Race, Ethnicity, and the Propensity for Neonatal Jaundice Papers presented at the Eighth Annual Kernicterus Symposium Introduction by David K. Stevenson, M.D.* Audrey K. Brown, M.D.**
*
>he
Eighth
Annual
t
Kernicterus Symposium, entitled &dquo;Race, Ethnicity, and the Propensity for Neonatal Jaundice,&dquo; included several presentations that reviewed the propensity for neonatal jaundice in certain racial or ethnic groups widely represented in US communities. Although a variety of alterations in transitional bilirubin metabolism contribute to neonatal jaundice, increased bilirubin production is one of the most important contributing factors in all kinds of neonatal jaundice. The papers selected for presentation here address this and others factors which are related to the clinically observed differences in the risk of jaundice and which prompt treatment of infants in these ethnic groups.
Historically, infants with elevated serum bilirubin concentrations have been treated aggressively to prevent the development of kernicterus. Although there is a widespread belief that healthy term babies may not be at greater risk for mental or physical impairment until serum bilirubin concentrations rise well above 20 mg/dL *
**
706
Department of
Pediatrics Division of Neonatal and Developmental Medicine Stanford University School of Medicine Stanford, California Department of Pediatrics Children’s Medical Center of Brooklyn State University of New York - HSC Brooklyn, New York
(342 pmol/L), that
such
a
it
cannot
be said
risk.
Moreover, belief, supported by meta-
they
are
at
no
analysis of multiple studies spanning decades, certainly cannot be extrapolated to particular ethnic groups and is not totally reassuring with respect to exposures above 20 mg/dL (342 pmol/L) for any individual baby. Also, the factor of duration of exposure has not been addressed by any of the recent
analyses.
While it is not unreasonable to question the aggressive treatment of jaundice in term babies whose jaundice is not caused by hemolysis and who are otherwise well, it should be remembered that term infants without hemolysis, but with a genetic defect in glucuronyl transferase (Crigler-Najjar syndrome), develop kernicterus. For such infants, it is, in fact, important to develop less costly and less stressful diagnostic and treatment regimens for the management of jaundice during the transitional period, remembering that the effects of hyperbilirubinemia in premature infants, infants of different ethnic groups, and those with hemolytic disease may be different from its effects in healthy Caucasian term infants. The identification of increased bilirubin production by the telltale sign of hemolysis thus becomes a major strategic approach to such populations at potentially high risk for developing
jaundice. Normally, approximately
80%
Downloaded from cpj.sagepub.com at Freie Universitaet Berlin on May 9, 2015
to 90% of all bilirubin is produced from the breakdown of heme derived from senescent red cells; under hemolytic conditions, an even greater proportion of bilirubin originates from the turnover of erythroid heme. The two most widely used treatments for exaggerated neonatal hyperbilirubinemia caused by hemolysis are phototherapy and exchange transfusion, therapies which remove bilirubin that has already been produced. However, the suppression of bilirubin formation is a more logical and preventive strategy, particularly when targeted at those individuals found to be at risk because of increased bilirubin production. Several metalloporphyrin analogues of heme have been found to inhibit the activity of heme oxygenase, the rate-limiting enzyme in bilirubin production, and ameliorate neonatal hyperbilirubinemia. To date, the identified inhibitors have included tin, zinc, chromium, and manganese porphyrin complexes. Based on estimates of total bilirubin production, criteria could be formulated that would facilitate early discharge from the hospital and management of transitional hy-
perbilirubinemia
on
an
outpa-
tient basis for those infants at low risk for the development of severe
hyperbilirubinemia (>20 [>342
mg/dL
Jlmol/L]) because they pro-
duce bilirubin at
Using the proaches,
same
a
normal
rate.
technological
apinfants from the well-
baby population who are high producers of the pigment could be identified as being at high risk for the development of severe hyperbilirubinemia, thus targeting them for preventive approaches to therapy. of the ethnic groups in which inborn errors of metabolism, such as glucose-6-phosphate
In
some
dehydrogenase deficiency,
account
for
hemolysis
and
hyperbiliru-
binemia, the risk of kernicterus may be enhanced of
that
by the presence hemolysis. Whether
hemolysis per se enhances the toxicity of a given bilirubin concentration is still unknown but must be taken into account as a possibility. Because the propensity for neonatal jaundice is increased in certain ethnic groups, better def-
inition of its natural history in these groups, ascertaining its ethnic-specific risk of causing injury, and understanding its pathogenesis become of paramount importance in our multi-ethnic society. The papers presented at the Eighth Annual Kernicterus Symposium and published here represent an initial approach to these
important questions.
