Kernicterus, a preventable injury to the brain due to severe neonatal jaundice, has re-emerged in the United States as a health and societal concern. In its usually recognized form, kernicterus causes devastating disabilities, including athetoid cerebral palsy and speech and hearing impairments. In response to disturbing reports of kernicterus in term and near-term infants discharged as “healthy” from their place of birth, A. K. Brown and colleagues inaugurated a Pilot Kernicterus Registry in May, 1992 at the 10th Annual Kernicterus Symposium. Drs. Lois Johnson and Audrey Brown maintained a confidential manual database of acute and chronic bilirubin encephalopathies for voluntary reporting of cases of kernicterus (considered by many to be an “underground” disease). Usually referring to the icteric (yellow) staining of the basal ganglia and lesions of the extrapyramidal nervous system, kernicterus is detected at autopsy. Now, the Pilot Kernicterus Registry has offered formal clinical definitions of bilirubin-induced neurologic dysfunction (BIND) and kernicterus. (1)
Audrey K. Brown, the “grande dame of bilirubin,” helped us to understand bilirubin conjugation and to respect the dangers of excessive total serum bilirubin (TSB) load. She was a leader in the campaign to prevent kernicterus. Her historical review (see accompanying special article) chronicles the achievements of the researchers of kernicterus. Her research reminds us of the universality of neonatal bilirubinemia. Sadly, she also chronicled both the fall and rise of kernicterus. Dr. Brown and other “ancestral” researchers imparted a legacy to maintain vigilance for the perpetual and ominous specter of kernicterus that can threaten humanity now and for generations to come. The current re-emergence of kernicterus in babies discharged as healthy from United States hospitals represents a crisis of pediatrician credibility, a societal demand for patient safety, and a disease that needs to be controlled by public health policy.
Incidence of Kernicterus
The actual incidence of kernicterus in the United States is difficult to document and measure because there are no formal processes for reporting or documenting kernicterus. The numbers reported to the Registry must be an underestimate of the actual incidence (Figure). To date, 125 term and near-term newborns have been registered from more than 34 states and two United States Army camps in Germany. Recent reports from Canada, Denmark, Great Britain, Australia, and New Zealand provide a global dimension to this re-emergence. More cases continue to be reported to the registry. The incidence of severe hyperbilirubinemia (>95th percentile for age in hours on the hour-specific bilirubin nomogram) (2) and “dangerous” hyperbilirubinemia, with TSB values greater than 25 mg/dL (427.5 mcmol/L) (>99.9th percentile) in seemingly healthy near-term and term babies can provide surrogate indices of risk for kernicterus. The incidence of babies who may develop “dangerous” level TSB values (≥25 mg/dL [427.5 mcmol/L]) if prompt treatment is not instituted to decrease the systemic bilirubin load rapidly has been reported in two observational studies and ranges from 0.14% to 0.16%. (3)(4) In an era when phototherapy was not available, the Collaborative Perinatal Project (1959 through 1966) studied 41,324 well babies treated with exchange transfusions. Transfusions were administered to 30% of the babies who had TSB levels of at least 20 mg/dL (342 mcmol/L), 83% who had TSB levels of at least 25 mg/dL (427.5 mcmol/L), and 100% who had TSB levels of at least 30 mg/dL (513 mcmol/L). The investigators identified 66 babies who had TSB levels greater than 25 mg/dL (427.5 mcmol/L), an incidence of 0.16% or 1 per 625 well babies. More recently, Newman and associates (3) identified 73 babies who had TSB values greater than 25 mg/dL (427.5 mcmol/L) among 51,387 well babies cared for in the Kaiser Permanente system in California, an incidence of 0.14% or 1 per 700 well babies, who were treated with phototherapy (generally in accordance with American Academy of Pediatrics [AAP] guidelines). Based on these data, (2)(3)(4) we can estimate that 1 in 80 babies who has severe hyperbilirubinemia (>95th percentile) or 1 in 650 well newborns could develop “dangerous” hyperbilirubinemia and be at significant or immense risk for kernicterus if there are no fail-safe, system-based protocols.
The scope of the burden on society of kernicterus may be defined by the magnitude of “significant” and “injurious” hyperbilirubinemia in 3.5 million well babies (among an annual United States birth total of 4 million babies) who needed invasive interventions. (5) Based on the current health care system with random or ad hoc evaluation or intervention strategies, in 1997 (Health Care Utilization Project database), as many as 112,000 well babies received phototherapy (∼3.2% of the well baby population) and as many as 1,785 newborns needed exchange transfusion (∼0.05% of well babies). These babies would have been at risk for neurologic injury if the interventions were not timely or efficacious. Kernicterus not only ranks among the highest cost per new case (Centers for Disease Control and Prevention Financial Burden of Disability Study, 1992), but also results in profound and uncompromising grief for the family and loss to siblings of healthy, talkative playmates. For the child who has kernicterus (usually remarkably intelligent, but trapped in an uncontrollable body), grief and frustration are enormous.
