Kernicterus and the blood-brain-barrier (BBB)
Lou et al. (1977) addressed what appeared to be
the primary concern over "delayed" cord clamping
allowing placental transfusion [1]. Citing the paper
by Lucey et al. (1964) [2] they stated:
"Asphyxiated infants are especially susceptible
to kernicterus, even if their plasma-bilirubin
levels are low.’ Furthermore, it is very difficult to
produce clinical and pathological signs of
kernicterus by injection of bilirubin intravenously
in normal infant monkeys, while kernicterus was
readily produced in previously asphyxiated
monkeys." [1, p1062]
Mossakowski et al. (1968) used Evans blue dye to
investigate the blood-brain barrier in newborn
monkeys subjected to asphyxia by clamping the
umbilical cord and obstructing the airway [3]. Lou et
al. also used Evans blue dye in fetal lambs subjected
to oxygen insufficiency for 1-2 hours:
"The fetuses were asphyxiated by partially
inflating a cuff around the umbilical cord.
Asphyxia developed over a period of 1-2 h (pH
about 690)." [1, p1062]
The initial response of the fetal lambs was a slowing
of heart rate and increased blood pressure during
the first half- to one-hour period of umbilical cord
blood flow restriction. After that the blood pressure
declined and remained low. Twinning is frequent in
lambs, and Lou et al. used the twin as a control for
the fate of Evans blue dye, and reported:
"We have found, in experimental asphyxia
lasting 1-2 h, a striking discoloration throughout
cortex and basal ganglia after intravenous
injection of 3 ml/kg of a 2% solution of Evans
blue in eight non-exteriorised fetal lambs, in
contrast to the uncoloured brain tissue in non-
asphyxiated twins acting as controls." [1, p1062]
In conclusion they commented:
"We suggest that the breakdown of the fetal
blood/brain barrier to albumin is due to a
combination of the initial moderate hypertension
and severe vasodilation during asphyxia.7 The
permeability of the blood/brain barrier to
albumin in asphyxiated babies would facilitate
the transport of bilirubin from plasma to
neurones and thus explain the increased
susceptibility to kernicterus." [1, p1063]
If a baby does not breathe right away at birth, should
the umbilical cord be clamped off right away?
Respiratory depression in infants born alive is a
current concern and topic for research [4, 5]. If an
infant is born alive, it has been receiving oxygen
through the umbilical cord up to the time of birth.
Shouldn't that lifeline be left intact until the lungs
become functional?
Breakdown of the blood brain barrier by asphyxia
has been shown to allow bilirubin and other
substances in the circulation to enter the brain. High
levels of bilirubin won't affect the brain if the blood-
brain barrier has not been breached. Immediate
clamping has been too long defended as a means to
avoid circulatory overload and hyperbilirubinemia.
Lou et al. (1979) reported results of more research
on the vulnerability of the blood-brain barrier to
circulatory insufficiency in fetal lambs [6].
(in progress)
- Lou HC et al. (1977)
Breakdown of blood/brain
barrier in kernicterus.
- Lucey JF et al. (1964)
Kernicterus in asphyxiated
newborn monkeys.
- Mossakowski MJ et al.
(1968) The early
histochemical and
ultrastructural changes in
perinatal asphyxia.
- Baskett TF et al. (2006)
Predictors of respiratory
depression at birth in the
term infant.
- Milsom I et al. (2002)
Influence of maternal,
obstetric and fetal risk
factors on the prevalence of
birth asphyxia at term in a
Swedish urban population.
- Lou HC et al. (1979)
Pressure passive cerebral
blood flow and breakdown of
the blood-brain barrier in
experimental fetal asphyxia.
- Lou HC, Tweed WA, Johnson G, Jones M, Lassen NA. Breakdown of
blood/brain barrier in kernicterus. Lancet. 1977 May 14;1(8020):1062-3.
- Lucey JF, Hibbard E, Behrman RE, Esquival FO, Windle WF. Kernicterus in
asphyxiated newborn monkeys. Exp Neurol 1964 Jan; 9(1):43-58.
- Mossakowski MJ, Long DM, Myers RE, DeCuret HR, Klatzo I. The early
histochemical and ultrastructural changes in perinatal asphyxia. J
Neuropathol Exp Neurol. 1968 Jul;27(3):500-516.
- Baskett TF, Allen VM, O'Connell CM, Allen AC. Predictors of respiratory
depression at birth in the term infant. BJOG. 2006 Jul;113(7):769-74.
- Milsom I, Ladfors L, Thiringer K, Niklasson A, Odeback A, Thornberg E.
Influence of maternal, obstetric and fetal risk factors on the prevalence of
birth asphyxia at term in a Swedish urban population. Acta Obstet Gynecol
Scand. 2002 Oct;81(10):909-17
- Lou HC, Lassen NA, Tweed WA, Johnson G, Jones M, Palahniuk RJ.
Pressure passive cerebral blood flow and breakdown of the blood-brain
barrier in experimental fetal asphyxia. Acta Paediatr Scand. 1979 Jan;68(1):
57-63.