THE JOURNALOF PEDIATRICS FEBRUARY1999
vice in the United States, was in need of proof in the eyes of the Food and D r u g Administration at the time this study was executed. Patients were seen frequently during this short-term evaluation. No attempt was made to have patients stay in the blinded trial if they were deteriorating, and they had 24-hour access to investigator physicians regarding their asthma status, which was monitored with twice-daily peak flow determinations. We believe that this protocol represents an ethical compromise in that a placebo comparison was accomplished without incurring serious consequences in our patients. This occurred because investigators were very cognizant of their special responsibility to oversee and protect the patient receiving placebo. The fact that 56% of these patients with moderate-to-severe asthma completed this trial reminds us that we both undertreat and overtreat our patients unintentionally. Only a placebo arm brings this problem to light. It is much more difficult to justify long-term placebo-controlled trials of inhaled corticosteroid versus placebo in children with asthma. Not only is symptom control at stake, but there is the possibility of irreversible inflammatory changes if early aggressive therapy is withheld. The risks and benefits of such clinical trials are unsettling. The design of these trials requires great attention to safeguards for patients whose physiologic parameters show worsening and methods to taper therapy for those who may no longer need to be exposed to medication. Coupling good science with good patient care is a major challenge.
Gail Shapiro, MD NorthwestAsthma and Allergy Center Seattle, WA 9/35/94429
Preferential pharyngeal colonization of methicillinresistant Staphylococcus aureus in infants To the Editor: Methicillin-resistant Staphylococcus aureus (MRSA) infection in infants and neonates has become a serious concern not only in high-risk neonatal intensive 252
care units but also in general nurseries. An outbreak of exfoliative toxin A (ETA)-producing M R S A infection occurred in our nursery between J u n e and October 1996. We performed epidemiologic and bacteriologic analyses and found that 12 (42.9%) of 28 infants colonized with M R S A on the fifth day of life remained MRSA-positive 10 months after the outbreak. 1 Among these 12 carrier-infants, M R S A colonized only at the pharynx in 9, only in the nose in 1, and at both sites in 1. In another case nasal culture was negative, pharyngeal culture was not done, and fecal culture was positive for MRSA. Overall, M R S A colonized the pharynx in 10 of 12 cases. All isolates were coagulase type III. Gene analysis with the polymerase chain reaction method revealed the presence of mecA and ETA genes, confirming that the M R S A isolated at follow-up was the same as the original one. Relapse of ETA-related symptoms (impetigo, conjunctivitis, or both) was observed in 4 cases during the 10-month follow-up period. Secondary infection of an infant's brother occurred in 1 case. The nasal cavities have usually been regarded as the site of M R S A coloniZation. Hence, it was surprising that most of the M R S A (10 out of 12) in this study colonized the pharynx; despite repetitive and careful cultures, M R S A was not recovered from the nose. Follow-up studies of M R S A carriage in infants have usually been performed only by means of nasal c u l t u r e J -4 H a d we investigated only nasal swabs, the M R S A carrier rate would have been much lower; 2 (7.1%) of 28 cases and 9 (32.1%) of 28 cases would have been overlooked. We do not know whether this preferential colonization of the pharynx is a common characteristic of M R S A or a specific characteristic of this strain. Nevertheless, when carrier rates of M R S A during infancy are studied, we suggest that pharyngeal and nasal specimens should be obtained.
Takahiro Hayakawa, MD, PhD Tadashi Hayashidera, MD, PhD Kozo Yoneda,MD, PhD Shohei Kagawa, PhD Takashi Kusunok~ MD, PhD Department of Pediatrics and Clinical Research Unit Kyoto National Hospital
Department of Dermatology Kyoto University Department of Clinical Pathology Hyogo Collageof Medicine Department of Pediatrics Kyoto University 9/35/93 776
REFERENcEs 1. Hayakawa T, Hayashidera T, Yoneda K, Kagawa S, Kusuuoki T. Unexpectedly prolonged colonization of exfoliative toxin A-producing methicilliu-resistant Staphylococcus aureus (MRSA) in infants. Eur J Pediatr 1998; 157:781. 2. Hasegawa K, Kawase S, Koshizawa S, Kihara M, Matsuo Y, Doi Y, et al. Preventing nosocomial infection with methieillin-resistant Staphylococcus aureus in a neonatal intensive care unit and natural course of MRSA colonized neonates. J Japan Pediatr Soc 1993; 97:2088-93. 3. Ohta T, Karakawa T, Ueda K. Epidemiological study on nasal carriers of methicillin-resistant Staphylococcusaureus. J Japan Pediatr Soc 1994; 98:1990-4. 4. Mitsuda T, Araki K, Fujita S, Yokota S. Epidemiological analysis of strains of methicillin-resistant Staphylococcusaureus (MRSA) infection in the nursery: prognosis of MRSA carrier infants. J Hosp Infect 1995;31:123-34.
