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Stannsoporfin with phototherapy to treat hyperbilirubinemia in newborn hemolytic disease

Journal of Perinatology volume 42, pages 110–115 (2022)Cite this article

Subjects

Abstract

Objective

To evaluate the efficacy and safety of tin mesoporphyrin (SnMP) in neonates with hyperbilirubinemia (HB) due to hemolysis.

Study Design

This multicenter, placebo-controlled phase 2b study (NCT01887327) randomized newborns (35–42 weeks) with hemolysis started on phototherapy (PT) to placebo (Ctrl), SnMP 3.0 mg/kg, or SnMP 4.5 mg/kg given once IM within 30 min of initiation of PT.

Results

In all, 91 patients were randomized (Ctrl: n = 30; 3 mg/kg SnMP: n = 30; 4.5 mg/kg SnMP: n = 31). At 48 h TSB significantly increased in Ctrl by 17.5% (95% CI 5.6–30.7; p = 0.004) and significantly decreased by −13% (95% CI −21.7 to −3.2; p = 0.013) in the 3.0 mg/kg and by −10.5% (95% CI −19.4 to −0.6; p = 0.041) in the 4.5 mg/kg group. Decreases in SnMP groups were significant (p < 0.0001) vs Ctrl.

Conclusion

SnMP with PT significantly reduced TSB by 48 h. SnMP may be useful as a treatment for HB in neonates with hemolysis.

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Fig. 1: Change in TSB over 48 h after treatment.

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References

  1. Kuzniewicz MW, Wickremasinghe AC, Wu YW, McCulloch CE, Walsh EM, Wi S, et al. Incidence, etiology, and outcomes of hazardous hyperbilirubinemia in newborns. Pediatrics. 2014;134:504–9.

    Article  Google Scholar 

  2. Vanburg PK, Hansen BM, Greisen G, Mathiasen R, Kasper F, Ebbesen F, et al. Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children: a Danish population-based study. Dev Med Child Neurol. 2015;57:378–84.

    Article  Google Scholar 

  3. Amin SB, Saluja A, Saili A, Orlando M, Wang H, Laroia N, et al. Chronic auditory toxicity in late preterm and term infants with significant hyperbilirubinemia. Pediatrics. 2017;140:e20164009.

    Article  Google Scholar 

  4. Rose J, Vassar R. Movement disorders due to bilirubin toxicity. Semin Fetal Neonatal Med. 2015;20:20–5.

    Article  Google Scholar 

  5. Olds C, Oghalai JS. Audiologic impairment associated with bilirubin-induced neurologic damage. Semin Fetal Neonatal Med. 2015;20:42–6.

    Article  Google Scholar 

  6. LePichon JB, Riordan SM, Watchko J, Shapiro SM. The neurologic sequelae of neonatal hyperbilirubinemia: definitions, diagnosis and treatment of kernicterus spectrum disorders. Curr Pediatr Rev. 2017;13:199–209.

  7. American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297–316.

    Article  Google Scholar 

  8. Maisels JM, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF. Hyperbilirubinemia in the newborn infant ≥35 weeks’ gestation: an update with clarifications. Pediatrics 2009;124:1193.

  9. Burgos AE, Schmidt SK, Stevenson DK, Phibbs CS. Readmission for neonatal jaundice in California, 1991–2000: trends and implications. Pediatrics. 2008;121:e864.

    Article  Google Scholar 

  10. Escobar GJ, Greene JD, Hulac P, Kincannon F, Bischoff K, Gardner MN, et al. Rehospitalization after birth hospitalization; patterns among infants of all gestations. Arch Dis Child. 2005;90:125–31.

    Article  CAS  Google Scholar 

  11. Bhutani VK. and The Committee on Fetus and newborn. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2011;128:1046–52.

    Article  Google Scholar 

  12. Wolf MF, Childers J, Gray KD, Chivily C, Glenn M, Jones L. Exchange transfusion safety and outcomes in neonatal hyperbilirubinemia. J Perinatol. 2020;40:1506–12.

    Article  Google Scholar 

  13. Zweirs C, Scheffer-Rath ME, Lopriore E, de Haas M, Lilely HG. Immunoglobulin for alloimmune hemolytic disease in neonates. Cochrane Database Syst Rev. 2018;3:CD003313.

  14. Kappas A, Drummond GS, Mamola T, Petmezaki S, Valaes T. Sn-Protoporphyrin use in the management of hyperbilirubinemia in term newborns with direct Coombs-positive ABO Incompatibility. Pediatr. 1988;81:845.

    Google Scholar 

  15. 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;94:1–11.

    Article  Google Scholar 

  16. Kappas A, Drummond GS, Henschke C, Valaes T. Direct comparison of Sn-Mesoporphyrin, an inhibitor of bilirubin production, and phototherapy in controlling hyperbilirubinemia in term and near-term newborns. Pediatrics. 1995;95:468–74.

