Neonatal resuscitation without 100% oxygen

Neonatal resuscitation is at last becoming a science. TheInternational Liaison Committee for Resuscitation has beenrefining and improving recommendations for resuscitationpractices based on research about how to best care for asphyx-iated newborns. The current practice is to use 100% oxygenwith the logic being to correct any oxygen deficit as rapidly aspossible. This month in The Journal, Vento et al from Spainreport that resuscitation of asphyxiated infants randomized toreceive 100% oxygen resulted in hyperoxemia, a delayed onsetof spontaneous breathing and increased biochemical markersof oxidant stress in blood, relative to a room air-treated group.In an accompanying editorial, Kattwinkel reviews the contro-versy about oxygen use for neonatal resuscitation. This type ofresearch is essential from each element of delivery room careto provide the information needed for evidence-based recom-mendations. I anticipate that the delivery room of the futurewill provide oxygen through a blender, allowing for low oxy-gen exposures for most resuscitations but 100% oxygen in oc-casional and critical situations.

—Alan H. Jobe, MD, PhDPage 221 (Kattwinkel)Page 240 (Vento et al)

Clinical research with an n = 1

The article by Picker et al in this issue of The Journal ismuch more than a simple case report of a child with a rare dis-order. It is an example of the way in which careful study of anindividual patient can provide pathophysiologic clues that mayhave much broader applicability. Newborns with defects in theurea cycle typically have devastating neurologic complications,usually associated with cerebral edema. This finding is oftenascribed to hyperammonemia. An alternative hypothesis,however, is the presence of elevated intracellular glutamine inthe central nervous system, resulting in brain edema from hy-perosmolarity. Arginase deficiency is a rare urea cycle defectthat typically presents later in life, without the rapidly down-hill neonatal course seen in the other urea cycle defects. Thechild reported by Picker’s group clearly had arginase deficien-cy, but had a rapidly fatal newborn course associated withcerebral edema. Although the child had only a modest eleva-tion in plasma ammonia, magnetic resonance spectroscopyshowed marked elevation in central nervous system glutamine.Thus, the careful study of this case supports an important rolefor brain glutamine, as opposed to hyperammonemia, in theneurologic deterioration associated with this child’s urea cycledisorder.

—Thomas R.Welch, MDPage 349

THE EDITORS’ PERSPECTIVES

The Journal of Pediatrics March 2003 1A

March 2003 • Volume 142 • Number 3

This Month in

THE JOURNAL OFPEDIATRICS

The Journal of Pediatrics (ISSN 0022-3476) is published monthly by Mosby. Corporate and editorial offices: 11830 Westline Industrial Dr, St Louis, MO 63146-3318.Accounting and circulation offices: Mosby, 6277 Sea Harbor Dr, Orlando, FL 32887-4800. Periodicals postage paid at Orlando, FL 32862, and at additional mailing of-fices. 2003 subscription rates: domestic, $160.00 for individuals and $406.00 for institutions. Printed in USA. POSTMASTER: Send address changes to The Journal ofPediatrics, Mosby, Periodicals Department, 6277 Sea Harbor Dr, Orlando, FL 32887-4800.

Copyright 2003 by Mosby, Inc.

2A March 2003 The Journal of Pediatrics

Diarrhea-negative HUSThe past decade has witnessed a number of advances in

our understanding of the hemolytic-uremic syndrome (HUS).The vast majority of children with HUS have a transient dis-order complicating bacterial enteritis. Specific bacterial toxinshave been implicated in this form of the disorder, which hasan excellent prognosis with appropriate supportive therapy.Recurrence of this form of HUS is almost never seen. A muchsmaller number of children with HUS have no evidence ofpredisposing enteritis. These children are likely to have amuch worse outcome, and are at great risk for recurrences ofthe disease. This “diarrhea-negative” HUS is probably a het-erogeneous group of disorders with a variety of underlyingcauses. One of these causes is nicely demonstrated in the cur-rent issue by Veyradier et al. Of 23 children with diarrhea-negative HUS, six had persistent deficiencies in vonWillebrand factor-cleaving protease (VWF-cp) activity.These children were characterized by a severe neonatal onsetof disease, as well as multiple relapses. In the coming years,expect to find additional such factors underlying HUS, per-haps with distinguishing phenotypes as well. For readers in-terested in more details about diarrhea-negative HUS, wesuggest a recent review by Moake (N Engl J Med2002;347:589-600).

