of SnMP in reducing bilirubin production. Journal of Perinatology (2003) 23, 507â508. doi:10.1038/sj.jp.7210943. INTRODUCTION. Sn-mesoporphyrin (SnMP) ...
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Tin-mesoporphyrin in the Treatment of Severe Hyperbilirubinemia in a Very-low-birth-weight Infant Pradeep Reddy, MD Shakuntala Najundaswamy, MD Rajeev Mehta, MD Anna Petrova, MD, PhD, MPH Thomas Hegyi, MD
Tin-mesoporphyrin (SnMP) is a competitive inhibitor of microsomal heme oxygenase (the rate-limiting enzyme in the heme catabolic pathway). It was administered as a single intramuscular dose at 46 hours of life to a verylow-birth-weight infant with severe hemolytic hyperbilirubinemia who had been awaiting an exchange transfusion. This case documents the effective elimination of the need for an exchange transfusion in a very-low-birthweight infant and is a confirmation of the experience of others for the use of SnMP in reducing bilirubin production. Journal of Perinatology (2003) 23, 507–508. doi:10.1038/sj.jp.7210943
INTRODUCTION Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase has been successfully used to decrease the production of bilirubin in neonates.1,2 However, the clinical experience of using SnMP as a treatment option in severe hyperbilirubinemia is currently limited to a few published case reports.3–6
CASE REPORT The patient was a 32-week gestation preterm male infant with a birth weight of 930 g, length of 35.5 cm, and head circumference of 25 cm. All the growth parameters were below the 10th percentile. Severe intrauterine growth restriction had been diagnosed by prenatal ultrasound. A genetic consult was inconclusive. The pregnancy was complicated by pregnancy-induced hypertension
UMDNJ-Robert Wood Johnson Medical School, Division of Neonatology, Department of Pediatrics, Saint Peter’s University Hospital, New Brunswick, NJ, USA. Address correspondence and reprint requests to Anna Petrova, MD, PhD, MPH, UMDNJ-Robert Wood Johnson Medical School, Division of Neonatology, Department of Pediatrics, Saint Peter’s University Hospital, 254 Easton Avenue, New Brunswick, NJ 08901, USA.
(PIH). The mother was admitted from the private obstetrician’s office 4 days before the delivery. The infant was born by cesarean section with Apgar scores of 5 and 8 at 1 and 5 minutes, respectively. The infant required continuous positive airway pressure (CPAP) for the first 30 hours because of mild respiratory distress. The results of the investigations for sepsis and congenital infections were negative. The mother’s and infant’s blood types were B Rh negative and B Rh positive, respectively. A direct Coombs test was positive. Infant’s blood was positive for antiC and anti-D antibodies, and negative for antigen-C. The initial total serum bilirubin (TSB) of 10.9 mg/dl was measured 15 hours following birth because of clinical jaundice. Intensive phototherapy with three banks of lights (one white light and two sets of blue lights) was started immediately after the TSB determination. In addition to the overhead lights, a biliblanket was added. After 10 hours of intense phototherapy (irradiance average: 32.2 mW/cm2/ nm) at 25 hours of life, the TSB was 15.2 mg/dl and then decreased (13 mg/dl at age 27 hours and 11.9 mg/dl at age 35 hours). However, at age 40 hours, the TSB was still very high (13.6 mg/dl) and based upon the existing guidelines8 arrangements were made by the attending neonatologist for an exchange transfusion. C-negative (antigen) blood was not available in the institution and would have to be requested from out of state. Since the bilirubin levels were increasing at approximately 0.5 mg/ dl/hour and owing to the inability to provide an immediate exchange transfusion, the decision was made to administer a single-dose of SnMP when the TSB level was 14 mg/dl in view of the risk of kernicterus (Figure 1). The Food and Drug Administration (FDA) gave approval for the use of SnMP in newborn infants on a compassionate need basis to obviate the need for exchange transfusions (protocol number 64,185-99-3WE). Saint Peter’s University Hospital Committee for the Protection of Human Subjects in Research (CPHSR) approved the compassionate use of SnMP in this infant. Parental informed consent was obtained before the administration of the drug. A single-dose of SnMP at a dose of 4.5 mg/kg was administered intramuscularly 46 hours after birth. Total and direct serum bilirubin levels were measured every 2 to 3 hours for 48 hours following the injection. After the injection, the infant received only special Blue light (Phillips F20T12/BB) phototherapy (irradiance 38.5 mW/cm2/nm for 42 hours, irradiance 24 mW/cm2/ nm for 16 hours, and 11.5 mW/cm2/nm for the following 2 days).
