Clinical research abstracts for pediatricians☆
Article Outline
- 1. Context
- 2. Objective
- 3. Design
- 4. Study identification
- 5. Study selection
- 6. Results
- 7. Conclusions
- 8. Comment
- 9. Context
- 10. Objective
- 11. Design
- 12. Setting
- 13. Participants
- 14. Main outcome measures
- 15. Results
- 16. Conclusion
- 17. Comment
- 18. Reference
- 19. Context
- 20. Objectives
- 21. Design
- 22. Setting
- 23. Participants
- 24. Main outcome measures
- 25. Results
- 26. Conclusions
- 27. Comment
- 28. Reference
- 29. Context
- 30. Objectives
- 31. Design
- 32. Setting
- 33. Participants
- 34. Interventions
- 35. Main outcome measures
- 36. Results
- 37. Conclusions
- 38. Comment
- 39. Context
- 40. Objectives
- 41. Design
- 42. Setting
- 43. Participants
- 44. Interventions
- 45. Main outcome measure
- 46. Results
- 47. Conclusions
- 48. Comment
- Copyright
Whispered voice test for screening for hearing impairment in adults and children: systematic review
Pirozzo S, Papinczak T, Glasziou P. BMJ 2003;327:967-71
1. Context
Hearing impairment can severely affect young lives by retarding language acquisition and cognitive development. Screening for hearing impairment in children is an integral part of overall health assessment and can be accomplished with a variety of simple tests conducted in the office.
2. Objective
To determine the accuracy of the whispered voice test in detecting hearing impairment in adults and children.
3. Design
Systematic review of studies of test accuracy.
4. Study identification
Studies were identified by searching MEDLINE, Embase, Science Citation Index, unpublished theses, manual searching of bibliographies of known primary and review articles, and contact with authors.
5. Study selection
Two reviewers independently selected and extracted data on study characteristics, quality, and accuracy of results. Studies were included if they had cross-sectional designs, at least one of the index tests was the whispered voice test, and the reference test (audiometry) was performed on at least 80% of the participants.
6. Results
The eight studies that were found used six different techniques. The sensitivity in the four adult studies was 90% or 100%, and the specificity was 70% to 87%. The sensitivity in the four childhood studies ranged from 80% to 96%, and specificity ranged from 90% to 98%.
7. Conclusions
The whispered voice test is a simple and accurate test for detecting hearing impairment. There is some concern regarding the lower sensitivity in children and the overall reproducibility of the test, particularly in primary care settings.
8. Comment
Although audiometry is the gold standard for testing hearing, a clinical screening test would be useful when access to audiometry is limited, such as in primary care or the developing world. This is a well-performed systematic review of the accuracy of free-field voice (“whisper”) testing. The authors identified four studies in adults (290 subjects, mostly elderly; prevalence of hearing impairment 26-61%) and found the test to be sensitive (90-100%) and specific (80-87%) for audiometric thresholds of 30 dB or more. In the four studies in children (716 subjects, aged 3-12; prevalence of hearing impairment 9-31%), however, the test fared less well. The specificity (90-98%) was higher than in adults, but the sensitivity was lower (80-96%). This is a concern for those using free-field voice testing as a screening tool in children, because it implies that many hearing-impaired children will be missed. The authors found some variation in test methods in the different studies, especially in children. They also identified one study suggesting considerable variation in test results between examiners, presumably due to varying loudness of the whispered voice. More studies are needed, preferably in a primary care setting, to identify the ideal test method for children.
Haytham Kubba, MPhil FRCS (ORL-HNS)
Consultant Paediatric Otolaryngologist
Royal Hospital for Sick Children
Glasgow, Scotland G3 8SJ
Timing of initial cereal exposure in infancy and risk of islet autoimmunity
Norris JM, Barriga K, Klingensmith G, et al. JAMA 2003;290:1713-20
9. Context
Although subject to marked inconsistencies within the literature, dietary exposure in infancy has been ascribed as a risk factor in the etiology of type 1 diabetes mellitus (DM).
