1992;90;129PediatricsMARIA CASTEELS-VAN DAELE

Ibuprofen Safety  

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LETTERS TO THE EDITOR 129

J�u�s R. Hcx�n, MDPIPPA M. S�wsoN, MDGERARD P. RABALAIS, MDD� L. STEWART, MDLuu�v N. CooK, MD

UIC College of Medicine at PeoriaChildren’s Hospital of Illinois

at St. Francis Medical CenterSection of NeonatobogyPeoria, Illinois 61637

I read with great interest the Letters to the Editor on ibuprofen

and fever. In Europe the pharmaceutical companies also are active

in promoting ibuprofen for the treatment of fever in children; and

here too the debate goes on.

Most physicians agree that young febrile children should be

given antipyretics.3 We are left with a major problem. We banned

aspirin because we were told it induces Reye’s syndrome, and so

we prescribe paracetamol despite its well-known hepatotoxicity.

Now we are faced not only with its fatal acute poisoning, albeit

rare in children, but also with its chronic toxicity, which seems to

be more of a danger.4 Moreover, renal tubular necrosis and hypo-

glycemic coma may occur as well, and a few isolated cases of

hematologic abnormalities have been reported.5

Is ibuprofen the better choice?6 What about this drug’s side-

effects, including gastrointestinal disturbances, agranulocytosis,

thrombocytopenia, toxic amblyopia, blurred vision, aseptic men-

ingitis, and many others?27

Has not the time come to admit that we have made the wrong

deductions, that there is no scientific proof for a link between

aspirin and Reye’s syndrome? In addition to the criticisms already

formulated by others,8” we recently gave further evidence for

major biases in the four main case-control studies suggesting this

link.’2 Indeed, in three of these four Reye’s syndrome surveys, only

the medication usage before the onset of severe vomiting was

registered, thus excluding the drugs, eg, antiemetics, given between

the onset of vomiting and hospitalization.’3’5 Moreover, the Ohio

survey first started by registering all medications taken throughout

the illness, but when these data indicated that not only the use of

aspirin, but also that of phenothiazines and trimethobenzamide

hydrochloride was significantly greater in Reye’s syndrome cases

than in controls, the questionnnaire was revised. Only the medi-

cations given before onset of severe vomiting were then registered

and thus the same bias was introduced as in the other three

surveys.’6 Defining the day of onset of severe vomiting as the onset

of Reye’s syndrome is arbitrary and thus results in incorrect data

as to medication use.

Neither is the apparent disappearance of Reye’s syndrome an

argument for the causal relationship with aspirin. We have all been

overdiagnosing Reye’s syndrome at a time of limited facilities for

virologic, metabolic, and toxicologic analyses. As shown in several

series of Reye’s syndrome meeting the Centers for Disease Control

criteria, the percentage of definite diagnosis vs presumptive diag-

nosis varies between 0% and 35%,17.19 Gauthier et al studied 49

patients retrospectively, diagnosed as Reye’s syndrome between

1970 and 1987. When their charts were reviewed blindly by three

clinicians, the diagnosis of Reye’s syndrome was considered certain

in only one case.2#{176}In conclusion, time has come to re-analyze the epidemiologic

surveys linking Reye’s syndrome to aspirin. lime has come to

reconsider aspirin for the treatment of fever in children. Or shall

we go on, leaning on biased data, and thus expose our young

patients to other risks, known and unknown?

The author has no ongoing affiliation or financial involvement with any

pharmaceutical company nor with any other entity with a financial interest

in the subject matter.

Ibuprofen Safety

To the Editor.-

MARIA CASTEELS-VAN DAELE, MDDepartment of PediatricsUniversity Hospital

Gasthuisberg

University of Leuven3000 Leuven, Belgium

REFERENCES

1. Lorin MI. Ibuprofen for fever. Pediatrics. 1991;87:125-126. Letters to

the Editor.

2. Rosefsky JB. Ibuprofen safety. Pediatrics. 1992;89:166-167. Letters to

the Editor.

