Login Register Cart 0
Generic placeholder image

Current Pediatric Reviews

Editor-in-Chief

ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Perinatal Hemolytic Disorders and Identification Using End Tidal Breath Carbon Monoxide

Author(s): Robert D. Christensen*, Timothy M. Bahr, Sasikarn Pakdeeto, Sarayut Supapannachart and Huayan Zhang

Volume 19, Issue 4, 2023

Published on: 21 December, 2022

Page: [376 - 387] Pages: 12

DOI: 10.2174/1573396319666221220095522

Price: $65

Abstract

Hemolytic disorders can cause severe morbidity or can be life-threatening. Before the recent development of practical and inexpensive testing for hemolysis by quantifying carbon monoxide in end-tidal breath, some hemolytic disorders in perinatal patients were not detected until severely problematic hyperbilirubinemia and/or anemia occurred. Here we review studies aimed at establishing the normal reference intervals for end tidal breath carbon monoxide (ETCO) in various perinatal populations. We also review reports, and new theories, about using this methodology to diagnose and quantify hemolytic disorders in term and premature neonates, anemic pregnant women, and fetuses in utero. The purposes of making these measurements are to; (1) identify patients who have hemolytic disorders, (2) characterize the severity of the hemolysis in each hemolytic patient, and (3) predict and prevent co-morbidities, thereby improving outcomes.

Keywords: Hemolysis, jaundice, anemia, fetus, neonate, end-tidal CO.