10. Objective
To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA).
11. Design
Birth cohort study (1994 to 2002, mean follow-up of 4 years (range, 9 months to 9 years).
12. Setting
A general newborn screening at St Joseph Hospital (Denver, Col), with recruitment of first-degree relatives of type 1 DM persons recruited from the local community.
13. Participants
1183 children at increased risk for type 1 DM (high-risk HLA genotype or those having a first-degree relative with type 1 DM). Exposure and outcome measures were obtained for 76% of enrolled children.
14. Main outcome measures
Blood draws for the detection of insulin autoantibody, glutamic acid decarboxylase autoantibody, or IA-2 autoantibody were performed at 9, 15, and 24 months and annually thereafter.
15. Results
Children initially exposed to cereals between ages 0 and 3 months (hazard ratio [HR], 4.32; 95% CI, 2.0-9.35) and those who were exposed at 7 months or older (HR, 5.36; 95% CI, 2.08-13.8) had increased hazard of IA formation compared with those who were exposed during the fourth through sixth month, after adjustment for HLA genotype, family history of type 1 DM, ethnicity, and maternal age.
16. Conclusion
There may be a time window of exposure to cereals in infancy that may increase the risk of developing IA, a marker associated with increased susceptibility to development of type 1 DM.
17. Comment
Over the past few years and with increasing frequency, newspaper captions have informed the public that a variety of infectious agents, dietary constituents, or behavioral practices were “the cause” of type 1 DM. A few widespread examples include childhood immunizations, early consumption of cow's milk, and lack of breast-feeding. Such public dissemination at early stages of research has been harmful to the lay audience (often provoking intense anxiety and guilt, especially in parents of children with type 1 DM). This new study,1 as well as an accompanying study from Germany,2 suggests that the age at which an infant is fed cereal is important in determining his or her risk of type 1 DM. Both studies failed to provide support for the hypothesis that early exposure to cow's milk might be responsible. These two groups have done an outstanding job in terms of their ascertainment, scientific design, and implementation. However, limitations exist including a major one beyond practical control, that of time for and quantity of subject assessment. The degree of certainty as to what story is being told with two or three isolated samples over a significant period of time and in isolation is uncertain. Additional caution should be given for two of the glaring inconsistencies between the two investigations,1,2 one being the increased risk associated with providing cereal before four months of age (a finding in both studies), and that after seven months of age (an observation unique to the Norris et al investigation1), as well as differences in the composition of the diets (ie, rice vs non-rice containing diets). Finally, one must remember that most of these conclusions were based on the development of type 1 DM-associated autoantibodies and not the actual development of type 1 DM. Until such studies are extended to the development of type 1 DM diagnosis, all conclusions should be considered as provisional. In an accompanying editorial to these publications,3 the need for “cautious interest” was noted and I believe this to remain the best stance for the type 1 DM research community and for general pediatricians. Simply put, parents should be encouraged to continue to practice the American Academy of Pediatrics guidelines surrounding the timeline for early infant nutrition.
Mark A. Atkinson, PhD
Sebastian Family Eminent Scholar for Diabetes Research
Department of Pathology
The University of Florida
Gainesville, FL 32610-0275
18. Reference
1. Norris JM, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 2003;290:1713-20.
2. Ziegler AG, et al. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA 2003;290:1721-8.
3. Atkinson M, Gale EA. Infant diets and type 1 diabetes: too early, too late, or just too complicated? JAMA 2003;290:1771-2.
Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress
Waisbren SE, Albers S, Amato S, et al. JAMA 2003;290:2564-72
19. Context
Tandem mass spectrometry now allows newborn screening for more than 20 biochemical genetic disorders. Questions about the effectiveness and risks of expanded newborn screening for biochemical genetic disorders need to be answered before its widespread acceptance as a state-mandated program.
20. Objectives
To compare newborn identification by expanded screening with clinical identification of biochemical genetic disorders and to assess the impact on families of a false-positive screening result compared with a normal result in the expanded newborn screening program.
