolysis test and red blood cell life span. Heme oxygenase activity measured by gas chromatography, UDPG glucuronyl transferase activity, and heme, tin protoporphyrin, and tin levels will be measured in selected tissues from the monkeys.
The specific aims are based on one main hypothesis: that increased bilirubin production is an important factor contributing to neonatal jaundice. As a corollary, we hypothesize that increase RBC destruction is the most common cause of this increased bilirubin production under most circumstances. Furthermore, tin protoporphyrin can be used to suppress bilirubin production when this is the case.
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| Meny, Robert G; Vreman, Hendrik J; Stevenson, David K et al. (2002) Failure to detect elevated levels of carboxyhemoglobin in infants dying from SIDS. J Forensic Sci 47:660-2 |
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| Hayde, M; Pollak, A; Bernaschek, G et al. (2000) Association of fetal and maternal carboxyhemoglobin levels in normal and Rh-alloimmune pregnancies. Early Hum Dev 58:205-12 |
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