« Previous Next »
Graphical Abstract

[1]
Quigley JG, Means Rr RT, Glader B. The birth, life, and death of red blood cells: Erythropoiesis, the mature red blood cell, and cell destruction. In: Wintrobe’s Clinical Hematology. 14th edition. Wolthers Kluwer: Philadelphia, PA 2019; pp. 94-5.
[2]
Tidmarsh GF, Wong RJ, Stevenson DK. End-tidal carbon monoxide and hemolysis. J Perinatol 2014; 34(8): 577-81.
[http://dx.doi.org/10.1038/jp.2014.66] [PMID: 24743136]
[3]
Maisels MJ, Pathak A, Nelson NM, Nathan DG, Smith CA. Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants. J Clin Invest 1971; 50(1): 1-8.
[http://dx.doi.org/10.1172/JCI106463] [PMID: 5543875]
[4]
Maisels MJ, Pathak A, Nelson NM. The effect of exchange transfusion on endogenous carbon monoxide production in erythroblastotic infants. J Pediatr 1972; 81(4): 705-9.
[http://dx.doi.org/10.1016/S0022-3476(72)80089-1] [PMID: 4672588]
[5]
Strocchi A, Schwartz S, Ellefson M, Engel RR, Medina A, Levitt MD. A simple carbon monoxide breath test to estimate erythrocyte turno-ver. J Lab Clin Med 1992; 120(3): 392-9.
[PMID: 1517686]
[6]
Stevenson DK, Fanaroff AA, Maisels MJ, et al. Prediction of hyperbilirubinemia in near-term and term infants. J Perinatol 2001; 21(S1): S63-72.
[http://dx.doi.org/10.1038/sj.jp.7210638] [PMID: 11803421]
[7]
Christensen RD, Yaish HM, Lemons RS. Neonatal hemolytic jaundice: Morphologic features of erythrocytes that will help you diagnose the underlying condition. Neonatology 2014; 105(4): 243-9.
[http://dx.doi.org/10.1159/000357378] [PMID: 24526179]
[8]
Yaish HM, Christensen RD, Lemons RS. Neonatal nonimmune hemolytic anemia. Curr Opin Pediatr 2017; 29(1): 12-9.
[http://dx.doi.org/10.1097/MOP.0000000000000440] [PMID: 27861255]
[9]
Gallagher PG. Diagnosis and management of rare congenital nonimmune hemolytic disease. Hematology 2015; 2015(1): 392-9.
[http://dx.doi.org/10.1182/asheducation-2015.1.392] [PMID: 26637748]
[10]
Kaplan M, Wong RJ, Stevenson DK. Hemolysis and glucose-6-phosphate dehydrogenase deficiency-related neonatal hyperbilirubinemia. Neonatology 2018; 114(3): 223-5.
[http://dx.doi.org/10.1159/000489820] [PMID: 29940590]
[11]
Grace RF, Barcellini W. Management of pyruvate kinase deficiency in children and adults. Blood 2020; 136(11): 1241-9.
[http://dx.doi.org/10.1182/blood.2019000945] [PMID: 32702739]
[12]
Jiang H, Zhou JY, Li J, Li DZ. Unstable hemoglobin variants: The need for clinical vigilance in infants with congenital jaundice. Hemoglobin 2019; 43(1): 60-2.
[http://dx.doi.org/10.1080/03630269.2019.1582429] [PMID: 31092072]
[13]
Harewood J, Azevedo AM. Alpha Thalassemia. In: StatPearls. Treasure Island (FL): StatPearls Publishing 2021.
[14]
Goonasekera HW, Paththinige CS, Dissanayake VHW. Population screening for hemoglobinopathies. Annu Rev Genomics Hum Genet 2018; 19(1): 355-80.
[http://dx.doi.org/10.1146/annurev-genom-091416-035451] [PMID: 29751732]
[15]
Rets A, Clayton AL, Christensen RD, Agarwal AM. Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbiliru-binemia. Int J Lab Hematol 2019; 41 (Suppl. 1): 95-101.
[http://dx.doi.org/10.1111/ijlh.13014] [PMID: 31069991]
[16]
Agarwal AM, Nussenzveig RH, Reading NS, et al. Clinical utility of next-generation sequencing in the diagnosis of hereditary haemolytic anaemias. Br J Haematol 2016; 174(5): 806-14.
[http://dx.doi.org/10.1111/bjh.14131] [PMID: 27292444]
[17]
Diamond LK, Blackfan KD, Baty JM. Erythroblastosis fetalis and its association with universal edema of the fetus, icterus gravis neonato-rum and anemia of the newborn. J Pediatr 1932; 1(3): 269-309.
[http://dx.doi.org/10.1016/S0022-3476(32)80057-0]
[18]
Landsteiner K, Wiener AS. An agglutinable factor in human blood recognized by immune sera for Rhesus blood. Exp Biol Med 1940; 43(1): 223.
[http://dx.doi.org/10.3181/00379727-43-11151]
[19]
Jackson ME, Baker JM. Hemolytic disease of the fetus and newborn: Historical and current state. Clin Lab Med 2021; 41(1): 133-51.
[http://dx.doi.org/10.1016/j.cll.2020.10.009] [PMID: 33494881]
[20]