Journal of Perinatology 2003; 23:507–508 r 2003 Nature Publishing Group All rights reserved. 0743-8346/03 $25
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Rh-incompatibility. In this case, the intramuscular administration of a single-dose of SnMP avoided the need for an exchange transfusion. We realize that we are constrained by the fact that this a single case experience but this case demonstrates the possibility of using a single-dose of SnMP to interdict severe hyperbilirubinemia associated with Rh-isoimmunization in order to eliminate the need for an exchange transfusion in extremely low-birth-weight infants.
16 14
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Figure 1. TSB levels before and after SnMP administration in preterm infant with severe hyperbilirubinemia associated with Rh-incompatibility.
The TSB started to decrease within 10 hours after SnMP administration. There was no rebound hyperbilirubinemia. DISCUSSION The case described in this report is of a very-low-birth-weight infant with severe hemolytic hyperbilirubinemia, whose requirements for an exchange transfusion were supplanted by a single-dose of SnMP. The course of TSB (Figure 1) shows a slight increase during the first 8 hours after the SnMP injection. A gradual decline (by 13%) of TSB started 10 hours after SnMP administration. Valaes et al.1 demonstrated a statistically significant decrease in TSB levels within 24 hours after SnMP administration in preterm healthy newborns. In the case we describe here, the dynamics of TSB after SnMP administration were different as compared to the Jehovah’s Witness newborn cases.3 The timing of metalloporphyrin administration after birth may influence the dynamics of TSB production4,7 but not the high preSnMP injection TSB levels.9 No adverse effects of SnMP such as rashes or erythema were reported. We report the effective use of SnMP in a very-low-birth-weight infant with severe hyperbilirubinemia caused by Coombs-positive
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References 1. Valaes T, Petmezaki S, Henschke C, Drummond GS, Kappas A. Control of jaundice in preterm newborns by an inhibitor of bilirubin production: studies with tin-mesoporphyrin. Pediatrics 1994;93:1–11. 2. Kappas A, Drummond GS, Henschke C, Valaes T. Direct comparison of Snmesoporphyrin an inhibitor of bilirubin production and phototherapy in controlling hyperbilirubinemia in term and near-term newborns. Pediatrics 1995;95:468–74. 3. Kappas A, Drummond GS, Munson DP, Marshall JR. Sn-mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah’s Witness newborns as an alternative to exchange transfusion. Pediatrics 2001;108:1374–7. 4. Kappas A, Drummond GS, Valaes T. A single dose of Sn-mesoporphyrin prevents development of severe hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns. Pediatrics 2001;108:25–30. 5. Galbraith RA, Drummond GS, Kappas A. Suppression of bilirubin production in the Crigler–Najjar type I syndrome: studies with the heme oxygenase inhibitor tin-mesoporphyrin. Pediatrics 1992;89:175–82. 6. Rubaltalli FF, Dario C, Zancan L. Congenital nonobstructive, nonhemolytic jaundice: effect of tin-mesoporphyrin. Pediatrics 1994;95:942–4. 7. Kappas A, Drummond GS, Manola T, Petmezaki S, Valaes T. Snprotoporphyrin use in the management of hyperbilirubinemia in term newborns with direct Coombs-positive ABO incompatibility. Pediatrics 1988;81:485–97. 8. Maisels MJ. Neonatal jaundice. In: Avery GB, Fletcher MA, MacDonald M, editors. Neonatology: Pathophysiology and Management of the Newborn. Philadelphia, PA: JB Lippincott; 1994. 9. Martinez JC, Garcia HO, Otheguy LE, Drummond GS, Kappas A. Control of severe hyperbilirubinemia in full-term newborns with the inhibitor of bilirubin production Sn-mesoporphyrin. Pediatrics. 1999;108:25–30.
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