21. Design
Prospective study involving an inception cohort of newly diagnosed children.
22. Setting
Massachusetts, Maine, and a private laboratory in Pennsylvania with expanded newborn screening; other New England states with limited screening.
23. Participants
Families of 50 affected children identified through expanded newborn screening (82% of eligible cases); 33 affected children identified clinically (97% of eligible cases); 94 screened children with false-positive results (75% of eligible cases); and 81 screened children with normal results (63% of eligible cases).
24. Main outcome measures
Child's health and development and the Parental Stress Index.
25. Results
Within the first 6 months of life, 28% of children identified by newborn screening compared with 55% of clinically identified children required hospitalization (P
=.02). One child identified by newborn screening compared with 8 (42%) identified clinically performed in the range of mental retardation (P < .001). Mothers in the screened group reported lower overall stress on the Parental Stress Index than mothers in the clinically identified group (z=3.38, P < .001). Children with false-positive results compared with children with normal results were twice as likely to be hospitalized (21% [n=20] vs 10% [n=8], respectively; P=.06). Mothers of children in the false-positive group compared with mothers of children with normal screening results attained higher scores on the Parental Stress Index (z=4.25, P < .001) and the Parent-Child Dysfunction subscale (z=5.30, P < .001).
26. Conclusions
Expanded newborn screening may lead to improved health outcomes for affected children and lower stress for their parents. However, false-positive screening results may place families at risk for increased stress and parent-child dysfunction.
27. Comment
Pressure on health departments and hospitals to adopt tandem mass spectrometry has come from malpractice suits and advocacy groups. A private, for-profit screening laboratory, Pediatrix Inc (formerly Neo Gen Screening Inc), also markets tandem mass spectrometry to hospitals and states. At least partly as a result of these pressures, tandem mass spectrometry is now mandated in 22 states, despite continuing lack of evidence of its safety and effectiveness. Although the study by Waisbren et al suggests that some infants will benefit from newborn tandem mass spectrometry screening and appropriate follow-up intervention (especially advising parents that their infants may not tolerate long fasts), doubts remain about the necessity of intervening for some of the disorders (and indeed some diagnosed infants were not treated but may have been labeled as affected), and about the long-term consequences of false-positive test results on parents and, perhaps, on their children. Five infants identified by tandem mass spectrometry (almost 10% of infants detected) were not saved and one infant, despite treatment, performed in the range of mental retardation.
A strength of this study is that it is the first to use standard developmental assessment instruments and a standard measure to examine stress level. In comparing developmental outcomes of the tandem mass spectrometry-screened group to clinically identified infants, the authors did not give the developmental scores either by disorder or by whether the screened infants were treated. Thus, it is not clear that the infants who were screened with tandem mass spectrometry and did better than the comparison group did so as a result of treatment, or because the screened group was weighted more heavily towards benign conditions. Moreover, the only valid comparison between screened and clinically identified infants would be of infants of the same age. When the authors did this, the statistical significance of the differences was less than when they compared older clinically identified infants with younger screened infants. This may be partly due to the reduced sample size.
I strongly concur with Waisbren et al that “questions remain” about the benefits and risks of tandem mass spectrometry screening.1 Whether their data will be used to bolster arguments for or against tandem mass spectrometry screening depends on whether that “glass” is looked at “half full or half empty.” At this stage, states that already have invested in tandem mass spectrometry are unlikely to give it up, whereas most of the other states will probably continue to wait and see. What's most important is that physicians caring for infants and children be aware of the conditions for which newborns are screened in their respective states and hospitals (see http://genes-r-us.uthscsa.edu/resources/newborn/screenstatus.htm).
Neil A. Holtzman, MD, MPH
Genetics and Public Policy Studies
The Johns Hopkins University
Baltimore, MD 21205
28. Reference
1. Holtzman NA. Expanding newborn screening: how good is the evidence? JAMA 2003;290:2606-8.
Inhaled nitric oxide in premature infants with the respiratory distress syndrome
Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. N Engl J Med 2003;349:2099-107
29. Context
Inhaled nitric oxide (iNO) improves gas exchange, decreases pulmonary vascular lability, and reduces pulmonary inflammation.