All healthy infants are at potential risk of kernicterus if their newborn jaundice is unmonitored and treated inadequately. This has been evidenced by the Pilot Kernicterus Registry database and attributed to interacting phenomena of: 1) early hospital discharge (before extent of jaundice is known and signs of impending brain damage have appeared), 2) lack of adequate concern for the risks of severe jaundice in healthy term and near-term newborns, 3) an increase in breastfeeding without appropriate lactational counseling to ensure adequate intake, 4) medical care cost constraints, 5) paucity of educational materials to enable parents to participate in safeguarding their newborns, and 6) structural limitations within the health care system. These lapses in care and root causes serve as the empiric evidence for a model to implement a family-centered, system-based approach that builds constructive parent/health care partnerships to prevent acute kernicterus and the clinical spectrum of BIND due to adverse outcomes of neonatal hyperbilirubinemia. (1)
Building “Health and Society” Partnerships
A group of parents consented to have video clips and case histories of their children compiled into the “BIND video documentary” prepared at Pennsylvania Hospital in the summer of 2000. One of the mothers, Sue Sheridan, had been invited to testify at the President’s Summit Meeting on Medical Errors in September, 2000. Joined by other families, these parents were invited to the first screening of the documentary at an AAP satellite meeting in Chicago in October, 2000. A confluence of events and far-sighted visions occurred when the parents met as a group and with concerned physicians for the first time. The families decided to form a support and advocacy group (Parents of Infants and Children with Kernicterus [PICK]). Along with the physicians (who subsequently constituted their advisory board), they chose to build a foundation for “health and society” partnerships.
The proposed revision of the 1994 AAP practice parameters for newborn jaundice galvanized the medical advisory board and PICK to conceive and conduct a unique gathering of parents, medical experts on neonatal jaundice and kernicterus, representatives of health care regulatory agencies, and pediatric and nursing professional organizations at Pennsylvania Hospital in February, 2001. The objective for this full-day meeting on “Strategies for a Systemwide Approach in the Management of Hyperbilirubinemia to Prevent Kernicterus” was to develop a framework for a systems-wide change in the pre- and postdischarge management of neonatal jaundice. At the conclusion of the workshop, the meeting participants generally agreed that system-wide awareness and application of strategies would advance the goal of prevention of BIND.*As a follow-up to this meeting, JCAHO, (6) AHRQ, (7) AAP, (8) AWHONN, and CDC (9) reviewed their roles in the prevention of severe hyperbilirubinemia and kernicterus, publishing their results and suggestions for action. The National Quality Forum (AHRQ) has now declared kernicterus as one of the “never events,” the only pediatric condition in this list. The parent-physician partnership has continued to advocate universal bilirubin screening prior to discharge and implementation of a system-based approach to prevent kernicterus. They have also embarked on a Safety and Family Education (S.A.F.E.) program for management of newborn jaundice to define presentinel trigger events that place a newborn at risk for kernicterus; to expand the Pilot Kernicterus Registry to a formal, ongoing national surveillance system; and to prepare a national outreach campaign to achieve a “zero tolerance of kernicterus.”
↵* *Together with their Medical Advisory Board (VK Bhutani, AK Brown, WJ Cashore, LH Johnson, SA Shapiro, DK Stevenson), this informed, articulate, and dedicated parents’ group developed a comprehensive syllabus, which contained statements by the parents, a representative body of pertinent medical literature, and an estimated incidence of hyperbilirubinemia in excess of the 95th percentile. Susan Sheridan arranged for the participation in the meeting of representatives of the Agency for Healthcare Research and Quality (AHRQ), Centers for Disease Control and Prevention (CDC), Healthcare Financing Administration (HCFA), Joint Commission on Accreditation of Healthcare Organizations (JCAHO), Maternal Child Health Bureau (MCH), National Institutes of Health (NIH), and Office of Science Planning. In collaboration with their medical advisory board, PICK also sent invitations to representatives of the American Academy of Pediatrics (AAP, represented by MJ Maisels), Association of Women’s Obstetrical Health and Newborn Nursing (AWOHNN, represented by S. Gennaro), Making Advances Against Jaundice in Infant Care (MAJIC, a joint project of Harvard School of Public Health and the AAP, represented by MH Palmer), National Association of Neonatal Nurses (NANN, represented by A Schwoebel), and the Harvard Life Bridge Program (Boston Children’s Hospital, represented by JJ Volpe and A Duplesis), all of whom agreed to attend.
- Copyright © 2003 by the American Academy of Pediatrics
Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a pre-discharge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999;103:6–14
Newman TB, Klebanoff M. Neonatal hyperbilirubinemia and long-term outcome: another look at the collaborative perinatal project. Pediatrics. 1993;92:651–657
HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD. Available at: www.ahrq.gov/data/hcup/hcupnet.htm
JCAHO Sentinel Event Alert: Kernicterus threatens healthy babies. Available at: http://www.JACHO.org. Issue 18, April 2001
A national framework for healthcare quality measurement and reporting: a consensus report. National Quality Forum. Available at: http://www.qualityforum.org
AAP Subcommittee on Neonatal Hyperbilirubinemia. Neonatal jaundice and kernicterus. Pediatrics. 2001;108:763–765