December 2013 Journal Watch

Behavioral & Developmental Pediatrics

Bonnie E. Stephens, MD, Carla M. Bann, PhD, Victoria E. Watson, MS, CAS, Stephen J. Sheinkopf, PhD, Myriam Peralta-Carcelen, MD, MPH, Anna Bodnar, MD, Kimberly Yolton, PhD, Ricki F. Goldstein, MD, Anna M. Dusick, MD, Deanne E. Wilson-Costello, MD, Michael J. Acarregui, MD, Athina Pappas, MD, Ira Adams-Chapman, MD, Elisabeth C. McGowan, MD, Roy J. Heyne, MD, Susan R. Hintz, MD, MS, Epi, Richard A. Ehrenkranz, MD, Janell Fuller, MD, Abhik Das, PhD, Rosemary D. Higgins, MD, Betty R. Vohr, MD. Screening for Autism Spectrum Disorders in Extremely Preterm Infants. J Dev Behav Pediatr 33:535–541, 2012.
Premature infants have an increased risk of developing autism spectrum disorders (ASD). One prior study showed that about twice as many extremely preterm (EP) infants screened positive for ASD as those who had the diagnosis at age 11. It was hypothesized that this may be due to screening EP infants with the same tools as used for the general population rather than using screening tool for infants with neurodevelopmental impairment. 554 infants born at <27 weeks gestation where enrolled over a 1 year time period at 15 hospitals in the US. In addition to history and physical exam, infants were screened at 18 months corrected age using the Bayley Scales of Infant and Toddler Development and the Brief Infant-Toddler Social and Emotional Assessment as well as with 3 ASD screens: Pervasive Developmental Disorders Screening test, Response to Joint Attention, and Response to Name. Among the participants, 20% had a positive ASD screen with only 4% having more than one screen positive. Those with positive screens were more likely to be non-Hispanic white males with lower birth weight, more neonatal complications, more days in the hospital, and have less educated mothers, abnormal behavioral scores, and cognitive/language delays. This study emphasizes the importance of factoring in neurodevelopmental impairment when evaluating EP infants for ASD and using more than 1 screening tool. It will be important as general pediatricians to factor in that ASD screening tools for the general population may not be as effective in EP infants.
Submitted by: Elise Bream
Comment: Neither the challenge of differentiating ASD from developmental delay (DD), nor of screening for autism in toddlers with known DD, is completely unique to the population of extremely premature infants. Work by Mitchell et al (Dev Disabil Rev Res, 2011) endorses response to name in the first year and reduced or atypical use of gestures (including pointing) in the first two years as suggestive of ASD not DD. There is clearly room for screening tools that can help clinicians identify ASD whether or not the child has risk for DD. Lydia Furman MD

Cardiology

Garg, Lorraine F. et al. Results From the New Jersey Statewide Critical Congenital Heart Defects Screening Program. Pediatrics. 2013; 132: 314-323.
In order to improve early detection of critical congenital heart defects (CCHD), New Jersey was the first state to implement legislatively mandated newborn pulse ox screening. This report evaluates this mandate during its first 9 months in effect. Of the 75,324 live births in the state of New Jersey from 8/31/11 through 5/31/12, 73,320 were eligible for screening. 99.1% of eligible newborns were screened. The percentage of missed screens decreased from 1.8% in the first period to 0.2% in the third period. As a direct result of the screening, 30 infants had further evaluation. 3 of the infants were subsequently diagnosed with CCHD. 17 of the infants were subsequently diagnosed with other congenital heart diseases (ex VSD), pulmonary HTN, sepsis, or pneumonia. Up to 20% of CCHDs are not diagnosed prenatally or identified prior to hospital discharges. Early detection of CCHD is important to help reduce morbidity and mortality. The pulse ox screening is a simple tool that aids in the early diagnosis of CCHD, making it possible for these children to seek treatment early.
Submitted by: Shannon Moore
Comment: It seems that this is an effective adjunct to current screening done in the newborn period. The authors point out that the cost of doing pulse oximetry is less than that of metabolic screening tests ($14 vs. $20) and could have results that are just as important. Laura Caserta MD

Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children. Almond et al., Circulation, April 2013.
Children with end-stage heart failure listed for heart transplantation face the highest wait-list mortality in transplantation medicine. The most important reason seems to be the lack of available and reliable miniaturized ventricular assist devices (VADs) for infants and children. The authors of this article report outcomes for US children with end-stage heart failure who received the EXCOR Pediatric VAD as a bridge to heart transplantation. They included all children with paracorporeal EXCOR VADs implanted between May 2007 and December 2010 in the US and Canada. Data from 204 patients is presented: most children (> 75%) received the implantation under compassionate use and not under the original investigational device exemption (IDE) because they met 1 or more exclusion criteria. An IDE permits the use of a device in a clinical study to collect safety and effectiveness data in the process of FDA approval. Exclusion criteria for the study were complex heart disease, significant end-organ dysfunction at implantation, and surgical implantation at any of 27 centers not officially participating in the FDA trial. Published results from the FDA trial include only 1 of 4 children with the device. The combined analysis of all patients reflects the so-called real world experience of the device in an unselected patient cohort. The data shows that overall survival at 1 year on EXCOR support was 75%, with 5% alive with the device in place, 6% recovered with the device explanted and 64% survived to transplantation. The subgroup analysis showed that children in the compassionate use group were less likely to reach transplantation and more likely to die. The strongest predictor for mortality was a reduced glomerular filtration rate for age. The leading cause of death was a neurological insult, most common a thromboembolic stroke, which accounted for 33% of all deaths. Twenty-five percent of patients died and these children were smaller in size, had decreased renal function, increased total bilirubin and biventricular support. As this is the largest patient cohort studied so far it is the first time it could be shown that end-organ dysfunction measured by GFR per age and bilirubin level at time of implantation has a critical impact on survival. Also low patient weight is a risk factor for patient mortality although the exact reason for this finding has not yet been identified. It could be due to the smaller pump size or anatomical structures, age related differences in hemostasis or technical difficulties in supporting slower flow rates through miniaturized components for prolonged time periods. The neurological dysfunction with thromboembolic stroke as the main cause of death suggests a need for further refining the complex management of anticoagulation in this patient population. The study findings led to FDA approval of EXCOR not only in children who meet the FDA trial inclusion criteria (with the best results in this group),but also in "all pediatric candidates with severe isolated ventricular or biventricular dysfunction who are candidates for cardiac transplant and require circulatory support". This study emphasizes the importance of careful patient selection especially in the smallest patients to identify candidates before end-organ damage or decreased right ventricular function occurs. On the other hand, implantation should not be performed too early due to VAD-associated risk of stroke, bleeding or infection.
Submitted by: Lisa Zipp, MD
Comments: This is a terrific summary of a complex situation. Certainly few of us will be directly involved with managing pediatric VADs, but we might have a patient who must have cardiac transplantation and it is helpful to understand some of the technical issues. Lydia Furman MD

Child Advocacy

Rabiner J, Friedman L, Khine H, Avner J, Tsung J. Accuracy of Point-Of-Care Ultrasound for Diagnosis of Skull Fractures in Children. Pediatrics 2013; 131;e1757.
This prospective study assessed the utility of training ED clinicians in point-of-care ultrasound to compare efficacy of diagnosing skull fractures in children. Children were enrolled if they were less than 21 years of age who presented to the ED with head injury suspicious for skull fracture. Physicians were trained for one hour with point-of-care ultrasound to look for and diagnose skull fractures. 17 clinicians using ultrasound examination of the head injury evaluated a total of 69 patients. The results showed specificity of 97% (95% CI: 89-99%) and sensitivity of 88% (95% CI: 53-98%). The only false-negative result with ultrasound scan was for a patient with skull fracture adjacent to a hematoma, not under the hematoma. The study concluded that clinicians with ultrasound training could accurately diagnose skull fracture with a high specificity and avoid CT scan of children. I think there would be a great deal of benefit in performing point-of-care ultrasound exams in patients presenting to the ED with head injury to diagnose skull fracture. The one-hour training session was given to PEM attending physicians and fellows who already were novices in musculoskeletal ultrasound exams. I believe this training could be very beneficial to our PEM department in helping to avoid radiation in children with head injuries.
Submitted by: Lauren Riney
Comments: This does seem promising. It would be important to ensure that the training is standardized to optimize accuracy. Laura Caserta MD

