Abstract

 

Objective: Neonatal jaundice, caused by elevated bilirubin levels, may lead to severe neurological complications, particularly in preterm infants. The aim of this study was to evaluate the predictive value of early carboxyhemoglobin (COHb) levels for identifying indirect hyperbilirubinemia and the need for phototherapy in preterm neonates.

Materials and Methods: This retrospective study included 297 preterm infants admitted to the neonatal intensive care unit (NICU). COHb, bilirubin, and related laboratory parameters were evaluated at 0–6 hours, 24 hours, and 48–96 hours after birth. Statistical analyses included the Mann–Whitney U test, Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and logistic regression.

Results: Among 297 preterm newborns, 151 (50.8%) required phototherapy. Early COHb levels showed only very weak correlations with subsequent bilirubin concentrations. COHb levels at 0–6 hours and 24 hours demonstrated poor discriminatory performance for phototherapy requirement, with AUC values of 0.560 and 0.583, respectively. Neither measurement was independently associated with phototherapy requirement in multivariable analyses, whereas birth weight <2000 g remained an independent determinant in both models.

Conclusion: Although early COHb levels showed weak correlations with indirect bilirubin levels in preterm neonates, they were not reliable independent predictors of phototherapy requirement. These findings suggest that COHb has limited clinical utility as a standalone biomarker for guiding treatment decisions.