Slootweg YM, Lindenburg IT, Koelewijn JM, Van Kamp IL, Oepkes D, De Haas M. Predicting anti-Kell-mediated hemolytic disease of the fetus and newborn: Diagnostic accuracy of laboratory management. Am J Obstet Gynecol 2018; 219(4): 393.e1-8.
[http://dx.doi.org/10.1016/j.ajog.2018.07.020] [PMID: 30063902]
[21]
Vats K, Watchko JF. Coordinating care across the perinatal continuum in hemolytic disease of the fetus and newborn: The timely handoff of a positive maternal anti-erythrocyte antibody Screen. J Pediatr 2019; 214: 212-6.
[http://dx.doi.org/10.1016/j.jpeds.2019.07.014] [PMID: 31451186]
[22]
Castillo Cuadrado ME, Bhutani VK, Aby JL, Vreman HJ, Wong RJ, Stevenson DK. Evaluation of a new end-tidal carbon monoxide moni-tor from the bench to the bedside. Acta Paediatr 2015; 104(6): e279-82.
[http://dx.doi.org/10.1111/apa.12938] [PMID: 25640053]
[23]
Bhutani VK, Wong RJ, Vreman HJ, Stevenson DK. Bilirubin production and hour-specific bilirubin levels. J Perinatol 2015; 35(9): 735-8.
[http://dx.doi.org/10.1038/jp.2015.32] [PMID: 25880796]
[24]
Widness JA, Lowe LS, Stevenson DK, et al. Direct relationship of fetal carboxyhemoglobin with hemolysis in alloimmunized pregnancies. Pediatr Res 1994; 35(6): 713-9.
[http://dx.doi.org/10.1203/00006450-199406000-00018] [PMID: 7936824]
[25]
Christensen RD, Ilstrup SJ, Baer VL, Lambert DK. Increased hemolysis after administering intravenous immunoglobulin to a neonate with erythroblastosis fetalis due to Rh hemolytic disease. Transfusion 2015; 55(6): 1365-6.
[http://dx.doi.org/10.1111/trf.13104] [PMID: 26074177]
[26]
Huh HJ, Chung JW, Chae SL. Microscopic schistocyte determination according to International Council for Standardization in Hematology recommendations in various diseases. Int J Lab Hematol 2013; 35(5): 542-7.
[http://dx.doi.org/10.1111/ijlh.12059] [PMID: 23480787]
[27]
Judkins AJ, MacQueen BC, Christensen RD, Henry E, Snow GL, Bennett ST. Automated quantification of fragmented red blood cells: Neonatal reference intervals and clinical disorders of neonatal intensive care unit patients with high values. Neonatology 2019; 115(1): 5-12.
[http://dx.doi.org/10.1159/000491626] [PMID: 30184540]
[28]
Hisasue M, Ai T, Kimura K, et al. Modification of the algorithm used by automated hematology analyzer XN-3000 improves specificity in the detection of schistocytes. Clin Lab 2021; 67(01/2021): 67.
[http://dx.doi.org/10.7754/Clin.Lab.2020.200227] [PMID: 33491415]
[29]
Bahr TM, Judkins AJ, Christensen RD, et al. Neonates with suspected microangiopathic disorders: Performance of standard manual schistocyte enumeration vs. the automated fragmented red cell count. J Perinatol 2019; 39(11): 1555-61.
[http://dx.doi.org/10.1038/s41372-019-0482-y] [PMID: 31462723]
[30]
Morse EE, Nashed A, Spilove L. Automated differential leukocyte counts. Ann Clin Lab Sci 1989; 19(3): 155-60.
[PMID: 2658725]
[31]
MacQueen BC, Christensen RD, Yoder BA, et al. Comparing automated vs manual leukocyte differential counts for quantifying the ‘left shift’ in the blood of neonates. J Perinatol 2016; 36(10): 843-8.
[http://dx.doi.org/10.1038/jp.2016.92] [PMID: 27279079]
[32]
Newman TB, Xiong B, Gonzales VM, Escobar GJ. Prediction and prevention of extreme neonatal hyperbilirubinemia in a mature health maintenance organization. Arch Pediatr Adolesc Med 2000; 154(11): 1140-7.
[http://dx.doi.org/10.1001/archpedi.154.11.1140] [PMID: 11074857]
[33]
Bhutani VK, Stark AR, Lazzeroni LC, et al. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr 2013; 162(3): 477-482.e1.
[http://dx.doi.org/10.1016/j.jpeds.2012.08.022] [PMID: 23043681]
[34]
Maisels MJ, Gifford K, Antle CE, Leib GR. Jaundice in the healthy newborn infant: A new approach to an old problem. Pediatrics 1988; 81(4): 505-11.
[PMID: 3353184]
[35]
Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol 2009; 29(S1): S25-45.
[http://dx.doi.org/10.1038/jp.2008.211] [PMID: 19177057]
[36]
Christensen RD, Nussenzveig RH, Yaish HM, Henry E, Eggert LD, Agarwal AM. Causes of hemolysis in neonates with extreme hyperbili-rubinemia. J Perinatol 2014; 34(8): 616-9.