30. Objectives
To determine whether iNO would decrease the incidence of chronic lung disease (CLD) and death in premature infants with respiratory distress syndrome (RDS).
31. Design
Randomized, double-blind, placebo-controlled study.
32. Setting
University of Chicago Children's Hospital.
33. Participants
207 premature infants (less than 34 weeks' gestation) who were undergoing mechanical ventilation for RDS.
34. Interventions
Infants were randomly assigned to receive iNO (10 ppm on the first day, followed by 5 ppm for six days) or inhaled oxygen placebo for seven days. Infants in each group were further randomized to receive intermittent mandatory or high-frequency oscillatory ventilation.
35. Main outcome measures
The primary outcome measures were death or the development of CLD.
36. Results
In the group given iNO, 51 infants (48.6%) died or had CLD compared with 65 infants (63.7%) in the placebo group (RR, 0.76; 95% CI, 0.60-0.97; P=.03). There was no significant difference between the nitric oxide and placebo groups in the overall incidence of intraventricular hemorrhage and periventricular leukomalacia (33.3% and 38.2%, respectively), but the group given iNO had a lower incidence of severe intraventricular hemorrhage and periventricular leukomalacia (12.4% vs 23.5%; RR, 0.53; 95% CI, 0.28-0.98; P=.04). The type of ventilation had no significant effect on the outcome.
37. Conclusions
The use of iNO in premature infants with RDS decreases the incidence of CLD and death.
38. Comment
Inhaled nitric oxide is now established as an efficacious and safe therapy for term or near-term infants with persistent pulmonary hypertension, and is able to keep some of these infants from needing cardiopulmonary bypass or extracorporeal membrane oxygenation. As acute and chronic neonatal lung disease in preterm infants also frequently has a component of pulmonary hypertension, a possible role for iNO in the therapy of such infants seems a logical next step. The study of Schreiber et al thus represents an important contribution.
With respect to efficacy, Schreiber et al documented a significant benefit, defined by a decline in death or CLD rates, in the iNO-treated premature infants, most notably those with mild or moderate as opposed to severe respiratory distress. This is somewhat surprising and suggests that we need to acquire greater understanding of the mechanisms of action of iNO in these infants. Such potential mechanisms include pulmonary vasodilation and bronchodilation, as well as possible effects on the immune system and surfactant turnover. It is also unclear whether the observed benefits in this population might be applicable to other sites, because the morbidity in the control subjects of the Schreiber study was relatively high.
With respect to safety, the decreased incidence of severe intraventricular hemorrhage and periventricular leukomalacia is encouraging. The potential for intracranial hemorrhage is increased in preterm infants who receive iNO through mechanisms that include decreased platelet aggregation. The risk of ischemic and/or hemorrhagic lesions in the iNO-treated preterm infants may depend on the timing of NO inhalation and the concentration of NO used. Data from currently ongoing studies using different concentrations of NO at different postnatal ages will go a long way to resolving key safety concerns. Meanwhile, use of this therapy in preterm infants should be reserved for clinical trials.
Richard J. Martin, MB, FRACP
Rainbow Babies and Children's Hospital
Case Western University
Cleveland, OH 44106-4920
Randomised controlled trial of treatment of unilateral visual impairment detected at preschool vision screening
Clarke MP, Wright CM, Hrisos S, Anderson JD, Henderson J, Richardson SR. BMJ 2003;327:1251-5
39. Context
Recent studies have raised concerns about the appropriateness of amblyopia as a target condition for early screening and the possible adverse psychologic impact of treatment weighed against the limited disability it causes.
40. Objectives
To test the efficacy of treatment for unilateral visual loss detected by preschool vision screening and the extent to which effectiveness varies with initial severity.
41. Design
Randomized controlled trial.
