Reye Syndrome in Children Less than 1 Year Old: Some Epidemiologic Observations

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Figure. Intravenous cannula set used for tympanocentesis after the needle has been bent.

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catarrhalis, and anaerobes. The procedure also pre-vents flushing of the aspirated fluid by air, a phe-nomenon which happens when the commonly used Senturia apparatus is utilized. Using the above technique, we have been able to recover microor-ganisms in 90% of 180 pediatric patients with acute otitis media,t and from 49 patients with chronic otitis media4 without any complication. We isolated anaerobes from 25% of the patients with acute otitis media,t and 56% of those with chronic otitis media,4 thus taking advantage of the limited amount of air which is aspirated using this procedure.


George Washington University Medical School Washington, DC


1. Bluestone CD, Shurini PA: Middle ear disease in children:

Pathogenesis, diagnosis and management. Pediatr Clin North Am 21:379, 1974

2. Brook I: Aspiration of fluid from middle ear. Hosp Phys 14: 42, 1978

3. Brook I: Aerobic and anaerobic bacteriology of acute otitis media in pediatric patients. Clin Proc Child Hosp Nati Med Cent 34:158, 1978

4. Brook I, Finegold SM: Bacteriology of chronic otitis media. JAMA 241:487, 1979



in Children



1 Year





Much of the epidemiology of Reye syndrome is still not well understood, particularly in the age group <1 year of age. Huttenlocher and Trauner’ recently reported the clinical findings in a series of patients <6 months of age. They noted that a disproportionate number of infants came from lower socioeconomic areas.

A 1973 to 1977 epidemiologic study of Reye syn-drome in Ohio by the Ohio State Department of Health and the Center for Disease Control (CDC) has shown different age-specific attack rates for

black children and for white children.2 Although the overall attack rates of Reye syndrome for black and for white children were not significantly differ-ent, among children <1 year old, black children had a rate of Reye syndrome approximately eight times the rate for whites. For most older age groups the attack rates for blacks were less than the attack rates for whites. The present report describes the epidemiologic information on 54 children <1 year old with Reye syndrome reported to CDC from

1974 through April 1978, with particular emphasis on differences between the black and white pa-tients.


Case Definition

A case of Reye syndrome was defined as an acute noninflammatory encephalopathy demonstrated by either cerebrospinal fluid (if available) containing

<8 white blood cells per mm4 or cerebral edema

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2 3 4 5 6 7 8 9 10 II 12


Reye syndrome in 1-year-old children, by race

628 PEDIATRICS Vol. 65 No. 3 March 1980

without perivascular or meningeal inflammation as-sociated with (1) microvesicular fatty metamorpho-sis of the liver diagnosed by biopsy or autopsy, or (2) a greater than threefold rise in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, or serum ammonia, and (3) no other more reasonable explanation for the neurologic or hepatic abnormalities.34

Case Finding

Ohio Data. We contacted all hospitals in Ohio with more than 500 beds or more than 40 pediatric beds. The hospitals were asked to provide medical records of all patients with Reye syndrome with onset of illness prior to December 31, 1977. A wide variety of means were employed to identify records, including case listings kept by referral centers, re-views of related discharge diagnoses, reviews of admission log books, and physician interviews. One of the authors reviewed each patient’s medical rec-ord to determine whether that patient fit the case definition.

National Surveillance Data. Cases are reported to the CDC on standard case investigation forms by state and territorial epidemiologists, hospitals, and private physicians. The report forms contain information on basic demographics, prodromal ill-ness, laboratory findings, treatment, outcome, and method of diagnosis. These report forms are re-viewed by CDC personnel to determine whether the report in fact meets the case definition. The records of all children <1 year old with suspected Reye syndrome reported to CDC from 1974 through April 1978 and the records of all children <1 year old with Reye syndrome found by the Ohio study were reviewed.


Fifty-four children were studied for this report:

16 children from the Ohio study, the rest from CDC records. Fifteen (58%) black children and 16 (57%) white children had histologic confirmation of the diagnosis of Reye syndrome (P > .05). Forty-eight percent of the children were black and 52% were white. Excluding the cases from Ohio did not sig-nificantly alter the racial distribution. Of all cases >1 year old reported to CDC and found through the Ohio Study, 92% were white and 8% were black. These ratios are significantly different (P < .001).

Of the children with known antecedent illness, 32 (72%) had an antecedent illness that was character-ized as primarily respiratory, 6 (14%) had an illness that was primarily gastrointestinal, and 2 (5%) had fever alone. The remainder of children had a variety of signs and symptoms including one case of urinary tract infection, one case of varicella, and two cases

of nonvaricella exanthem. One child was reported with no antecedent illness. There were no signifi-cant racial difference in the distribution of signs and symptoms of the antecedent illness.

