Alison Schonwald

The Effect of Chronic or Intermittent Hypoxia on Cognition in Childhood: A Review of the Evidence

Objective. A review of the evidence concerning the effect of chronic or intermittent hypoxia on cognition in childhood was performed by using both a systematic review of the literature and critical appraisal criteria of causality. Because of the significant impact of behavioral disorders such as attention-deficit/hyperactivity disorder on certain cognitive functions as well as academic achievement, the review also included articles that addressed behavioral outcomes. Methods. Both direct and indirect evidence were collected. A structured Medline search was conducted from the years 1966-2000 by using the OVID interface. Both English- and non–English-language citations were included. Significant articles identified by the reviewers up to 2003 were also included. To be included as direct evidence, an article needed to be an original report in a peer-reviewed journal with data on cognitive, behavioral, or academic outcomes in children up to 14 years old, with clinical conditions likely to be associated with exposure to chronic or intermittent hypoxia. Indirect evidence from other reviews and publications in closely related fields, including experimental studies in adults, was used to help formulate conclusions. Two reviewers screened abstracts and titles. Each article included as direct evidence received a structured evaluation by 2 reviewers. Adjudication of differences was performed by a group of 2 reviewers and a research consultant. After this review, tables of evidence were constructed that were used as the basis for group discussion and consensus development. Indirect evidence assigned by topic to specific reviewers was also presented as part of this process. A formal procedure was used to rank the studies by design strength. The critical appraisal criteria for causation described in Evidence Based Pediatrics and Child Health (Moyer V, Elliott E, Davis R, et al, eds. London, United Kingdom: BMJ Books; 2000:46–55) were used to develop consensus on causality. Results. A total of 788 literature citations were screened. For the final analysis, 55 articles met the criteria for inclusion in the direct evidence. Of these, 43 (78.2%) reported an adverse effect. Of the 37 controlled studies, 31 (83.8%) reported an adverse effect. Adverse effects were noted at every level of arterial oxygen saturation and for exposure at every age level except for premature newborns. The studies were classified into 5 clinical categories: congenital heart disease (CHD), sleep-disordered breathing (SDB), asthma, chronic ventilatory impairment, and respiratory instability in infants. Two of these categories, CHD and SDB, which accounted for 42 (76.4%) of the included articles, fulfilled the Evidence Based Pediatrics and Child Health criteria for causation. The indirect evidence included 8 reviews, 1 meta-analysis, and 10 original reports covering the fields of adult anoxia, animal research, SDB in adults, natural and experimental high-altitude studies, perinatal hypoxic-ischemic encephalopathy, anemia, and carbon-monoxide poisoning. The studies of high-altitude and carbon-monoxide poisoning provided evidence for causality. Conclusions. Adverse impacts of chronic or intermittent hypoxia on development, behavior, and academic achievement have been reported in many well-designed and controlled studies in children with CHD and SDB as well as in a variety of experimental studies in adults. This should be taken into account in any situation that may expose children to hypoxia. Because adverse effects have been noted at even mild levels of oxygen desaturation, future research should include precisely defined data on exposure to all levels of desaturation.

Clinical genetic testing for patients with autism spectrum disorders

BACKGROUND: Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. PATIENTS AND METHODS: A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. RESULTS: Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%–2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%–0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%–21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%–8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changes in 7.3% (51 of 697) and 5.3% (8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CONCLUSIONS: CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part of the initial diagnostic evaluation of patients with ASD.

Copy number variation plays an important role in clinical epilepsy

To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center.

Attention deficit/hyperactivity disorder: complexities and controversies.

Purpose of review Attention deficit/hyperactivity disorder continues to be a prevalent childhood behavioral disorder, with significant clinical and media interest. Providers must be current with research findings that impact the evolving understanding of this complex entity. This article summarizes recent progress in our view of attention deficit/hyperactivity disorder, with emphasis on controversies around diagnosis and treatment, and future management directions. Recent findings Literature about attention deficit/hyperactivity disorder in 2005 further enhanced our understanding of the genetic contribution to the expression of attention deficit/hyperactivity disorder, with exploration of sophisticated genetic models and their dynamic interaction with exposures and experiences. Previous literature focuses on conventional treatment; new developments in pharmacological/alternative options add to treatment choices, but have brought well publicized controversies. Furthermore, optimal management continues to gain evidence-based support. Summary Attention deficit/hyperactivity disorder is a subject of great interest to families, providers, researchers, and public forums. Scientific investigation supports a primary genetic contribution, but the relationship of molecular bases and environmental exposures appears intricate and complex. With increased awareness of this disorder, diagnostic dilemmas and medication side effects are more widely understood, topics particularly important to clinicians. Stimulant treatment remains the mainstay of intervention, but new delivery forms and nonstimulant options are potential therapies as well.