[http://dx.doi.org/10.1038/jp.2014.68] [PMID: 24762414]
[37]
Ahn HS, Chang YW, Lee DW, Kwon KH, Yang SB. An incidentally detected hepatic subcapsular hematoma in a very low birth weight newborn: A case report. Cases J 2010; 3(1): 32.
[http://dx.doi.org/10.1186/1757-1626-3-32]
[38]
Legge N, Guaran R. Critical bleeding protocol for infants used for a catastrophic subgaleal haemorrhage. J Paediatr Child Health 2021. Epub ahead of print
[http://dx.doi.org/10.1111/jpc.15591] [PMID: 34043250]
[39]
Colditz MJ, Lai MM, Cartwright DW, Colditz PB. Subgaleal haemorrhage in the newborn: A call for early diagnosis and aggressive man-agement. J Paediatr Child Health 2015; 51(2): 140-6.
[http://dx.doi.org/10.1111/jpc.12698] [PMID: 25109786]
[40]
Alabsi SY, Layland T. Adrenal hemorrhage in neonates: Unusual presentation. Neonatal Netw 2015; 34(4): 220-6.
[http://dx.doi.org/10.1891/0730-0832.34.4.220] [PMID: 26802636]
[41]
Ryerson LM, Wechsler SB, Ohye RG. Hemolytic anemia secondary to modified blalock-taussig shunt. Pediatr Cardiol 2007; 28(3): 238-40.
[http://dx.doi.org/10.1007/s00246-006-1410-4] [PMID: 17437150]
[42]
Batton DG, Amanullah A, Comstock C. Fetal schistocytic hemolytic anemia and umbilical vein varix. Am J Pediatr Hematol Oncol 2000; 22(3): 259-61.
[http://dx.doi.org/10.1097/00043426-200005000-00013] [PMID: 10864059]
[43]
Christensen RD, Lambert DK, Henry E, Yaish HM, Prchal JT. End-tidal carbon monoxide as an indicator of the hemolytic rate. Blood Cells Mol Dis 2015; 54(3): 292-6.
[http://dx.doi.org/10.1016/j.bcmd.2014.11.018] [PMID: 25624169]
[44]
Christensen RD, Malleske DT, Lambert DK, et al. Measuring end-tidal carbon monoxide of jaundiced neonates in the birth hospital to identify those with hemolysis. Neonatology 2016; 109(1): 1-5.
[http://dx.doi.org/10.1159/000438482] [PMID: 26394287]
[45]
Bhutani VK, Srinivas S, Castillo Cuadrado ME, Aby JL, Wong RJ, Stevenson DK. Identification of neonatal haemolysis: An approach to predischarge management of neonatal hyperbilirubinemia. Acta Paediatr 2016; 105(5): e189-94.
[http://dx.doi.org/10.1111/apa.13341] [PMID: 26802319]
[46]
Bhutani VK, Maisels MJ, Schutzman DL, et al. Identification of risk for neonatal haemolysis. Acta Paediatr 2018; 107(8): 1350-6.
[http://dx.doi.org/10.1111/apa.14316] [PMID: 29532503]
[47]
Elsaie AL, Taleb M, Nicosia A, et al. Comparison of end-tidal carbon monoxide measurements with direct antiglobulin tests in the man-agement of neonatal hyperbilirubinemia. J Perinatol 2020; 40(10): 1513-7.
[http://dx.doi.org/10.1038/s41372-020-0652-y] [PMID: 32203175]
[48]
Maisels MJ, Kring EA, Coffey MP. Heme catabolism and bilirubin production in readmitted jaundiced newborns. J Pediatr 2020; 226: 285-8.
[http://dx.doi.org/10.1016/j.jpeds.2020.06.012] [PMID: 32526232]
[49]
Bhatia A, Chua MC, dela Puerta R, Rajadurai VS. Noninvasive detection of hemolysis with ETCOc measurement in neonates at risk for significant hyperbilirubinemia. Neonatology 2020; 117(5): 612-8.
[http://dx.doi.org/10.1159/000509405] [PMID: 32894848]
[50]
Du L, Ma X, Shen X, Bao Y, Chen L, Bhutani VK. Neonatal hyperbilirubinemia management: Clinical assessment of bilirubin production. Semin Perinatol 2021; 45(1), 151351.
[http://dx.doi.org/10.1016/j.semperi.2020.151351] [PMID: 33308896]
[51]
Pakdeeto S, Christensen TR, Bahr TM, et al. Reference intervals for end-tidal carbon monoxide of preterm neonates. J Perinatol 2022; 42(1): 116-20.
[http://dx.doi.org/10.1038/s41372-021-01207-2] [PMID: 34556800]
[52]
Bahr TM, Shakib JH, Stipelman CH, et al. Improving the bilirubin management program in the newborn nursery: Background, aims, and protocol. Neonatology 2020; 117(3): 358-64.
[http://dx.doi.org/10.1159/000505818] [PMID: 32036378]
[53]
Bahr TM, Henry E, Christensen RD, Minton SD, Bhutani VK. A new hour-specific serum bilirubin nomogram for neonates ≥35 weeks of gestation. J Pediatr 2021; 236: 28-33.e1.
[http://dx.doi.org/10.1016/j.jpeds.2021.05.039] [PMID: 34023346]
