Perinatal/Neonatal ...... Case Presentation Tin-mesoporphyrin in the Treatment of Severe Hyperbilirubinemia in a Very-low-birth-weight

Pradeep Reddy, MD (PIH). The mother was admitted from the private obstetrician’s Shakuntala Najundaswamy, MD office 4 days before the delivery. The infant was born by cesarean Rajeev Mehta, MD section with Apgar scores of 5 and 8 at 1 and 5 minutes, Anna Petrova, MD, PhD, MPH respectively. The infant required continuous positive airway Thomas Hegyi, MD pressure (CPAP) for the first 30 hours because of mild respiratory distress. The results of the investigations for and congenital infections were negative. The mother’s and infant’s types were B Rh negative and B Rh positive, respectively. A Tin-mesoporphyrin (SnMP) is a competitive inhibitor of microsomal heme direct was positive. Infant’s blood was positive for anti- oxygenase (the rate-limiting enzyme in the heme catabolic pathway). It was C and anti-D antibodies, and negative for antigen-C. The initial administered as a single intramuscular dose at 46 hours of life to a very- total serum (TSB) of 10.9 mg/dl was measured 15 hours low-birth-weight infant with severe hemolytic hyperbilirubinemia who had following birth because of clinical . Intensive phototherapy been awaiting an . This case documents the effective with three banks of lights (one white light and two sets of blue elimination of the need for an exchange transfusion in a very-low-birth- lights) was started immediately after the TSB determination. In weight infant and is a confirmation of the experience of others for the use addition to the overhead lights, a was added. After 10 2 of SnMP in reducing bilirubin production. hours of intense phototherapy (irradiance average: 32.2 mW/cm / Journal of Perinatology (2003) 23, 507–508. doi:10.1038/sj.jp.7210943 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 INTRODUCTION arrangements were made by the attending neonatologist for an exchange transfusion. C-negative (antigen) blood was not available Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase in the institution and would have to be requested from out of state. has been successfully used to decrease the production of Since the bilirubin levels were increasing at approximately 0.5 mg/ bilirubin in neonates.1,2 However, the clinical experience of using dl/hour and owing to the inability to provide an immediate SnMP as a treatment option in severe hyperbilirubinemia is exchange transfusion, the decision was made to administer a currently limited to a few published case reports.3–6 single-dose of SnMP when the TSB level was 14 mg/dl in view of the risk of (Figure 1). The Food and Drug Administration (FDA) gave approval for CASE REPORT the use of SnMP in newborn on a compassionate The patient was a 32-week gestation preterm male infant with a need basis to obviate the need for exchange transfusions (protocol of 930 g, length of 35.5 cm, and head circumference of number 64,185-99-3WE). Saint Peter’s University Hospital 25 cm. All the growth parameters were below the 10th percentile. Committee for the Protection of Human Subjects in Research Severe intrauterine growth restriction had been diagnosed by (CPHSR) approved the compassionate use of SnMP in this infant. prenatal ultrasound. A genetic consult was inconclusive. The Parental informed consent was obtained before the administration was complicated by pregnancy-induced hypertension 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 UMDNJ-Robert Wood Johnson Medical School, Division of , Department of , Saint Peter’s University Hospital, New Brunswick, NJ, USA. 48 hours following the injection. After the injection, the infant received only special Blue light (Phillips F20T12/BB) phototherapy Address correspondence and reprint requests to Anna Petrova, MD, PhD, MPH, UMDNJ-Robert 2 2 Wood Johnson Medical School, Division of Neonatology, Department of Pediatrics, Saint Peter’s (irradiance 38.5 mW/cm /nm for 42 hours, irradiance 24 mW/cm / 2 University Hospital, 254 Easton Avenue, New Brunswick, NJ 08901, USA. nm for 16 hours, and 11.5 mW/cm /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 www.nature.com/jp 507 Reddy et al. Tin-mesoporphyrin and Severe Hyperbilirubinemia

