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CNS Abnormalities After Neonatal Hemolytic Disease or Hyperbilirubinemia:  A Prospective Study of 405 Patients FREE

Carol B. Hyman, MD; Jacqueline Keaster, MS; Virgil Hanson, MD; Irwin Harris, MD; Robert Sedgwick, MD; Helmut Wursten, PhD
[+] Author Affiliations

Received for publication April 27, 1968.

Reprint requests to 4650 Sunset Blvd, Los Angeles 90027 (Dr. Hyman).


Am J Dis Child. 1969;117(4):395-405. doi:10.1001/archpedi.1969.02100030397002.
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THE etiologic relationship of neonatal bilirubin exposure to classic kernicterus (athetosis, sensori-neural hearing loss, and defective ocular supraversion) is well known, but the relationship to other manifestations of central nervous system (CNS) dysfunction has not been well documented.1-4 The possible interrelationship of neonatal bilirubin exposure and other neonatal factors, such as maturity, hypoxia, and acidosis on the later occurrence of CNS abnormalities, has not been clearly established.5-10

At the Childrens Hospital of Los Angeles, a study of infants with hemolytic disease of the newborn or neonatal hyperbilirubinemia was undertaken to describe all CNS related abnormalities which were detected during at least the four years thereafter. In addition to bilirubin exposure, those other neonatal factors which may have had an influence on the CNS were also documented. The observations provided an opportunity for analyzing the above relationships and for providing the clinician with data which might be useful in