Increased TSH levels in neonates with congenital malformations To the Editor: We read with interest the article by Oakley et al 1 reporting that transient T S H elevation on the fourth day of life is associated with a high incidence of congenital malformations prematurity, and "sickness." A combination of increased perinatal stress and iodine exposure in ill babies m a y be factors. Their recommendation to reevaluate the thyroid status of those infants at a later date is appropriate indeed. We would like to share our experience with a neonatal screening program for congenital hypothyroidism in which thyroxine and T S H are measured from cord blood (therefore excluding iodine exposure on thyroid function). 2 In screening 15,000
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VOLUME 134, NUMBER2 neonates, 3 cases of primary hypothyroidism were diagnosed (prevalence 1 in 5061 births). Hypothyroxinemia was diagnosed in another 5 who died in the immediate neonatal period; all had congenital malformations, but only 3 had elevated cord T S H (26, 87, and 468 ~ U / m L ) . Because all died in the immediate neonatal period, they cannot be classified with certainty as having had transient or permanent hypothyroidism. No postmortem examinations were performed. Although our data support Oakley's findings that T S H levels are elevated in some neonates with congenital anomalies, this is not invariably the case. Cord blood hypothyroxinemia (regardless of T S H levels) is also associated with congenital anomalies. T S H and T4 were measured before any iodine exposure because none of the affected infants in our series was delivered by cesarean section. Cord blood thyroxine measurement eliminates the potential effect of iodine on the T S H level measured after day 4.
H. Narch~ MD, FRCPCH, FRCP Naji Kulaylat, MD, FRCPCH, MRCP A1-Hasa Specially ServicesDivision Saudi Aramco - Al-Hasa Health Center Saudo Aramco Medical Services Org. Mubarraz~ 31311 Saudi Arabia 9/35/94623 REFERENCES 1. Oakley GA, Muir T, Ray M, Girdwood RWA, Kennedy R, Donaldson MDC. Increased incidence of congenital malformations in children with transient thyroid-stimulating hormone elevation on neonatal screening. J Pediatr 1998; 132:726-30. 2. Narchi H, Kulaylat NA. Congenital hypothyroidism screening program: a five year experience. Ann Saudi Med 1996;16:47-9.
Effect on growth of inhaled steroid therapy To the Editor: We read with interest the 2 studies that evaluated growth over a 1-year period in asthmatic children treated with inhaled steroids. 1,2 The studies come to different conclusions: Allen et
al 1 found no effect on growth, whereas Crowley et al 2 found growth appeared to be reduced in children taking inhaled steroids. These discordant results may v e r y well be due to the difference in study design, The study by Crowley et al was not blinded or randomized. As a result, it is impossible to know whether the study's findings are due to selection bias or to a true effect of inhaled steroids. In particular, because inhaled steroids are more likely to be prescribed to children with severe asthma, it is unclear whether the observed growth retardation is caused by (the severity of) the asthma itself, its treatment, or a combination of the 2. 3 The study by Allen et al, in contrast, was randomized, placebo-controlled, and double-blind; in this study the observed effect of inhaled steroids on growth (none) is more likely to be true. In the accompanying editorial 4 it is correctly concluded that inhaled steroids may cause growth retardation but that long-term growth retardation is probably rare. It is worth pointing out that the same argument applies to bone metabolism. Whereas the study by Crowley et al suggests that collagen turnover might be disturbed by inhaled steroids, long-term follow-up studies have shown normal bone mineral density in children receiving longterm inhaled steroid maintenance treatment. 5,6 In the discussion on the risk of the development of cataracts in children, no evidence of cataracts was found after 1 to 15 years of using inhaled steroids. In contrast to y o u r editorial's recommendation, these authors conclude that routine screening for cataracts in the pediatric age group is not warranted. With the previously mentioned additions, it appears valid to conclude that inhaled steroid therapy is safe in the vast majority of asthmatic children, and that routine ophthalmic or bone metabolism status follow-up is not indicated.
Paul L. P. Brand, MD, PhD Ruurd-Jan Roorda, MD, PhD Department of Pediatric Pulmonology Isala Clinics Zwolle, 8000 GM, The Netherlands 9/35/94624
REFERENCES 1. Allen DB, Bronsky EA, LaForce GE et al. Growth in asthmatic children treated with fluticasone propionate. J Pediatr 1998;132:472-7. 2. Crowley S, Trivedi P, Risteli L, Risteli J, Hindmarsh PC, Brooke CG. Collagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids. J Pediatr 1998; 132:409-13. 3. McCowan C, Neville RG, Thomas GE, et al. Effect of asthma and its treatment on growth: four year follow up of cohort of children from general practices in Tayside, Scotland. BMJ 1998;316:672. 4. Wagener JS, Wojtczak HA. Inhaled steroids in children: risks versus rewards. J Pediatr 1998:132:381-3. 5. Agertoft L, Pedersen S. Bone mineral density in children with asthma receiving long-term treatment with inhaled budesonide. Am J Respir Crit Care Med 1998; 157:178-83. 6. Baraldi E, Bollini MC, De Marchi A, Zacchello F. Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evalua6on. Eur Respir J 1994;7:710-14. 7. Simons FER, Persaud MP, Gillespie CA, Cheang M, Shuckett EP. Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids. Lancet 1993:342:776-8.
Infant Hib vaccination and herd immunity To the Editor: Van Alphen e t al 1 describe the first 3 years of surveillance for Hib meningitis in the Netherlands after the introduction of the conjugate vaccine PRPT at a schedule of 3, 4, 5, and 11 months of age without vaccination of older age groups. They demonstrate high efficacy among those in receipt of vaccine but no herd immunity and conelude that at the introduction of Hib vaccination, the vaccine should be given to older children as well. The approach taken in the United Kingdom was different, with the use of a schedule of 2, 3, and 4 months of age (no booster) and the incorporation of a "catch-up" program in which all children up to the age of 48 months were