http://pediatrics.aappublications.org/cgi/eletters/114/1/229#1214

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?

E-mail 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.