42. Setting
Eight eye departments in the United Kingdom.
43. Participants
177 children aged 3 to 5 years with mild to moderate unilateral impairment of acuity (20/30 to 20/100) detected by screening.
44. Interventions
Full treatment (with glasses and patching, if required) was compared with glasses only, or with no treatment.
45. Main outcome measure
Masked assessment of best corrected acuity after one year of follow-up.
46. Results
Children in the full and glasses treatment groups had incrementally better visual acuity at follow-up than children who received no treatment, but the mean treatment effect between full and no treatment was equivalent to only one line on a Snellen chart (0.11 log units; 95% CI, 0.050-0.171; P < .0001). The effects of treatment depended on initial acuity: full treatment showed a substantial effect in the moderate acuity group (20/100 to 20/60 at recruitment) and no significant effect in the mild acuity group (20/30 to 20/40 at recruitment) (P=.006 for linear regression interaction term). For 64 children with moderate acuity loss, the treatment effect was 0.20 log units, equivalent to one to two lines on a Snellen chart. When all children had received treatment, six months after the end of the trial, there was no significant difference in acuity between the groups.
47. Conclusions
Treatment is worthwhile in children with the poorest acuity, but in children with mild unilateral acuity loss there was little benefit. Delay in treatment until the age of 5 years did not seem to influence effectiveness.
48. Comment
Preschool vision screening for the detection of amblyopia is widely recommended. Although previous observational studies have supported the benefit of early treatment, there is debate regarding the real value of preschool vision screening because no previous randomized trials of amblyopia treatment have included a no-treatment arm. In this study, children with moderate impairment (20/60 or worse) improved somewhat with glasses and to a greater extent with a combination of glasses and patching compared with those who did not receive any therapy. In contrast, those with mild impairment (20/30 or 20/40) had minimal improvement. The effectiveness of treatment was not decreased among the untreated group after 12 months; furthermore, fewer of these children ultimately required patching. These data support the argument that screening is important for at least a subset of children, but is not helpful in specifying the optimal age for screening. An important limitation is that precise treatment was not described. There is a wide variation in threshold for correction with glasses or initiation of patching. Other treatments, such as blurring vision with eye drops instead of patching, may be more effective than traditional therapy and may have led to greater differences between the treated and untreated groups.
Alex R. Kemper, MD, MPH, MS
Child Health Evaluation and Research (CHEAR) Unit
University of Michigan
Ann Arbor, MI 48109-0456
ALSO NOTED
Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: A randomized controlled trial
Saiman L, Marshall BC, Mayer-Hamblett N, et al. JAMA 2003;290:1749-56
This is a well-designed multicenter, randomized controlled trial of azithromycin (24 weeks of 250 mg or 500 mg based on weight vs placebo) in patients older than 6 years (90% older than age 12) with cystic fibrosis who were chronically infected with Pseudomonas aeruginosa. The primary outcome, improvement in forced expiratory volume at one second, was significantly better in children treated with azithromycin. The drug appeared safe (but the study was not specifically powered to look at these outcomes) and treated patients had fewer cystic fibrosis exacerbations.
Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis
Owen CG, Whincup PH, Gilg JA, Cook DG. BMJ 2003;327:1189-95
Several studies have suggested that breast-feeding may be related to lower blood pressure in adulthood. This well-executed meta-analysis examined 29 articles that explored this hypothesis. The authors conclude that selective publication of small studies indicate some reduction in systolic blood pressure, but that larger studies document only a small reduction in systolic blood pressure (∼1 mm Hg), which is of limited clinical significance.
☆ Editor's Note: Journals reviewed for this issue: New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, The Lancet, Pediatric Infectious Diseases Journal, and Archives of Disease in Childhood. Gurpreet K. Rana, BSc, MLIS, Taubman Medical Library, University of Michigan, contributed to the review and selection of this month's abstracts.
PII: S0022-3476(04)00139-8
doi:10.1016/j.jpeds.2004.02.018
© 2004 Published by Elsevier Inc.