Van Bergen DD, Bos HMW, Van Lisdonk J, Keuzenkamp S, Sandfort TGM. Victimization and suicidality among Dutch lesbian, gay, and bisexual youths. AJPH 2013; 103(1):70-72.
Levine DA, Committee on Adolescence. Technical report: office-based care for lesbian, gay, bisexual, transgender, and questioning youth. Pediatrics 2013;132:e297-e313.

Both suicidal ideation and attempts have been reported as higher in lesbian, gay and bisexual (LGB) youth than heterosexual cohorts. This study, conducted in the Netherlands between May and August 2009, set out to enhance an understanding of the impact of victimization and suicide in LGB youth. Two hundred and seventy-four LGB youth, all in secondary education, were recruited as part of a larger study conducted by the Netherlands Institute for Social Research. Suicide-related parameters were considered over participants’ lifetimes, whereas victimization related to homophobia was recorded from the prior year. Parental, extra-nuclear family, neighborhood and school settings of victimization were evaluated. Prior research in Dutch youth, aged 18-24 years old, has shown 10.3% and 2.2% experience suicidal ideation and suicide attempts, respectively. The contrasting respective 63.9% and 12.8% rates in this LGB study population are concerning. Young males reported more victimization in school and neighborhood settings than young females, although rates reported by parents and other family members were comparable in both sexes. Overall, significant association was found between suicidal ideation and victimization in both school and neighborhood. Victimization at school and by parents was significantly associated with suicide attempt. Although no suicide causality can be ascertained from this study, supportive responses and interactions with LGB youth by peers and parents may reduce both suicidal ideation and attempts in this vulnerable group. The recent technical report from the American Academy of Pediatrics also emphasizes the role pediatricians can play in understanding and offering support to this population. In my family, I saw firsthand the impact of victimization in gay youth. This has heightened my sensitivity to the problems LGB youth face, but the augmented suicide-related risk detailed in this study as well as the current technical report will serve as reminders of how important my role as a pediatrician will be in offering a welcoming environment, support and education for these patients.
Submitted by: Diane Hindman
Comments: Dr. Hindman’s points are well-made and heartfelt. Suicide is the 3rd leading cause of death in adolescents, and it is clear from studies in the US also that rates of suicide are much higher for LGBT teens, with both general and LGBT-specific risk factors contributing (Liu et al Am J Prev Med 2012). Referral for mental health care is also more challenging due to fewer providers with expertise and training in this domain (Rutherford et al Med Educ 2012). We clearly have a long way to go, but can each challenge ourselves to improve our own approach to youth identifying as LGBT. Lydia Furman MD

Emergency Medicine

Mittal MK, et al. Performance of ultrasound in the diagnosis of appendicitis in children in a multicenter cohort. Acad Emerg Med. 2013 Jul;20(7):697-702.
This is a secondary (retrospective analysis) of data from a prospective observational study. The study population was pediatric patients aged 3-10 years presenting with abdominal pain, and those with confounding factors contributing to their pain were excluded. It seeks to clarify the diagnostic value and test characteristics of ultrasound in detecting appendicitis. The authors also compared the sensitivity of ultrasound done at centers that used ultrasound frequently to those that used ultrasound infrequently. Results of the study showed that ultrasound had an overall sensitivity of 72% and a specificity of 97%. Further analysis of the data showed a higher sensitivity (78%) at centers that used ultrasound frequently, when compared with centers that rarely use ultrasound (35%). This study appears to support a previous finding that ultrasound diagnostic reliability improves with the experience of the sonographer and radiologist. It is also noted that ultrasound is only useful in guiding management when the appendix is clearly visualized, raising the sensitivity and specificity of the test to 97% and 92%, respectively. Abdominal pain remains a frequent cause of emergency room presentation, hospitalization, and radiation exposure secondary to CT evaluation. If a non-invasive, non-radiographic study, laboratory value, or clinical tool were available to rule out acute appendicitis without CT or surgery, it would be of incredible medical value. This study is relevant to our practice, but does not change the necessity of CT despite the relative experience of RBC radiologists with ultrasound performance and interpretation.
Submitted by: James Brown
Comments: Hopefully, as more institutions become comfortable using ultrasound for this reason, less CTs will be needed, thus exposing fewer children to unnecessary radiation. Laura Caserta MD