Downloaded from cpj.sagepub.com at Freie Universitaet Berlin on May 9, 2015
707
*
>he
Eighth
Annual
t
Kernicterus Symposium, entitled &dquo;Race, Ethnicity, and the Propensity for Neonatal Jaundice,&dquo; included several presentations that reviewed the propensity for neonatal jaundice in certain racial or ethnic groups widely represented in US communities. Although a variety of alterations in transitional bilirubin metabolism contribute to neonatal jaundice, increased bilirubin production is one of the most important contributing factors in all kinds of neonatal jaundice. The papers selected for presentation here address this and others factors which are related to the clinically observed differences in the risk of jaundice and which prompt treatment of infants in these ethnic groups.
Historically, infants with elevated serum bilirubin concentrations have been treated aggressively to prevent the development of kernicterus. Although there is a widespread belief that healthy term babies may not be at greater risk for mental or physical impairment until serum bilirubin concentrations rise well above 20 mg/dL *
**
706
Department of
Pediatrics Division of Neonatal and Developmental Medicine Stanford University School of Medicine Stanford, California Department of Pediatrics Children’s Medical Center of Brooklyn State University of New York - HSC Brooklyn, New York
(342 pmol/L), that
such
a
it
cannot
be said
risk.
Moreover, belief, supported by meta-
they
are
at
no
analysis of multiple studies spanning decades, certainly cannot be extrapolated to particular ethnic groups and is not totally reassuring with respect to exposures above 20 mg/dL (342 pmol/L) for any individual baby. Also, the factor of duration of exposure has not been addressed by any of the recent
analyses.
While it is not unreasonable to question the aggressive treatment of jaundice in term babies whose jaundice is not caused by hemolysis and who are otherwise well, it should be remembered that term infants without hemolysis, but with a genetic defect in glucuronyl transferase (Crigler-Najjar syndrome), develop kernicterus. For such infants, it is, in fact, important to develop less costly and less stressful diagnostic and treatment regimens for the management of jaundice during the transitional period, remembering that the effects of hyperbilirubinemia in premature infants, infants of different ethnic groups, and those with hemolytic disease may be different from its effects in healthy Caucasian term infants. The identification of increased bilirubin production by the telltale sign of hemolysis thus becomes a major strategic approach to such populations at potentially high risk for developing
jaundice. Normally, approximately
80%
Downloaded from cpj.sagepub.com at Freie Universitaet Berlin on May 9, 2015
to 90% of all bilirubin is produced from the breakdown of heme derived from senescent red cells; under hemolytic conditions, an even greater proportion of bilirubin originates from the turnover of erythroid heme. The two most widely used treatments for exaggerated neonatal hyperbilirubinemia caused by hemolysis are phototherapy and exchange transfusion, therapies which remove bilirubin that has already been produced. However, the suppression of bilirubin formation is a more logical and preventive strategy, particularly when targeted at those individuals found to be at risk because of increased bilirubin production. Several metalloporphyrin analogues of heme have been found to inhibit the activity of heme oxygenase, the rate-limiting enzyme in bilirubin production, and ameliorate neonatal hyperbilirubinemia. To date, the identified inhibitors have included tin, zinc, chromium, and manganese porphyrin complexes. Based on estimates of total bilirubin production, criteria could be formulated that would facilitate early discharge from the hospital and management of transitional hy-
perbilirubinemia
on
an
outpa-
tient basis for those infants at low risk for the development of severe
hyperbilirubinemia (>20 [>342
mg/dL
Jlmol/L]) because they pro-
duce bilirubin at
Using the proaches,
same
a
normal
rate.
technological
apinfants from the well-
baby population who are high producers of the pigment could be identified as being at high risk for the development of severe hyperbilirubinemia, thus targeting them for preventive approaches to therapy. of the ethnic groups in which inborn errors of metabolism, such as glucose-6-phosphate
In
some
dehydrogenase deficiency,
account
for
hemolysis
and
hyperbiliru-
binemia, the risk of kernicterus may be enhanced of
that
by the presence hemolysis. Whether
hemolysis per se enhances the toxicity of a given bilirubin concentration is still unknown but must be taken into account as a possibility. Because the propensity for neonatal jaundice is increased in certain ethnic groups, better def-
inition of its natural history in these groups, ascertaining its ethnic-specific risk of causing injury, and understanding its pathogenesis become of paramount importance in our multi-ethnic society. The papers presented at the Eighth Annual Kernicterus Symposium and published here represent an initial approach to these
important questions.
Downloaded from cpj.sagepub.com at Freie Universitaet Berlin on May 9, 2015
707
