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Re: Results after incorrect analysis: with whom does the responsibility lie?

Dear Editor

Send letter to journal:
Re: Fever must be differentiated from hyperthermia

Dear Editor

I read with interest the paper by Maayan-Metzger et al.[1]

Unfortunately the term "fever" in the article is equated with "hyperthermia". They write:
"fever... is related primarily to dehydration, breast feeding, infection.."
Dehydration is one the common causes of hyperthermia, that is non-interleukin peripherily-mediated elevation of body temperature. Infection, on the other hand, produces fever, that is interleukin-mediated elevation of body temperature. Therefore the article should be entitled "Elevation of body temerature..." to encompass the two causes of raised body temperature: fever and hyperthermia. The differentiation between the two terms is of practical importantance.

Antipyretics, which act upon the central set-point of the hypothalamus, are ineffective in cases of hyperthermia (physical measures are effective)while antipyretics are helpful in fever. Our nursing staff at this hospital are experienced in differentiating the two conditions. During SCBU round, we see sometimes exposed babies without blankets. The nurses tell us: he/she had a raised body temperature, hence exposure.

Reference

(1) A Maayan-Metzger, R Mazkereth, and J Kuint. Fever in healthy asymptomatic newborns during the first days of life. Arch Dis Child Fetal Neonatal Ed 2003; 88:F312-F314.

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Re: Author's Reply

Dear Editor

We welcome the comment by Hassib Narchi on our paper.[1]

We (and our statistical advisor) think we did analyze our data properly, but it is possible that methods description was lacking. Matching a control new born to each of the study babies was only for the purpose of creating a gestational age balanced control group. From that point on, we compared the statistics of the two groups rather than the individual case-control pairs. Therefore we think that using logistic regression was justified in this case.

We do not have a definite answer to the question about the responsibility raised by Dr Narchi, however we agree that careful and critical reading should precede any clinical use of evidence, even when it is published in a very distinguished publication like the ADC.

Reference

(1) Narchi H. Results after incorrect analysis: with whom does the responsibility lie? [electronic response to Maayan-Metzger et al. Fever in healthy asymptomatic newborns during the first days of life] archdischild.com 2003 http://adc.bmjjournals.com/cgi/eletters/fetalneonatal;88/4/F312#221

Send letter to journal:
Re: Fever in healthy asymptomatic newborns

Dear Editor

We read with interest the article "Fever in healthy asymptomatic newborns during the first days of life" by Maayan-Metzger et al.[1]

The article reinforced awareness about the occurrence of fever in term asymptomatic newborns during early neonatal life. It brought out association of risk factors viz. weight loss, exclusive breast feeding, Caesarean delivery & higher birth weight with fever in otherwise asymptomatic newborns & showed that sepsis was the least common cause of fever in such babies.

The authors are requested to comment on following observations for better confidence and implication of their research outcome.

1.In the study, the mean duration of fever mentioned is 2.9 hrs which is too less a time for early detection in a routine busy maternity ward and also as compared to other similar studies.[2]

2. In the study it has been observed that total leukocyte count > 5000/µl has been considered normal, but upper cutoff of normal count is not defined. In newborns, sepsis can present either as neutropenia or neutrophilia and hence there was a scope of missing babies who had sepsis and had higher leucocyte counts >15000/µl.[3]

3. In contemporary practice of neonatology, febrile newborns with no other symptoms or signs with negative rapid diagnostic tests for sepsis are being managed safely as inpatients for further observation without antibiotic therapy.[4] Hence, it would be useful to know the criteria applied to administer antibiotics to neonates in the present study with stated negative laboratory results for infection.

4. Gaudelus J et al. in his study recommended performing spinal tap in all suspected cases of neonatal sepsis presenting as fever alone.[5] With the mean fever duration of only 2.9hrs, how was a decision taken to perform CSF examination only in 109 out of 122 neonates in the study?

5. As viral infections can also present initially with only fever while other clinical manifestations may appear late and will have negative markers for bacterial infection, it would be useful to observe such febrile babies for a longer period of time so as to avoid missing viral sepsis.[6]

In tropical countries like India, during summer months, healthy neonates on exclusive breast feeds commonly develop fever on day 2 or 3 of life which at times is associated with hypernatraemia, renal failure & occasionally mortality. Such babies are managed with effective environmental cooling, better feeding, intravenous fluids, supportive & symptomatic therapies. The important component of management always includes focused attention to enhance maternal lactation.

