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SPECIAL ARTICLES: Lillian R. Blackmon, Avroy A. Fanaroff, and Tonse N. K. Raju Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: National Institute of Child Health and Human Development Conference Executive Summary Pediatrics 2004; 114: 229-233 [Abstract] [Full text] [PDF]

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Is Bilirubin the Real Cause of Kernicterus?

Eileen Nicole Simon, PhD, RN   (9 December 2004)

Is Bilirubin the Real Cause of Kernicterus? 9 December 2004
Eileen Nicole Simon, PhD, RN, Nursing ConradSimon.org/ 11 Hayes Avenue, Lexington, MA 02420-3521 Send letter to journal: Re: Is Bilirubin the Real Cause of Kernicterus? eileen4brainresearch{at}yahoo.com Eileen Nicole Simon, PhD, RN	I noticed the article by Blackmon et al. on prevention of bilirubin- induced brain injury [1] while looking for something else – McDonagh's letter "Bilirubin the Beneficent" [2]. I hope it is not too late to initiate discussion with Dr. Blackmon and her colleagues on whether bilirubin is the real cause of the brain damage in kernicterus. I think the major emphasis should be on factors that make subcortical nuclei vulnerable to bilirubin staining. If the blood-brain-barrier is intact, many toxic substances like bilirubin should be prevented from getting into neurons. Bilirubin levels are normally high in newborn infants until maturation of liver enzymes that can remove it. The blood- brain-barrier, unless compromised, is the natural defense that must have evolved long ago as a protection against high neonatal bilirubin levels. Bilirubin staining is not uniform in the brain, but affects the same subcortical nuclei that are vulnerable when any lapse in respiration occurs at birth [3, 4, 5]. In their first publication on brain damage in the monkey by asphyxia neonatorum, Rank and Windle made the comment , "The human neuropathologic entity most closely resembling the effects of asphyxia neonatorum in the monkey is kernicterus," [6, p153]. Lucey et al. determined that bilirubin staining in the brain was found only in infant monkeys subjected to asphyxia [5]. Before the cause of erythroblastosis fetalis was known, Zimmerman and Yannet in 1933 summarized a large number of case reports and concluded that kernicterus was caused by bilirubin staining of subcortical nuclei already injured by sepsis or oxygen deprivation. They further commented, "This differs in no way from the well known fact that any intravital dye will localize in zones of injury and will leave unstained tissues which are not damaged," [7, p757]. The earliest descriptions of brain damage in kernicterus are in German (from 1875), and among the summaries in Zimmerman and Yannet's paper; and all emphasized that bilirubin staining was secondary to factors like anoxia that produced necrotic lesions in the brain. As for erythroblastosis fetalis, leakage of blood between infant and mother should not occur if the maternal-infant barrier of the placenta is intact. The human invention of clamping the umbilical cord at birth increases blood pressure in the placenta causing small hemorrhages in the placenta that allow passage of the infant's blood into the mother's circulation with subsequent formation of maternal antibodies that can likewise leak across the placenta in subsequent pregnancies [8]. That kernicterus has re-emerged over the past 15 years corresponds with adoption of immediate clamping of the umbilical cord as a standard obstetric protocol [9]. If clamped before the first breath, the natural shift of placental blood to the lungs will not take place [10]. Experimental asphyxia was accomplished in newborn monkeys by clamping the umbilical cord and not allowing the infant monkey to breathe [3, 4]. Many women have questions and concerns about modern management of childbirth. What we need are more scientific investigations of nature's methods and their evolution in preservation of our species. I hope this inquiry might initiate a discussion on these issues by Blackmon and her colleagues. Eileen Nicole Simon References 1. Blackmon LR, Fanaroff AA, Raju TN; National Institute of Child Health and Human Development. Research on prevention of bilirubin-induced brain injury and kernicterus: National Institute of Child Health and Human Development conference executive summary. 2003. Pediatrics. 2004 Jul;114(1):229-33. 2. McDonagh A. Bilirubin the beneficent. Pediatrics. 2004 Dec;114(6):1741-2. 3. Windle WF. Brain damage by asphyxia at birth. Scientific American, 1969 Oct;221(#4):76-84. 4. Myers RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol. 1972 Jan 15;112(2):246-76. 5. Lucey JF, Hibbard E, Behrman RE, Esquival FO, Windle WF. Kernicterus in asphyxiated newborn monkeys. Experimental Neurology 1964;9:43-58. 6. Ranck JB Jr, Windle WF. Brain damage in the monkey, macaca mulatta, by asphyxia neonatorum. Exp Neurol. 1959 Jun;1(2):130-54. 7. Zimmerman HM and Yannet H. Kernicterus: jaundice of the nuclear masses of the brain. American Journal of Diseases of Children, 1933;45:740-759. 8. Dunn PM. The placental venous pressure during and after the third stage of labour following early cord ligation. J Obstet Gynaecol Br Commonw. 1966 Oct;73(5):747-56. 9. Turrentine JE. Clinical Protocols in Obstetrics and Gynecology, Second Edition. The Parthenon Publishing Group, Boca Raton, London, New York, Washington DC, 2003. 10. Redmond A, Isana S, Ingall D. Relation of onset of respiration to placental transfusion. Lancet. 1965 Feb 6;17:283-5.