REFERENCES

Koch, C.A.:  Hyperbilirubinemia in Premature Infants: A Follow-up Study II , J Pediat 65:1-11 ( (July) ) 1964;.
Johnston, W.H., et al:  Erythroblastosis Fetalis and Hyperbilirubinemia: A Five-Year Follow-up With Neurological, Psychological, and Audiological Evaluation , Pediatrics 39:88-92 ( (Jan) ) 1967;.
Ose, T., et al:  Follow-up Study of Exchange Transfusion for Hyperbilirubinemia in Infants in Japan , Pediatrics 40:196-201 ( (Aug) ) 1967;.
Vernon, M.:  Rh Factor and Deafness: The Problem, Its Psychological, Physical and Educational Manifestations , Exceptional Child 34:5-12 ( (Sept) ) 1967;.
Freedman, A.M., et al:  The Influence of Hyperbilirubinemia on the Early Development of the Premature , Psychiat Res Rep Amer Psychiat Assoc 13:108-123 ( (Dec) ) 1960;.
Bjure, J., et al:  A Follow-up Study of Hyperbilirubinemia in Full-Term Infants Without Isoimmunisation , Acta Paediat 50:437-443 ( (Sept) ) 1961;.
Killander, A., et al:  Hyperbilirubinemia in Full-Term Newborn Infants: A Follow-up Study , Acta Paediat 52:481-484 ( (Sept) ) 1963;.
Wishingrad, L., et al:  Studies of Non-Hemolytic Hyperbilirubinemia in Premature Infants: I. Prospective Randomized Selection for Exchange Transfusion With Observations on the Levels of Serum Bilirubin With and Without Exchange Transfusion and Neurologic Evaluations One Year After Birth , Pediatrics 36:162-172 ( (Aug) ) 1965;.
Boggs, T.R., Jr.; Hardy, J.B.; and Frazier, T.M.:  Correlation of Neonatal Serum Total Bilirubin Concentrations and Developmental Status at Age Eight Months: A Preliminary Report From the Collaborative Project , J Pediat 71:553-560 ( (Oct) ) 1967;.
Holmes, G.E.; Miller, J.B.; and Smith, E.E.:  Neonatal Bilirubinemia in Production of Long-Term Neurological Deficits , Amer J Dis Child 116: 37-43 ( (July) ) 1968;.
Malloy, H.T., and Evelyn, K.A.:  Determination of Bilirubin With Photoelectric Colorimeter , J Biol Chem 119:480 ( (July) ) 1937;.
Kaplan, S.A.; Yuceoglu, A.M.; and Strauss, J.:  Chemical Microanalysis: Analysis of Capillary and Venous Blood , Pediatrics 24:270-274 ( (Aug) ) 1959;.
Lucey, J.F., et al:  A Difference in the Incidence of Hyperbilirubinemia Among Premature Infants in Two Hospitals , Pediatrics 30:3-11 ( (July) ) 1962;.
Mollison, P.L.: Blood Transfusion in Clinical Medicine , ed 2, Oxford, England: B. H. Blackwell, Ltd., 1956;, pp 585-587.
The Clinical Chemist:  Recommendation on a Uniform Bilirubin Standard , Clin Chem 8:405-407, 1962;.
Gesell, A., and Amatruda, C.A.: Developmental Diagnosis , ed 2, New York: Paul B. Hoeber, Inc., Medical Book Department of Harper & Row, 1954;, p 15.
Keaster, J.; Hyman, C.B.; and Harris, I.:  Hearing Problems Subsequent to Neonatal Hemolytic Disease or Hyperbilirubinemia , Amer J Dis Child 117:406-410 ( (April) ) 1969;.
Rapin, I.: " Brain Damage in Children ," in Brenneman, J., and Kelley, V.C. (eds.): Practice in Pediatrics , Hagerstown, Md.: W. F. Prior Co., Inc., 1966;, vol 4, p 1.
Work, H.H., and Haldane, J.E.:  Cerebral Dysfunction in Children , Amer J Dis Child 111:573-580 ( (June) ) 1966;.
MacKeith, R., and Bax, M. (eds.): Minimal Cerebral Dysfunction , London: William Heinemann, Ltd., 1963;.
Santostefano, S.:  Psychologic Testing in Evaluating and Understanding Organic Brain Damage and the Effects of Drugs in Children , J Pediat 62: 766-781 ( (May) ) 1963;.
Odell, G.B.:  The Dissociation of Bilirubin From Albumin and Its Clinical Implications , J Pediat 55:268-279 ( (Sept) ) 1959;.
Odell, G.B.: " Factors Influencing the Binding of Bilirubin by Albumin ," in A. Sass-Kortsak (ed.), Kernicterus , Canada: University of Toronto Press, 1961;, pp 199-207.
Johnson, L.M.: " The Effect of Certain Substances on Bilirubin Levels and Occurrence of Kernicterus in Genetically Jaundiced Rats ," in A. Sass-Kortsak (ed.), Kernicterus , Canada: University of Toronto Press, 1961;, pp 208-218.
Jones, M.H., et al:  Longitudinal Study of the Incidence of Central Nervous System Damage Following Erythroblastosis Fetalis , Pediatrics 14: 346-350 ( (Oct) ) 1954;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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References