—Thomas R.Welch, MDPage 310

Sharing cellsThe very provocative observation that newborns can

have maternal cells in multiple organs was published in TheJournal in January (Srivatsa et al, J Pediatr 2003;142:31-5).The excellent commentary by Hall in this issue of The Journalhighlights the fascinating new research that tracks the lineageof cells from fetuses to their mothers and the persistence ofthose cells for many years. The article by Srivatsa et al opensthe reciprocal possibility that maternal cells may permanentlycolonize fetuses and newborns.

—Alan H. Jobe, MD, PhDPage 233

Zinc protoporphyrin/heme as an indicator ofiron status in NICU patients

Very-low-birth-weight preterm infants are born with lowiron stores and phlebotomy further depletes total body iron. Theinfants also have complicated antenatal histories and postnataldiseases that can further stress iron status.These infants often donot begin to make reticulocytes for several months despite lowhermatocrits. Independent of hematopoiesis, iron is importantfor other cell functions and its deficiency is associated with neu-rodevelopmental abnormalities. There has been no reliablemethod to evaluate iron status in the preterm. Although ironsupplementation is routine once an infant is stable and feeding,iron supplementation is not tailored to the needs of the infant.Juul et al evaluated the zinc protoporphyrin-to-heme ratio as anerythropoietic-independent laboratory assessment of iron status.The results are promising and suggest that there are categoriesof infants who require additional iron supplementation.

—Alan H. Jobe, MD, PhDPage 273

The Journal of Pediatrics March 2003 3A

Vitamin A studies meet critical analysisThe meta-analysis by Grotto et al on the effect of vita-

min A supplementation in children without frank deficiencyis an “eye-opener.” Painstakingly, the authors judged the pre-viously exposed studies on this topic, focusing on those ad-dressing preventive effects of vitamin A on morbidity (ratherthan mortality) of diarrhea and respiratory tract illness, ex-cluding those in which subjects were likely to be vitamin A-deficient. Their findings are compelling. In a sentence:Children with vitamin A sufficiency are not likely to benefit,and may experience harm from “extra” vitamin A.

—Sarah S. Long, MDPage 297

Therapy of rickets—“Long in the tooth”Hypophosphatemic vitamin D resistant rickets

(VDRR) is a well characterized, X-linked disorder that ismainly characterized by growth failure and rachitic deformi-ties. Carefully monitored therapy with very active vitamin Danalogues and phosphate supplementation can safely correctboth of these problems.

A lesser known complication of VDRR is its impact ondentition. In the days before current therapy was widely avail-able, patients with VDRR typically had severe problems withcaries and tooth loss. In the current issue of The Journal,Chaussain-Miller et al from Paris provide convincing evidencethat modern treatment of VDRR also impacts dental disease.Of the 16 patients in their series who were treated before“modern” vitamin D/phosphate therapy, most had significantdental disease. In contrast, all 32 of the patients treated withthe contemporary approach had normal dentition. Clearly, ap-propriate therapy of VDRR has benefits beyond that of stat-ural growth and the prevention of rickets.

—Thomas R.Welch, MDPage 324

Children with mild-moderate asthma havenormal growth and bone mineral density

The question of whether children with mild-moderateasthma have reduced growth or bone mineralization was stud-ied by Kelly et al in the Childhood Asthma Management Pro-gram (CAMP). In children entering the study, with a 4- to7-year history of asthma, height and bone mineral densitywere normal for age and unaffected by past use of corticos-teroids.

—Robert W.Wilmott, MDPage 286