    Article  CAS  Google Scholar 

  17. Valaes T, Drummond GS, Kappas A. Control of hyperbilirubinemia in glucose-6- phosphate dehydrogenase-deficient newborns using an inhibitor of bilirubin production, Sn-mesoporphyrin. Pediatrics. 1998;101:E1.

    Article  CAS  Google Scholar 

  18. 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.

    Article  CAS  Google Scholar 

  19. Bhutani VK, Poland R, Meloy LD, Hegyi T, Fanaroff AA, Maisels MJ. Clinical trial of tin mesoporphyrin to prevent neonatal hyperbilirubinemia. J Perinatol. 2016;36:533–9.

    Article  CAS  Google Scholar 

  20. Martinez JC, Garcia HO, Otheguy LE, Drummond CS, Kappas A. Control of severe hyperbilirubinemia in full term newborns with the inhibitor of bilirubin production. Pediatrics. 1999;103:1–5.

    Article  CAS  Google Scholar 

  21. Fort FL, Gold J. Phototoxicity of tin protoporphyrin, tin mesoporphyrin, and tin diiododeuteroporphyrin under neonatal phototherapy conditions. Pediatrics. 1989;84:1031–7.

    Article  CAS  Google Scholar 

  22. Burke BL, Robbins JM, Mac Bird T, Hobbs CA, Nesmith C, Tilford JM. Trends in hospitalization for neonatal jaundice and kernicterus in the United States, 1988-2005. Pediatrics. 2009;123:524–32.

    Article  Google Scholar 

  23. Fein EH, Friedlander S, Yu Y, Pak Y, Sakai-Bizmark R, Smith LM. Phototherapy for neonatal unconjugated hyperbilirubinemia: Examining outcomes by level of care. Hosp Pediatr. 2019;9:115–20.

    Article  Google Scholar 

  24. Newman TB, Wickremasinghe AC, Walsh EM, Grimes BA, McCulloch CE, Kuzniewicz MW. Retrospective cohort study of phototherapy and childhood cancer in Northern California. Pediatrics. 2016;137:e20151354.

    Article  Google Scholar 

  25. Ramy N, Ghany E, Alsherany W, Nada A, Darwish RK, Rabie WA, et al. Jaundice, phototherapy and DNA damage in full-term neonates. J Perinatal. 2016;36:132–6.

    Article  CAS  Google Scholar 

  26. Mokhtar WA, Sherief LM, Elsayed H, Shehab MM, El Gebaly SM, Khalil AMM, et al. Conventional intensive versus LED intensive phototherapy oxidative stress burden in neonatal hyperbilirubinemia of haemolytic origin. Paediatr Child Health. 2020;40:30–4.

    Article  Google Scholar 

  27. Sirota L, Straussberg R, Gurary N, Aloni D, Bessler H. Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells. Eruv J Pediatr. 1999;158:910–3.

    Article  CAS  Google Scholar 

  28. Aspberg S, Dahlquist G, Kahan T, Kallen B. Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma. Pediatr Allergy Immunol. 2010;21:e733–739.

    Article  Google Scholar 

  29. Dahlquist G, Kallen B. Indications that phototherapy is a risk factor for insulin-dependent diabetes. Diabetes Care. 2003;26:247–8.

    Article  Google Scholar 

  30. Lozado LE, Nylund CM, Gorman GH, Hisle-Gorman E, Erdie-Lalena CR, Kuehn D. Association of autism spectrum disorder with neonatal hyperbilirubinemia. Global Pediatr Health. 2015;2:1–5.

    Google Scholar 

  31. Newman TB, Wu YW, Kuzniewicz MW, Grimes BA, McCulloch CE. Childhood seizures after phototherapy. Pediatrics. 2018;142:e20180648.

    Article  Google Scholar 

  32. Maimburg RD, Olsen J, Sun Y. Neonatal hyperbilirubinemia and the risk of febrile seizures and childhood epilepsy. Epilepsy Res. 2016;124:67–72.

    Article  CAS  Google Scholar 

  33. Tyson JE, Pedroza C, Langer J, Green C, Morris B, Stevenson D. Does aggressive phototherapy increase mortality while decreasing profound impairment among the smallest and sickest newborn? J Perinatol. 2012;32:677–84.

    Article  CAS  Google Scholar 

  34. Smits-Wintiens VE, Rath ME, van Zwet EW, Oepkes D, Brand A, Walther FJ. Neonatal morbidity after exchange transfusion for red cell alloimmune hemolytic disease. Neonatology. 2013;103:141–7.

    Article  Google Scholar 

  35. Murray NA, Roberts I. Haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2007;92:83–8.

    Article  Google Scholar 

  36. Elsaie AL, Taleb M, Nicosia A, Zangaladze A, Pease ME, Newton K, et al. Comparison of end-tidal carbon monoxide measurements with direct antiglobulin tests in the management of neonatal hyperbilirubinemia. J Perinatol. 2020;40:1513–7.