The majority of patients in both racial groups had onset of their antecedent illness between No-vember and April. The distributions of patients, by month of onset of their antecedent illness, were not significantly different.

Outcome of the episode of Reye syndrome is shown by race on the accompanying Table. Though the outcomes by race were not significantly differ-ent


= 3.35, .05 < P < .1), the death-to-case ratio for the black and white children was 54% to 29%, respectively.

The age distributions of the two racial groups are shown in the accompanying Figure. A greater

pro-TABLE. Reye Syndrome in Children Less

Old, Outcome of Illness by Race

than 1 Year


Race Recovered Recovered Died without with

Residual Residual

Black 5 7 14

White 13 7 8

Cl) z Cli 4 0. Figure. and age.

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‘ portion of black than white infants (58% vs 25%)

had onset of Reye syndrome in the first five months of life. The difference in age distribution between the races was statistically significant (Mann-Whit-ney U test, P = .004).

Nineteen of the 26 black children were male. Based on the race-specific sex distributions in the United States for children <1 year old, the binomial probability of the observed excess of males was 0.02. Black males predominate at each month of age. The sex distribution for whites, 12 males and 15 females, did not differ significantly from the ex-pected.


Data presented in this study extend the previous observation’ that race-specific differences exist in the epidemiology of Reye syndrome in children <1 year old. Although overall only 8% of children of all ages reported to the CDC are black, 48% of children <1 year old are black.

The clinical nature of the antecedent illnesses and the months of onset of the antecedent illness did not differ between black and white children <1 year old and are similar to the general pattern seen in Reye syndrome.5 However, there was a prepon-derance of males among the black children, and black infants were more likely than white infants to get Reye syndrome in the first few months of life. Black children comprise a majority of cases re-ported in the first five months of life, while white male patients predominate from 6 months of age on. Both the sex and age differences were statisti-cally significant. There was a trend toward more severe outcome for black as compared to white children; however, the increased proportion of blacks <6 months of age may account for this trend.

These data must be interpreted with caution. They pertain only to children ill enough to be diagnosed and who are not necessarily represents-tive of the full spectrum of Reye syndrome.4 The numbers of patients are small, and they were not collected by a uniform system. Nonetheless, our data are consistent with previous observations that race-specific differences may exist in the

epide-miology of Reye syndrome.24 The observed differ-ences may result from a pathophysiologic subset of the “syndrome” that is related to age, race, and sex, and/or they may point to sociologic and environ-mental components of the etiology of Reye syn-drome. The apparent rarity of Reye syndrome in children <1 year old makes it imperative that the diagnosis be looked for and that each of these children be intensely studied clinically and epide-miologically.


The authors wish to thank the many physicians, nurses, hospitals, and state and local health departments whose investigations and reports have made this study possible.




Center for Disease Control Atlanta

THE OHIO STATE DEPARTMENT OF HEALTH REYE SYNDROME INVESTIGATION GROUP (James S. Marks, MD; Deane Johnson, BS; Frank Holtzhauer, BS; Frank Bright, MS; Taylor Kramer, BS; Thomas J. Halpin, MD)


1. Huttenlocher, PR, Trauner DA: Reye’s syndrome in infancy. Pediatrics 62:84, 1978

2. Nelson D, Sullivan-Bolyai J, Marks, J, et al: Reye’s syn-drome: An epidemiologic assessment based on national sur-veillance 1977-1978 and a population based study, Ohio

1973-1977, in Crocker JFS (ed): Reye’s Syndrome II. New York, Grune & Stratton, 1979, pp 33-50

3. Corey L, Rubin RJ, Thompson TR, et al: Influenza-B asso-ciated Reye’s syndrome: Incidence in Michigan and potential for prevention. J Infect Dis 135:398, 1977

4. Corey L, Rubin LU, Hattwick MAW, et al: A nationwide outbreak of Reye’s syndrome: Its epidemiologic relationship to influenza B. Am J Med 61:615, 1976

5. Van Caillie M, Morin CL, Roy CC, et al: Reye’s syndrome:

Relapses and neurological sequelae. Pediatrics 59:244, 1977

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Thomas J. Halpin

James S. Marks, Deane Johnson, Frank Holtzhauer, Frank Bright, Taylor Kramer and

John Z. Sullivan-Bolyai, David B. Nelson, David M. Morens, Lawrence B. Schonberger,

Reye Syndrome in Children Less than 1 Year Old: Some Epidemiologic Observations


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Thomas J. Halpin

James S. Marks, Deane Johnson, Frank Holtzhauer, Frank Bright, Taylor Kramer and

John Z. Sullivan-Bolyai, David B. Nelson, David M. Morens, Lawrence B. Schonberger,

Reye Syndrome in Children Less than 1 Year Old: Some Epidemiologic Observations

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