References

  1. Hansen, T.D. Bratlid, Physiology of neonatal unconjugated hyperbilirubinemia. Care of Jaundiced Neonate. New York: McGraw-Hill, 2012: p. 65-95.
  2. Bhutani VKL. Bilirubin-induced neurologic dysfunction (BIND). Seminars in Fetal and Neonatal Medicine 2015;20(1):1. https://doi.org/10.1016/j.siny.2014.12.010
  3. Kaplan M, Maurizio M, Cathy H, et al. Imbalance between production and conjugation of bilirubin: a fundamental concept in the mechanism of neonatal jaundice. Pediatrics, 2002;110(4): e47-e47. https://doi.org/10.1542/peds.110.4.e47
  4. Kaplan MP, Merlob R. Regev, Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus. J Perinatol. 2008;28(6):389-7. https://doi.org/10.1038/jp.2008.20
  5. Kramer L. Advancement of dermal icterus in the jaundiced newborn. Am J Dis Child 1969;118(3): 454-8. https://doi.org/10.1001/archpedi.1969.02100040456007
  6. Bhutani VK, Gourley GR, Adler S et. al. Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia. Pediatrics, 2000; 106(2): p. e17-e17. https://doi.org/10.1542/peds.106.2.e17
  7. Wainer S, Rabi Y, Parmar SM, Allegro D, Lyon M. Impact of skin tone on the performance of a transcutaneous jaundice meter. Acta Paediatr. 2009;98(12):1909-15. https://doi.org/10.1111/j.1651-2227.2009.01497.x
  8. Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics, 2004;114(1): 297-316. https://doi.org/10.1542/peds.114.1.297
  9. Kalakonda A, Jenkins BA, John S. Physiology, Bilirubin. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 12, 2022.
  10. Wong R, Kaplan M, Sibley E, Stevenson D. Neonatal jaundice and liver disease: Martin RJ. Fanaroff and Martin’s neonatal-perinatal medicine: diseases of the fetüs and infant. 8th ed, Philadelphia, Pa. Mosby Elsevier, 2006.
  11. Shapiro S, Bhutani K, Johnson L. Hyperbilirubinemia and kernicterus. Clinics in perinatology, 2006; 33(2): 387-410. https://doi.org/10.1016/j.clp.2006.03.010
  12. Amos RC, Jacob H, Leith W. Jaundice in newborn babies under 28 days: NICE guideline 2016 (CG98). Arch Dis Child Educ Pract Ed. 2017;102(4):207-9. https://doi.org/10.1136/archdischild-2016-311556
  13. Van de Bor M, Van Zeben-van der A, Verloove-Vanhorick T, Brand P, Ruys J. Hyperbilirubinemia in preterm infants and neurodevelopmental outcome at 2 years ofage: results of a national collaborative survey. Pediatrics, 1989;83(6): 915-20. https://doi.org/10.1542/peds.83.6.915
  14. Çoban A, Türkmen MK, Gürsoy T. Turkish Neonatal Society guideline to the approach, follow-up, and treatment of neonatal jaundice. Turk Pediatri Ars. 2018;53(Suppl 1):S172-9. https://doi.org/10.5152/TurkPediatriArs.2018.01816
  15. Ünal S, Eker S, Kılıç G, Yılmaz A. Özaydın E. Retrospective Analysis of theNeonates with Indirect Hyperbilirubinemia. Türkiye Klinikleri J Pediatr, 2008;17(4):223-9.
  16. Günel M. Evaluation of neonates with the diagnosis of indirect hyperbilirubinemia followed up at the pediatric clinics of Dicle University Hospital between 2007 and 2009. medical residency thesis, Diyarbakır, 2010.
  17. Phuapradit W, Chaturachinda K, Auntlamai S. Risk factors for neonatal hyperbilirubinemia. J Med Assoc Thai. 1993;76(8):424-8.
  18. İlhan T, Salihoğlu Ö, Demirelli Y, Hatipoğlu S. Clinical and laboratory characteristics and associated risk factors of infants hospitalized in neonatal unit due to indirect hyperbilirubinemia. J Clin Exp Invest, 2012;3(1):38-43. https://doi.org/10.5799/ahinjs.01.2012.01.0108
  19. Gale R, Seidman D, Dollberg S, Stevenson D. Epidemiology of neonatal jaundice in the Jerusalem population. J Pediatr Gastroenterol Nutr. 1990;10(1):82-6. https://doi.org/10.1097/00005176-199001000-00016
  20. Engel R, Popelka G. Single breath CO measurements normalized to 5% CO2 in Coombs test positive neonates. Physiol Meas. 2007;28(9):977-88. https://doi.org/10.1088/0967-3334/28/9/001
  21. Bhutani V, Srinivas S, Castillo Cuadrado M, et al. Identification of neonatal hemolysis: an approach to predischarge management of neonatal hyperbilirubinemia. Acta Paediatr 2016;105(5): e189-e194. https://doi.org/10.1111/apa.13341
  22. Bailey D, Fuchs H, Hentschel R. Carboxyhemoglobin the forgotten parameter of neonatal hyperbilirubinemia. J Perinat Med. 2017;45(5): 613-7. https://doi.org/10.1515/jpm-2016-0053
  23. Yingying Bao, Jiajun Zhu, Lixin Ma, et.al. End-Tidal Carbon Monoxide Nomogram for Term and Late-Preterm Chinese Newborns. J Pediatr. 2022;250:16-21.e3. https://doi.org/10.1016/j.jpeds.2022.07.003
  24. Okwundu CI, Bhutani VK, Uthman OA, et.al. Transcutaneous bilirubinometry for detecting jaundice in term or late preterm neonates. Cochrane Database Syst Rev 2024;5(5): CD011060. https://doi.org/10.1002/14651858
  25. Karabulut B, Arcagok B. A neglected and promising predictor of severe hyperbilirubinemia due to hemolysis: carboxyhemoglobin. Fetal pediatr pathol 2020;39(2):124-31. https://doi.org/10.1080/15513815.2019.1641862
  26. Tıraş M, Can E, Hamilçıkan Ş. Role of Cord Blood Carboxyhemoglobin in Detecting Significant Hyperbilirubinemia in Term Neonates with ABO Alloimmunization. Am J Perinatol. 2022;39(12):1321-5. https://doi.org/10.1055/s-0040-1722328
  27. Guney Varal I, Mengi S, Dogan P et al. Elevated blood COHb levels as an early predictor of phototherapy requirement in moderate and late preterm infants. J Maternal‐Fet Neonat Med 2020; 33:1441-6. https://doi.org/10.1080/14767058.2018.1542675

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Copyright © 2026 The Author(s). This is an open access article distributed under the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Bahar YF, Ongun H, Kıhtır Z, Çelik K, Arayıcı S. Relationship between carboxyhemoglobin levels and indirect hyperbilirubinemia in preterm newborns. Turk J Pediatr Dis. 2026;Early View:1-7. https://doi.org/10.12956/TJPD.2026.1355