3. Management of childhood fever. Lancet. 1991;338:1049-1050. Editorial.

4. Penna A, Buchanan N. Paracetamol poisoning in children and hepato-

toxicity. BrJ Clin Pharmacol. 1991;32:143-149

5. Goodman and Gilman. Pharmacologic Basis of Therapeutics. 8th ed.

1990:658

6. Casteels-Van Daele M. Management of childhood fever. Lancet.

199 1;338: 1408

7. Martindale W. The Extra Pharmacopoeia. 29th ed. London Pharmaceutical

Press; 1989:20-21

8. Clark JH, Fitzgerald JF. Doubts relationship of salicylate and Reye’s

syndrome. Pediatrics. 1981;68:466-467. Letters to the Editor.

9. Gall DG, Barker G, Cutz E. Doubts relationship of salicylate and Reye’s

syndrome. Pediatrics. 1981;68:467-468. Letters of the Editor.

10. Daniels SR. Greenberg RS, lbrahim MA. Scientific uncertainties in the

studies of Reye’s syndrome. JAW. 1983;249:1311-1316

1 1 . Orlowski JP, Gillis J, Kilham HA. A catch in the Reye. Pediatrics.

1987;80:638-642

12. Casteels-Van Daele M. Reye syndrome or side-effects of anti-emetics?

Eur J Pediatr. 1991;150:456-459

13. Starko KM. Ray CG, Dominquez LB. Stromberg WL, Woodall DF. Reye’s

syndrome and salicylate use. Pediatrics. 1980;66:859-864

14. Waldmann RJ, Hall WN, Mc Gee H, Van Amburg G. Aspirin as a risk

factor in Reye’s syndrome. JAW. 1982;247:3089-3094

15. Hurwitz ES, Barrett MJ, Bregman D, et al. Public health service study of

Reye’s syndrome and medications. Report of the main study. JAMA.

1987;257:1905-191 1

16. Halpin TH, Holtzhauer FJ, Campbell RJ, et al. Reye’s syndrome and

medication use. JAW. 1982;248:687-691

17. Rowe PC, Valle D, Brusilow. Inborn errors of metabolism in children

referred with Reye’s syndrome. A changing pattern. JAMA.

1988;260:3167-3170

18. Yoshida I, Yamashita F. The changing age distribution of Reye’s syn-

drome in the United States and a critique of the CDC criteria. Acta

Paediatr Jpn. 1990;32:378-380

19. Forsyth BW, Shapiro ED, Horwitz RI, Viscoli CM, Acampora D. Misdi-

agnosis of Reye’s-like illness. AJDC. 1991;145:964-966.

20. Gauthier M, Guay J, Lacroix 1, Lortie A. Reye’s syndrome. A reappraisal

of diagnosis in 49 presumptive cases. AJDC. 1989;143:1181-1185.

Neonatal Screening for Dependents of Active-DutyMilitary Personnel

To the Editor.-

In the February issue of Pediatrics the Committee on Genetics

issued their most recent statement and recommendations on new-

born screening for metabolic/inherited disorders.’ Within the text

of this statement there is incorrect information concerning newborn

screening for dependents of active-duty military personnel. In the

commentary on universal screening (Goal 2’�346) the Committee

reports:

The absence of a standardized neonatal screening policy or

program for dependents of the United States Uniformed

Services also placed them at increased risk for failure to be

screened, particularly those born outside the US.

The policy for newborn screening in US Army Medical Depart-

ment (AMEDD) hospitals is to observe the standards/guidelines

established by the state, district or territory in which they reside.

This policy is not new.

In 1989, a survey of all AMEDD hospitals providing maternity

and newborn services was conducted to assess neonatal screening

practices. Questionnaires were sent to each of 40 hospitals provid-

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1992;90;129PediatricsMARIA CASTEELS-VAN DAELE

Ibuprofen Safety  

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Online ISSN: 1098-4275.Copyright © 1992 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it

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