Koch, C.A.:  Hyperbilirubinemia in Premature Infants: A Follow-up Study II , J Pediat 65:1-11 ( (July) ) 1964;.
Johnston, W.H., et al:  Erythroblastosis Fetalis and Hyperbilirubinemia: A Five-Year Follow-up With Neurological, Psychological, and Audiological Evaluation , Pediatrics 39:88-92 ( (Jan) ) 1967;.
Ose, T., et al:  Follow-up Study of Exchange Transfusion for Hyperbilirubinemia in Infants in Japan , Pediatrics 40:196-201 ( (Aug) ) 1967;.
Vernon, M.:  Rh Factor and Deafness: The Problem, Its Psychological, Physical and Educational Manifestations , Exceptional Child 34:5-12 ( (Sept) ) 1967;.
Freedman, A.M., et al:  The Influence of Hyperbilirubinemia on the Early Development of the Premature , Psychiat Res Rep Amer Psychiat Assoc 13:108-123 ( (Dec) ) 1960;.
Bjure, J., et al:  A Follow-up Study of Hyperbilirubinemia in Full-Term Infants Without Isoimmunisation , Acta Paediat 50:437-443 ( (Sept) ) 1961;.
Killander, A., et al:  Hyperbilirubinemia in Full-Term Newborn Infants: A Follow-up Study , Acta Paediat 52:481-484 ( (Sept) ) 1963;.
Wishingrad, L., et al:  Studies of Non-Hemolytic Hyperbilirubinemia in Premature Infants: I. Prospective Randomized Selection for Exchange Transfusion With Observations on the Levels of Serum Bilirubin With and Without Exchange Transfusion and Neurologic Evaluations One Year After Birth , Pediatrics 36:162-172 ( (Aug) ) 1965;.
Boggs, T.R., Jr.; Hardy, J.B.; and Frazier, T.M.:  Correlation of Neonatal Serum Total Bilirubin Concentrations and Developmental Status at Age Eight Months: A Preliminary Report From the Collaborative Project , J Pediat 71:553-560 ( (Oct) ) 1967;.
Holmes, G.E.; Miller, J.B.; and Smith, E.E.:  Neonatal Bilirubinemia in Production of Long-Term Neurological Deficits , Amer J Dis Child 116: 37-43 ( (July) ) 1968;.
Malloy, H.T., and Evelyn, K.A.:  Determination of Bilirubin With Photoelectric Colorimeter , J Biol Chem 119:480 ( (July) ) 1937;.
Kaplan, S.A.; Yuceoglu, A.M.; and Strauss, J.:  Chemical Microanalysis: Analysis of Capillary and Venous Blood , Pediatrics 24:270-274 ( (Aug) ) 1959;.
Lucey, J.F., et al:  A Difference in the Incidence of Hyperbilirubinemia Among Premature Infants in Two Hospitals , Pediatrics 30:3-11 ( (July) ) 1962;.
Mollison, P.L.: Blood Transfusion in Clinical Medicine , ed 2, Oxford, England: B. H. Blackwell, Ltd., 1956;, pp 585-587.
The Clinical Chemist:  Recommendation on a Uniform Bilirubin Standard , Clin Chem 8:405-407, 1962;.
Gesell, A., and Amatruda, C.A.: Developmental Diagnosis , ed 2, New York: Paul B. Hoeber, Inc., Medical Book Department of Harper & Row, 1954;, p 15.
Keaster, J.; Hyman, C.B.; and Harris, I.:  Hearing Problems Subsequent to Neonatal Hemolytic Disease or Hyperbilirubinemia , Amer J Dis Child 117:406-410 ( (April) ) 1969;.
Rapin, I.: " Brain Damage in Children ," in Brenneman, J., and Kelley, V.C. (eds.): Practice in Pediatrics , Hagerstown, Md.: W. F. Prior Co., Inc., 1966;, vol 4, p 1.
Work, H.H., and Haldane, J.E.:  Cerebral Dysfunction in Children , Amer J Dis Child 111:573-580 ( (June) ) 1966;.
MacKeith, R., and Bax, M. (eds.): Minimal Cerebral Dysfunction , London: William Heinemann, Ltd., 1963;.
Santostefano, S.:  Psychologic Testing in Evaluating and Understanding Organic Brain Damage and the Effects of Drugs in Children , J Pediat 62: 766-781 ( (May) ) 1963;.
Odell, G.B.:  The Dissociation of Bilirubin From Albumin and Its Clinical Implications , J Pediat 55:268-279 ( (Sept) ) 1959;.
Odell, G.B.: " Factors Influencing the Binding of Bilirubin by Albumin ," in A. Sass-Kortsak (ed.), Kernicterus , Canada: University of Toronto Press, 1961;, pp 199-207.
Johnson, L.M.: " The Effect of Certain Substances on Bilirubin Levels and Occurrence of Kernicterus in Genetically Jaundiced Rats ," in A. Sass-Kortsak (ed.), Kernicterus , Canada: University of Toronto Press, 1961;, pp 208-218.
Jones, M.H., et al:  Longitudinal Study of the Incidence of Central Nervous System Damage Following Erythroblastosis Fetalis , Pediatrics 14: 346-350 ( (Oct) ) 1954;.

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