16 Rh-incompatibility. In this case, the intramuscular administration of a single-dose of SnMP avoided the need for an exchange 14 transfusion. 12 We realize that we are constrained by the fact that this a SnMP single case experience but this case demonstrates the possibility 10 of using a single-dose of SnMP to interdict severe 8 hyperbilirubinemia associated with Rh-isoimmunization in order TSB (mg/dL) to eliminate the need for an exchange transfusion in extremely 6 low-birth-weight infants. 4

2 0102030405060708090100 Hours of Age References Figure 1. TSB levels before and after SnMP administration in preterm 1. Valaes T, Petmezaki S, Henschke C, Drummond GS, Kappas A. Control of infant with severe hyperbilirubinemia associated with Rh-incompat- jaundice in preterm newborns by an inhibitor of bilirubin production: ibility. studies with tin-mesoporphyrin. Pediatrics 1994;93:1–11. 2. Kappas A, Drummond GS, Henschke C, Valaes T. Direct comparison of Sn- The TSB started to decrease within 10 hours after SnMP mesoporphyrin an inhibitor of bilirubin production and phototherapy in administration. There was no rebound hyperbilirubinemia. controlling hyperbilirubinemia in term and near-term newborns. Pediatrics 1995;95:468–74. 3. Kappas A, Drummond GS, Munson DP, Marshall JR. Sn-mesoporphyrin DISCUSSION interdiction of severe hyperbilirubinemia in Jehovah’s Witness newborns as an alternative to exchange transfusion. Pediatrics 2001;108:1374–7. The case described in this report is of a very-low-birth-weight 4. Kappas A, Drummond GS, Valaes T. A single dose of Sn-mesoporphyrin infant with severe hemolytic hyperbilirubinemia, whose prevents development of severe hyperbilirubinemia in glucose-6-phosphate requirements for an exchange transfusion were supplanted by a dehydrogenase-deficient newborns. Pediatrics 2001;108:25–30. single-dose of SnMP. The course of TSB (Figure 1) shows a slight 5. Galbraith RA, Drummond GS, Kappas A. Suppression of bilirubin increase during the first 8 hours after the SnMP injection. A production in the Crigler–Najjar type I syndrome: studies with the heme gradual decline (by 13%) of TSB started 10 hours after SnMP oxygenase inhibitor tin-mesoporphyrin. Pediatrics 1992;89:175–82. administration. Valaes et al.1 demonstrated a statistically 6. Rubaltalli FF, Dario C, Zancan L. Congenital nonobstructive, nonhemolytic significant decrease in TSB levels within 24 hours after SnMP jaundice: effect of tin-mesoporphyrin. Pediatrics 1994;95:942–4. administration in preterm healthy newborns. In the case we 7. Kappas A, Drummond GS, Manola T, Petmezaki S, Valaes T. Sn- describe here, the dynamics of TSB after SnMP administration were protoporphyrin use in the management of hyperbilirubinemia in term different as compared to the Jehovah’s Witness newborn cases.3 The newborns with direct Coombs-positive ABO incompatibility. Pediatrics 1988;81:485–97. timing of metalloporphyrin administration after birth may 4,7 8. Maisels MJ. . In: Avery GB, Fletcher MA, MacDonald M, influence the dynamics of TSB production but not the high pre- editors. Neonatology: Pathophysiology and Management of the Newborn. 9 SnMP injection TSB levels. No adverse effects of SnMP such as Philadelphia, PA: JB Lippincott; 1994. rashes or erythema were reported. 9. Martinez JC, Garcia HO, Otheguy LE, Drummond GS, Kappas A. Control of We report the effective use of SnMP in a very-low-birth-weight severe hyperbilirubinemia in full-term newborns with the inhibitor of infant with severe hyperbilirubinemia caused by Coombs-positive bilirubin production Sn-mesoporphyrin. Pediatrics. 1999;108:25–30.

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