| 26-29 June 2007 - Kernicterus, old and new ideas Bilirubin is considered to be directly toxic to the brain. However, bilirubin staining is not uniform throughout the brain. Subcortical nuclei that control limb and eye movements, and nuclei in the auditory pathway are most prominently affected. The resulting neurological condition is kernicterus. Could autism be a variant of kernicterus? In their first publication on brain damage in the monkey by asphyxia neonatorum, Rank and Windle made the comment:
asphyxia neonatorum in the monkey is kernicterus," [25, p153]. Lucey et al. determined that bilirubin staining in the brain was found only in infant monkeys subjected to asphyxia, and that the nuclei affected by bilirubin were exactly the same ones damaged by asphyxia [22]. The article by Lucey et al. somehow missed being cited in PubMed, and the only fairly recent citation to it is in the article by Wennberg [6]. Wennberg points out:
hypoxic ischemic injury will facilitate transport of bilirubin/albumin into brain..." [7, p97] 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,
localize in zones of injury and will leave unstained tissues which are not damaged," [27, p757]. Kernicterus is best known as the result of erythroblastosis fetalis (or Hemolytic disease of the newborn). See: http://www.nlm.nih.gov/medlineplus/ency/article/001298.htm, and note that now the most common form of maternal-infant incompatibility is ABO incompatibility. Until recently kernicterus was best known as a condition affecting babies born to Rh- negative mothers. After the birth of her first child, placental blood may leak into the mother's bloodstream, and the Rh-negative mother then produces antibodies to this factor if the baby is Rh-positive. In subsequent births maternal antibodies can leak into the baby's blood stream and destroy the baby's red blood cells with resulting high levels of bilirubin. A much heralded treatment for this was devised in the 1960s [15], the now well-known RhoGAM injection given to Rh negative mothers; this replaced the earlier and riskier total replacement of affected infants' blood [8]. A placental barrier prevents mixing of maternal and infant blood throughout pregnancy. Why this barrier should ever break down during birth of the baby merits fuller investigation. 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 mothers circulation with subsequent formation of maternal antibodies that can likewise leak across the placenta in subsequent pregnancies [20]. 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 [4]. References (most recent to oldest):
e-Letters I have written: http://pediatrics.aappublications.org/cgi/eletters/114/1/229 In response to an article by Blackmon et al. on prevention of bilirubin-induced brain injury in newborn infants. http://fn.bmj.com/cgi/eletters/89/2/F101 In response to an article by Murray & Roberts on risks of blood transfusions for newborn infants. The standard practice of clamping the umbilical cord, to prevent hyperbilirubinemia, then often creates a subsequent need for transfusion. http://neoreviews.aappublications.org/cgi/eletters/5/4/e142 In response to an article by Philip & Saigal recommending "wait a minute" before clamping the umbilical cord. Saigal was one of the authors of a paper reporting placental transfusion as cause of hyperbilirubinemia in premature infants [16]. Google:bilirubin levels in newborns http://www.labtestsonline.org/understanding/analytes/bilirubin/test.html
days old. This is sometimes called physiologic jaundice of the newborn. Within the first 24 hours of life, up to 50% of full-term newborns, and an even greater percentage of pre-term babies, may have a high bilirubin level. This is because at birth, the newborn’s liver is not fully mature and lacks the ability to process bilirubin as well as normal. This situation usually resolves itself within a few days. In other instances, newborns’ red blood cells (RBCs) may have been destroyed because of blood incompatibilities between the baby and its mother, called hemolytic disease of the newborn. http://www.kidshealth.org/parent/pregnancy_newborn/common/jaundice.html Updated and reviewed by: Steven Dowshen, MD Date reviewed: April 2005 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5023a4.htm Google: kernicterus bilirubin http://www.neuropathologyweb.org/chapter3/chapter3dBilirubinencephalopathy.html Google: kernicterus symptoms http://www.emedicine.com/ped/topic1247.htm |