UNIVERSITY OF CALIFORNIA, LOS ANGELES “ UCLA

 

BERKELEY + DAVIS + IRVINE + LOS ANGELES + RIVERSIDE + SAN DIEGO + SAN FRANCISCO SANTA BARBARA + SANTA CRUZ

 

 

DEPARTMENT OF PSYCHIATRY AND

BIOBEHAVIORAL SCIENCES

December 9 ; 1983 UCLA SCHOOL OF MEDICINE
760 WESTWOOD PLAZA

LOS ANGELES, CALIFORNIA 90024

Dr. Joshua Lederberg
President

Rockefeller University
New York, New York 10021

Dear Dr. Lederberg,

 

Dr. Tarjan asked me to try and respond to your letter
concerning the role of kernicterus in mental retardation.
This is very hard to do, since there are no recent figures
of relevance. The major decrease in kernicterus occurred with
the control of Rhesus incompatibility.

The main group of infants at risk now for kernicterus
are low birth weight infants, A recent review of infant
morbidity (Shapiro, et.al., Pediatrics 72, 408, 1983) found
that 6.11% of infants weighed less than 2500 grams at birth
and 0.98%, or approximately 1/6, weighed less than 1500 grams;
it is this last group that are at greatest risk for kernicterus.

Levine, et.al., (Pediatrics 69, 255, 1982) noted that
hyperbilirubinemia is about the commonest medical diagnosis in
the newborn, particularly in prematures. 5% of liveborn
neonatal autopsies demonstrated kernicterys (Turkel, et.al.,
Pediatrics 69, 267, 1982). If these figures are correct, they
translate into 5% of the 46,000 infant deaths per year (using
4,000,000 as the live birth rate per year in the U.S.), or
2,300. Undoubtedly, other factors contributed to some of
these deaths (congenital abnormalities, intracranial hemorrhage, etc.).

The best that I can do with regard to "outcomes" for infants
weighing €1500 grams follows. However, it does not address the
issue of kernicterus. Between 1975-79, infant mortality rates
decreased for those weighing 1000-1500 grams, and 18% were left
with major neuropsychiatric disabilities (Knoblock, et.al.,
Pediatrics 69, 285, 1982). Shapiro's study quoted above found
that about 6% of infants weighing €1500 grams at birth had
gross motor performance delay (DQ4€70) and a further 17% were
borderline (DQ 70-79) when assessed at 1 year of age.
Dr. Joshua Lederberg
December 9, 1983
Page 2

The predictive value of serum bilirubin levels, free
or total, was poor. Ritter, et.al. (Pediatrics 69, 260, 1982)
studied 91 infants weighing €1500 grams at birth; 58% died and
of these, 23% showed pathologic evidence of kernicterus. There
was no significant difference in either the free or total
bilirubin in infants with and without kernicterus. Further,
hyperbilirubinemia may result from hemorrhage into a closed
Space and recent ultrasound studies indicate that nearly 50%
of infants weighing €1500 grams have intracranial hemorrhage;
this rather than the hyperbilirubinemia may be the cause of
brain damage,

I think I can summarize this data in the following way:

1. Hyperbilirubinemia is common in premature infants,
particularly in those weighing €1500 grams (the incidence
in different reports varies between 2-16%).

26 Serum bilirubin levels appear to be a poor predictor of
kernicterus.

3. Hyperbilirubinemia may result from a number of factors,
including brain hemorrhage.

4. Brain hemorrhage itself may be the cause of subsequent
neurologic impairment, including mental retardation.

5. In addition, primary hyperbilirubinemia almost certainly

contributes to neurologic impairment and mental retardation.
This probably results from changes in the blood-brain
barrier (Levine, et.al., Pediatrics 69, 255, 1982) allowing
bilirubin into the brain.

Your proposed studies would be relevant to this last group.
It would be very difficult to separate the last two. groups, or
to predict the number of cases of mental retardation prevented.

I hope this information will be of help to you. Please
let me know if I can help you further.

With best wishes,

Tdue F brovclatl

Barbara F. Crandall, M.D.
Professor of Pediatrics and Psychiatry
Director, Prenatal Diagnostic Center

BFC:as

cc: George Tarjan, M.D.