    Article  CAS  Google Scholar 

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Acknowledgements

Infacare Pharmaceuticals designed this study to meet Phase 2B requirements of the FDA. They chose clinical sites, provided study oversight, and collected data. They were not involved in the manuscript preparation but have reviewed the manuscript. Data for this article were collected by Infacare but were analyzed independently by the authors.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Mount Sinai South Nassau Hospital, Oceanside, NY, USA

    Warren N. Rosenfeld & W. Rosenfeld

  2. Department of Pediatrics, University of Florida at Jacksonville School of Medicine, Jacksonville, FL, USA

    Mark L. Hudak, R. Alissa, S. Crawford, M. Hudak & A. Maddox

  3. Mallinckrodt Pharmaceutical, Blanchardstown, Dublin, 15, Ireland

    Nancy Ruiz

  4. Department of Medicine, University of Florida at Jacksonville School of Medicine, Jacksonville, FL, USA

    Shiva Gautam

  5. Children’s Hospital of Nevada at University Medical Center, Las Vegas, NV, USA

    F. Banfro, R. Bimbi, A. Eldemerdash & D. Reyes

  6. Arrowhead Regional Medical Center, Colton, CA, USA

    A. Barringham, A. Brown, N. Shafi & W. Wong

  7. Rutgers New Jersey Medical School, Newark, NJ, USA

    L. Bettica & O. Fofah

  8. University of TN Health Sciences Center, Memphis, TN, USA

    L. G. Camp & R. Dhanireddy

  9. Stony Brook University Hospital, Stony Brook, NY, USA

    B. Chakraborty, L. Clark & E. Maduekwe

  10. WakeMed Health, Raleigh, NC, USA

    G. Rhodes Ryan & S. Kicklighter

  11. NYU Langone Hospital, Mineola, NY, USA

    N. Hanna & S. Richter

  12. Virginia Commonwealth University, Richmond, VA, USA

    A. Jewell & L. Meloy

  13. St. Christopher’s Hospital for Children/Hahnemann, Philadelphia, PA, USA

    N. Katof, F. D. Kehinde & V. Lowery

  14. University of California San Diego Medical Center, San Diego, CA, USA

    J. Kim

  15. University of Louisville, Louisville, KY, USA

    J. Nason, D. Stewart & M. Thomas

  16. University of Texas Medical Branch-, Galveston, TX, USA

    K. Pollock & K. Shattuck

  17. Medical University of South Carolina, Charleston, SC, USA

    P. Smith & C. Wagner

Authors
  1. Warren N. Rosenfeld
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  2. Mark L. Hudak
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  4. Shiva Gautam
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Consortia

The Jasmine Study Group

  • R. Alissa
  • , F. Banfro
  • , A. Barringham
  • , L. Bettica
  • , R. Bimbi
  • , A. Brown
  • , L. G. Camp
  • , B. Chakraborty
  • , L. Clark
  • , S. Crawford
  • , R. Dhanireddy
  • , A. Eldemerdash
  • , O. Fofah
  • , G. Rhodes Ryan
  • , N. Hanna
  • , M. Hudak
  • , A. Jewell
  • , N. Katof
  • , F. D. Kehinde
  • , S. Kicklighter
  • , J. Kim
  • , V. Lowery
  • , A. Maddox
  • , E. Maduekwe
  • , L. Meloy
  • , J. Nason
  • , K. Pollock
  • , D. Reyes
  • , S. Richter
  • , W. Rosenfeld
  • , N. Shafi
  • , K. Shattuck
  • , P. Smith
  • , D. Stewart
  • , M. Thomas
  • , C. Wagner
  •  & W. Wong

Contributions

Dr. Rosenfeld was involved in the study design, drafted the original manuscript and reviewed, and revised the manuscript. Dr. Hudak coordinated and participated in Data analyses, reviewed and revised the manuscript. Dr. Gautam provided statistical analysis and reviewed the manuscript. Dr. Ruiz was involved in study design and reviewed and revised manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Warren N. Rosenfeld.

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Conflict of interest

The authors declare no competing interests.

Ethics approval and consent to participate

The study protocol, amendments, and informed consent forms were reviewed and approved by the Institutional Review Boards at each study site. This study was performed in accordance with the Declaration of Helsinki.

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Cite this article

Rosenfeld, W.N., Hudak, M.L., Ruiz, N. et al. Stannsoporfin with phototherapy to treat hyperbilirubinemia in newborn hemolytic disease. J Perinatol 42, 110–115 (2022). https://doi.org/10.1038/s41372-021-01223-2

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  • DOI: https://doi.org/10.1038/s41372-021-01223-2

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