This Month in the Journal

THE EDITORS’ PERSPECTIVE

THIS MONTH IN THE JOURNAL INACTIVITY

HELPING

IN ADOLESCENTS

It appears that the prevalence and severity of obesity are increasing in adolescents. This is associated with increasing morbidity, such as type II diabetes mellitus. There are ethnic differences in the development of obesity. In this issue Gordon-Larsen et al describe an evaluation of physical activity and inactivity in adolescents, using data from a nationally representative sample collected in 1996. They found that non-Hispanic blacks and Hispanics had the highest levels of inactivity, particularly in hours of television watching. The lowest level of physical activity was observed in nonHispanic blacks and Asian females.This is of particular interest because although Asian females had low activity scores, they also had low inactivity scores and low levels of obesity. These results have important implications for public health policy. If we are to stop the rising tide of obesity, we must know the important areas for intervention. It appears that it will be important to develop strategies directed at both increasing physical activity and decreasing inactivity in children and adolescents. —Stephen R. Daniels, MD Page 301

METHOTREXATE

FOR JUVENILE IDIOPATHIC

ARTHRITIS

The dilemma of how to manage a chronic disease, such as chronic arthritis, is confounded when there are significant concerns regarding the efficacy and/or toxicity of any therapeutic agent. Ideally, targeted therapy could be developed, and specific markers predicting a beneficial response with lack of side effects could be identified. We are not there yet. However, Ravelli et al sought predictors of efficacy and risk factors for toxicity in children receiving methotrexate for chronic arthritis; the study offers useful guidance in decision making regarding the treatment of these diseases. Incidentally, please pay attention to the terminology used by the authors to characterize this form of chronic arthritis. The authors have introduced the term JIA (juvenile idiopathic arthritis) according to the newly proposed revised criteria developed by an international task force.

INNER-CITY FAMILIES MANAGE ASTHMA

The potential benefits of providing a counselor who is an asthma expert to the caregivers of children with asthma have been evaluated by the National Cooperative Inner-City Asthma Study Group.The intervention group had fewer days with symptoms and a trend toward decreased hospitalization rates compared with the control group. It appears that children with severe asthma benefitted most, and in all patients the improvement was maintained during 1 year of follow-up. —Robert W.Wilmott, MD Page 332

MORE

NEW WAYS TO VENTILATE INFANTS IN THE

FUTURE

Infant ventilators are changing more rapidly than they can be evaluated.The demonstration that a new style of ventilation, a new triggering device, or a new monitoring device can improve ventilation or decrease the work of breathing is just the start of evaluations for efficacy. The second step is to demonstrate clinical effects that should correlate with better outcomes. Such effects might include earlier extubation, lower oxygen requirements, less use of glucocorticoids, and a lower incidence of chronic lung disease. Ultimately, a new approach to ventilating infants, whether new equipment or a new strategy, should require proof that long-term neurodevelopmental outcomes are at least equivalent to those achieved with conventional ventilation. Schulze et al report on a technique to mechanically assist the ventilation of preterm infants in proportion to the degree of lung abnormality. The lower pressures required to achieve comparable blood gas values with proportional assist ventilation suggest that there may be long-term benefits, but those studies remain to be done. —Alan H. Jobe, MD, PhD Page 339