References

(1) A Maayan-Metzger, R Mazkereth and J Kuint. Fever in healthy asymptomatic newborns during the first days of life.Arch Dis Child Fetal Neonatal Ed.2003; 88:F312.

(2) Dagan R, Sofer S, Phillip M,Shachak E. Ambulatory care of febrile infants younger than 2 months of age classified as being low risk for having serious bacterial infections. J Pediatr. 1988 Mar; 112(3);355-60)

(3) Jaskiewicz Ja, McCarthy CA, Richardson AC, White KC, Fisher DJ, dagan R, Powell KR Febrile infants at low risk for serious bacterial infection-- an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.Pediatrics. 1994 Sep;94(3):390-6.

(4) Chiu CH, Lin TY, Bullard MJ. Identification of febrile neonates unlikely to have bacterial infections.Pediatr Infect Dis J. 1997 jan;26(1):59-63.

(5) Gaudelus J., Fever in infants under the age of three months without sign of focal infection. Criteria of therapeutic decision.Presse Med.1994 Apr 30-may 7; 23(17): 785-7.

(6) Filippine MM, Katz BZ. Neonatal herpes simplex virus infection presenting with fever alone. J Hum Virol. 2001 Jul-Aug;4(4):223-5.)

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Re: Dehydration: the main cause of fever during the first week of life

Dear Editor

We read with interest the findings of Maayan-Metzger et al. relating fever in healthy newborns during the first days of life.[1]

It is difficult to identify febrile neonates at low risk for serious bacterial infection.[2] Although, no consensus exists on the optimal approach to diagnosis and treatment, current guidelines recommend to admit all febrile infants less than 28 days of age to the hospital and give intravenous antibiotics for 48 to 72 hours. But as mentioned in this report dehydration is the primary cause of fever especially during the first days of life. We retrospectively reviewed the medical charts of patients admitted to our neonatal intensive care unit between 1 May 1999 and 30 September 2003 with the complaint of fever.

The inclusion criteria were; gestational age 37 weeks, 1-7 days of postnatal age excluding the first day of life, axillary or rectal temperature 37.8 ^oC on admission, normal physical examination with well appearance and without any sign focal infection, no history of illness or previous antibiotics.

Overall 46 febrile neonates were included in the study. Most (90-95%) of the babies were exclusively breast fed. Laboratory data of the babies’ included complete blood count, c-reactive protein, serum urea and sodium levels, urinalysis, blood, urine and cerebrospinal fluid cultures. The mean (SD) age on admission was 3.4 (1.9) days. The mean (SD) duration of fever was 2.8 (2.4) hours. Twenty seven infants (58.7%) had lost 8% to 24.3% of their birth weights. In 34 of the babies white blood cell counts were between 5000 and 15,000/mm³. Serum sodium levels were obtained in 35 patients. The mean (SD) serum sodium level was 147 (6.7) mmol/l, and in 14 (40%) of them the levels were equal to or higher than 150 mmol/l. There was a positive correlation between weight loss and high serum sodium levels (p=0.002). The mean (SD) serum urea nýtrogen level was 19.3 (11.1) mmol/l. In 22 (47.8) babies serum bilirubin levels were equal to or greater than 220 mmol/l.

Cultures were positive in seven babies. Coagulase negative staphylococci was recovered from five blood cultures and considered to be contaminated both clinically and a negative repeated culture. In one infant blood culture was positive for staphylococcus aureus and enterococcus grew from the culture of the urine in the other. The majority (82.6%) of admissions were between June and early October, which are the warmest months of the year in this area. In this low risk group of infants only two patients had serious bacterial infection. Compatible with the findings by Maayer-Metzger et al, the results of our study supported dehydration being the main cause of fever during the first week of life. Because of the detection of majority of cases during summer and early autumn environmental temperature could have an additive effect in this population.

References

(1) Maayan-Metzger A, Mazkereth R, Kuint J. Fever in healthy asymptomatic newborns during the first days of life. Arch Dis Child Fetal Neonatal Ed 2003;88:F312-F314.

(2) Baker MD, Bell LM. Unpredictability of serious bacterial illness in febrile infants from birth to 1 month of age. Arch Pediatr Adolesc Med 1999;153:508-511.