Developmental Screening: Is There Enough Time?

Objectives . The American Academy of Pediatrics recommends routine developmental screening in well-child care. Providers cite time restraints as a limitation preventing its widespread adoption. The objectives were to determine whether routine screening lengthened well-visits and was associated with changes in parent satisfaction and report of anticipatory guidance. Methods. Visits before and after implementation of routine screening were timed. Parents whose children were seen before or after screening began were contacted to query their perceptions of the visit. Results. There was no change in visit lengths after the screener was included. With screening, more parents reported their provider talked about their concerns, and that their questions were answered. There were no changes in parent satisfaction ratings or reports of anticipatory guidance discussions. Conclusions. The perceived obstacle that routine screening requires more time than pediatricians have should not prevent its adoption. Screening tools may empower some parents otherwise reluctant to raise concerns unsolicited.

Update: attention deficit/hyperactivity disorder in the primary care office.

Purpose of review Attention-deficit/hyperactivity disorder (AD/HD) affects 7.5% of children, making it among the more common behavioral disorders of childhood. Pediatricians increasingly are expected to recognize AD/HD, as well as diagnose and manage it in the primary care setting. This article reviews recent developments in the care of the pediatric AD/HD patient, with emphasis on information enhancing primary care management. Recent findings Studies published in 2004 provide evidence to guide the treatment of AD/HD. The AD/HD literature continues to support the important role of genetics in its etiology. The absence of universal genetic or neuroimaging findings indicates that history from multiple sources and physical exam remain the standard diagnostic method. Comorbid medical problems, such as sleep disruption and growth suppression, continue to be better understood in the setting of AD/HD, as do the substantial impacts of comorbid learning and psychiatric disorders. Despite great interest in alternative, nonstimulant and behavioral treatments, methylphenidate and amphetamine-based medications remain the mainstay of AD/HD intervention. Summary AD/HD is a common medical condition with implications for long-term safety and life function, such as academic success, accident occurrence, and drug use. Identification and treatment is increasingly based in the primary care office, where children must be monitored for co-occurring disorders and referred for additional supports when necessary. Tools and guidelines provided by the American Academy of Pediatrics (AAP) provide a framework for consistent and competent AD/HD care supported by current evidence.

Developmental Screening With Spanish-Speaking Families in a Primary Care Setting

Cultural beliefs may influence parents’ willingness to raise concerns on a developmental screener. Our study evaluated the performance of the Parents’ Evaluation of Developmental Status (PEDS) in an urban community health center where 75% of families are Spanish speaking. Our primary outcome was the presence of parent-reported concerns either in the medical record or on the PEDS before the PEDS was introduced compared with after it became routine care (post-PEDS). Covariates included family language and child age, gender, and risk status. The adjusted odds of a concern being identified was 1.5 times greater in the post-PEDS period for Developmental concerns and 2.1 times greater for Behavioral concerns. There was no association with family language indicating that the PEDS performs equally well for English- and Spanish-speaking families. The systematic inclusion of developmental screening as part of culturally competent primary care may aid in reducing current disparities in the identification of developmental concerns.

Health Care Transition Planning among Adolescents with Autism Spectrum Disorder.

Improving the health care transition process for youth with autism spectrum disorder (ASD) is critically important. This study was designed to examine the overall national transition core outcome among youth with ASD and each of the component measures of health care transition planning. Fewer than 10% of youth with ASD meet the national transition core outcome. Among youth with ASD, there is greater disparity in health care transition planning for non-Hispanic black youth, youth with family income <400% of the federal poverty line, and youth with more severe activity limitation. Continued advocacy, research, and training efforts are needed to reduce disparities in receipt of health care transition planning services for youth with ASD.