—William F. Balistreri, MD Page 316 THE JOURNAL

OF

PEDIATRICS

SEPTEMBER 1999 19A

GLUCOCORTICOIDS:THE

UNANSWERED BALANCE

GROWTH

HORMONE THERAPY: SOMETHING ELSE

BETWEEN RISK AND BENEFIT IN THE PRETERM INFANT

TO CONSIDER

There are now numerous relatively large randomized and controlled trials of glucocorticoids to prevent or treat bronchopulmonary dysplasia. These trials use a wide range of doses and treatment schedules at different times after birth. Because antenatal glucocorticoids decrease the incidence of postnatal intraventricular hemorrhage (IVH), Kopelman et al asked whether a single dose of 0.2 mg/kg dexamethasone within 2 hours of delivery would decrease the incidence of severe IVH. They also asked secondary questions about neonatal adaptation, based on experimental and clinical reports of the effects of antenatal glucocorticoids. The trial was stopped because the incidence of severe IVH decreased in the population of very preterm infants,resulting in the availability of insufficient numbers of infants for testing the primary hypothesis, probably because 87% of the infants were exposed to antenatal glucocorticoids. The single dose of dexamethasone did significantly decrease the need for mechanical ventilation, increase blood pressure, and decrease the numbers of infants treated with indomethacin for patent ductus arteriosus, without significant increases in other complications. Significant is the operative word for a trial that was significantly underpowered to evaluate risks. The nonsignificant associations with dexamethasone treatment were an increase in mortality rate from 15% to 27%, an increase in necrotizing enterocolitis from 9% to 14%,and an increase in severe IVH from 12% to 22%.These poor outcomes are decreased by treatment with antenatal glucocorticoids. The significant positive effects from postnatal glucocorticoids need to be balanced by the statistically insignificant but severe complications that occurred approximately twice as commonly after a single dose of dexamethasone within 2 hours of birth.

A decade ago, the indication for the therapeutic use of human growth hormone (hGH) was quite straightforward: growth hormone (GH) deficiency. Along with the availability of recombinant hGH has come an ever-increasing variety of indications. Today, only very few children receiving the drug have actual GH deficiency. Although the appropriateness of many of these indications has been questioned, concern about the potential side effects of therapy has been very limited. In this light, the report by Bertelloni et al is noteworthy. Four young men without GH deficiency who received hGH therapy were noted to have hypergonadotropic hypogonadism.As the accompanying editorial by Frasier stresses, it is clearly premature to attribute this observation to the therapy. On the other hand, it is quite possible that this complication could be overlooked unless a patient were to seek evaluation for a fertility problem. Abnormality in testicular size and texture may be the only physical finding, and the laboratory test results that were abnormal would rarely be performed as a “routine” in most children receiving hGH today. As Frasier reminds us, the non-endocrinologists, who have become the major prescribers of GH, need to dust off their orchidometers!

—Alan H. Jobe, MD, PhD Page 345

SURPRISES WITH

NEUROIMAGING OF THE

PRETERM INFANT

Very preterm infants frequently have severe brain bleeding and white matter lesions called periventricular leukomalacia. Both these ultrasonographic findings correlate strongly with poor developmental outcomes. However, many preterm infants without these findings develop abnormally. Maalouf et al followed up a cohort of very low birth weight infants with repetitive magnetic resonance imaging until term and describe the normal changes in white matter that occur with development.They also observed a variety of abnormalities in the majority of the infants. The challenge for the future is to determine what may cause the MRI abnormalities and which abnormalities predict which outcomes. The recently described association of antenatal and postnatal exposure to indicators of proinflammation with the subsequent development of cerebral palsy may identify preterm infants who are candidates for study by MRI.

—Thomas R.Welch, MD Page 367

RETICULAR

DYSGENESIS AND DEAFNESS

Sometimes therapeutic interventions save lives, the living of which help us to better understand the congenital defects. In this regard, Small et al offer a trans-Atlantic, collective experience of 8 infants with the rare syndrome of reticular dysgenesis who had lifesaving bone marrow transplantation in early infancy. Seven of the 8 were found to have an additional abnormality, sensorineural deafness. Because 2 infants had deafness proved before potentially ototoxic events, deafness certainly is part of the congenital syndrome. Its presence in neonates with profound leukopenia provides a clue to the diagnosis of reticular dysgenesis, and thus the urgent need for bone marrow transplantation. —Sarah S. Long, MD Page 387

—Alan H. Jobe, MD, PhD Page 351 20A SEPTEMBER 1999

THE JOURNAL

OF

PEDIATRICS