[54]
Bahr TM, Shakib JH, Stipelman CH, Kawamoto K, Lauer S, Christensen RD. Improvement initiative: End-tidal carbon monoxide measurement in newborns receiving phototherapy. J Pediatrm 2021; 11 S0022-3476(21): 00673-9.
[http://dx.doi.org/10.1016/j.jpeds.2021.07.008]
[55]
Omote V, Ukwamedua HA, Bini N, Kashibu E, Ubandoma JR, Ranyang A. Prevalence, severity, and correlates of anaemia in pregnancy among antenatal attendees in Warri, South-Southern Nigeria: A cross-sectional and hospital-based study. Anemia 2020; 2020(8): 1-7.
[http://dx.doi.org/10.1155/2020/1915231] [PMID: 32455008]
[56]
Kalaivani K. Prevalence & consequences of anaemia in pregnancy. Indian J Med Res 2009; 130(5): 627-33.
[PMID: 20090119]
[57]
Mohan S, Halle-Ekane G, Konje JC. Intestinal parasitic infections in pregnancy – A review. Eur J Obstet Gynecol Reprod Biol 2020; 254: 59-63.
[http://dx.doi.org/10.1016/j.ejogrb.2020.09.007] [PMID: 32942076]
[58]
Ganesh B, Rajakumar T, Acharya SK, Kaur H. Sickle cell anemia/sickle cell disease and pregnancy outcomes among ethnic tribes in India: An integrative mini-review. J Matern Fetal Neonatal Med 2021; 2021, 1872536.
[http://dx.doi.org/10.1080/14767058.2021.1872536] [PMID: 33563075]
[59]
Mohamed S, Sivarajah K, Chakravarti S. A case of severe pyruvate kinase deficiency in a primigravida: Successful outcome. Obstet Med 2013; 6(2): 90-1.
[http://dx.doi.org/10.1258/om.2012.120019] [PMID: 27757165]
[60]
Maberry MC, Mason RA, Cunningham FG, Pritchard JA. Pregnancy complicated by hereditary spherocytosis. Obstet Gynecol 1992; 79(5): 735-8.
[61]
Lal A, Patterson L, Goldrich A, Marsh A. Point-of-care end-tidal carbon monoxide reflects severity of hemolysis in sickle cell anemia. Pediatr Blood Cancer 2015; 62(5): 912-4.
[http://dx.doi.org/10.1002/pbc.25447] [PMID: 25683629]
[62]
Hershko C, Berrebi A, Resnitzky P, Eldor A. Relapsing haemolytic anaemia of pregnancy with negative antiglobulin reaction. Scand J Haematol 1976; 16(2): 135-40.
[http://dx.doi.org/10.1111/j.1600-0609.1976.tb01128.x] [PMID: 1257699]
[63]
Dominico SA, Janmohamed M, Magesa A, et al. Coombs negative hemolytic anemia of unknown origin in pregnancy. J Blood Lymph 2012; 2(2): 103.
[http://dx.doi.org/10.4172/2165-7831.1000103]
[64]
Gupta M, Kala M, Kumar S, Singh G, Chhabra S, Sen R. Idiopathic hemolytic anemia of pregnancy: A diagnostic dilemma. J Hematol (Brossard) 2014; 3(4): 118-20.
[http://dx.doi.org/10.14740/jh171w]
[65]
Lieberman L, Callum J, Cohen R, et al. Impact of red blood cell alloimmunization on fetal and neonatal outcomes: A single center cohort study. Transfusion 2020; 60(11): 2537-46.
[http://dx.doi.org/10.1111/trf.16061] [PMID: 32893897]
[66]
Maisels MJ, Kring E. The contribution of hemolysis to early jaundice in normal newborns. Pediatrics 2006; 118(1): 276-9.
[http://dx.doi.org/10.1542/peds.2005-3042] [PMID: 16818575]
[67]
Watchko JF. Bilirubin-induced neurotoxicity in the preterm neonate. Clin Perinatol 2016; 43(2): 297-311.
[http://dx.doi.org/10.1016/j.clp.2016.01.007] [PMID: 27235209]
[68]
Okumura A, Ichimura S, Hayakawa M, et al. Neonatal jaundice in preterm infants with bilirubin encephalopathy. Neonatology 2021; 118(3): 301-9.
[http://dx.doi.org/10.1159/000513785] [PMID: 33744898]
[69]
Hansen TWR, Maisels MJ, Ebbesen F, et al. Sixty years of phototherapy for neonatal jaundice – from serendipitous observation to stand-ardized treatment and rescue for millions. J Perinatol 2020; 40(2): 180-93.
[http://dx.doi.org/10.1038/s41372-019-0439-1] [PMID: 31420582]
[70]
American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114(1): 297-316.
[http://dx.doi.org/10.1542/peds.114.1.297] [PMID: 15231951]
[71]
Subspecialty Group of Neonatology, The Society of Pediatrics, Chinese Medical Association The experts consensus on the management of neonatal hyperbilirubinemia. Zhonghua Er Ke Za Zhi 2014; 52(10): 745-8.
[PMID: 25537539]

Rights & Permissions Print Cite
Article Metrics
56
2
Wayfinder Image
World Prematurity Day
© 2024 Bentham Science Publishers | Privacy Policy