Infectious Disease

Cortese, M et al. Effectiveness of monovalent and pentavalent rotavirus vaccine. Pediatrics. 2013; 132: 25-33.
Since 2008, Rotarix, the monovalent rotavirus vaccine, has been recommended to be given as 2 doses at 2 and 4 months of age. Prior to 2008, Rotateq, the pentavalent rotavirus vaccine was given as 3 doses to all infants. Since Rotarix has been used routinely no studies have assessed the effectiveness of the monovalent vaccine. Children were enrolled in this study if they presented to 1 of the 5 participating hospitals in Georgia and Connecticut with diarrhea of less than 10 days duration between January and June 2010 and 2011 and also were born after the introduction of Rotarix. Stool was tested for rotavirus and immunization records were obtained to ensure Rotarix was given. Case subjects were children whose stool was rotavirus antigen positive. Two control groups were included: 1 group with rotavirus negative stool and 1 group of children selected from an electronic immunization system. Out of 728 children with stool sampled, 165 were rotavirus positive, of whom 123 of the 165 had immunization records available. Vaccine effectiveness was calculated by logistic regression. The monovalent Rotarix vaccine was found to be 91% effective after 2 doses, compared to 92% effectiveness of the pentavalent Rotateq vaccine after 3 doses. After receiving 1 dose, effectiveness was 53%. In children 12-23 months, the monovalent vaccine continued to provide similar protection. The monovalent 2-dose Rotarix vaccine provides similar protection against rotavirus infection in the first 2 years of life as compared to the pentavelent 3-dose Rotateq vaccine.
Submitted by: Brittany Massare
Comments: One wonders if the calculated efficacy of Rotarix was augmented by herd immunity due to preceding use of Rotateq. However, the efficacy estimates reported here for Rotarix are similar to those from European trials, so hopefully the 2-dose monovalent vaccine is the way to go. Lydia Furman MD

Cohen, Robert; Martin, Elvira et al. Probiotics and Prebiotics in Preventing Episodes of Acute Otitis Media in High-risk Children: A Randomized, Double-blind, Placebo-controlled Study. The Pediatric Infectious Disease Journal. 2013; Volume 32(8): 810–814.
Probiotics and prebiotics, which are groups of beneficial endogenously occurring flora, are gaining popularity and wider medical acceptance as methods of treating and preventing recurrent infections. For example when patients have severe GI illness many physicians now recommend taking any number of commercially available products to help restore normal gut flora. Given this, it is natural to wonder if these products would help prevent other common childhood infections, such as AOM. From 2007-2009, researchers in France randomized children (ages 7-13 months) with AOM and high risk of recurrence to receive either pro or pre-biotic supplements or a placebo. By the conclusion of the study, most children in both treatment groups had had at least one recurrence of AOM, and there was no difference between treatment and placebo in the rate of recurrent AOM. Additionally, there was no difference in the rate of other respiratory or GI infections or the need for antibiotic use between the two groups. NP swabs also showed so significant differences in the endogenous flora of the two groups. Although I do not currently routinely recommend probiotic use for my RAP clinic patients, I have been asked about it on a few occasions. My previous stance has been essentially “they might be helpful, so if you want to give them, go ahead.” While perhaps probiotics are helpful for recovery from GI illness, it seems as though they are likely not useful in AOM, an extremely common diagnosis in general pediatrics. As such, given the evidence at this time I will not recommend giving probiotics to children with recurrent AOM.
Submitted by: Kailey Littleton
Comments: Probiotics are certainly gaining a lot of press recently, and it will be interesting to follow studies like this. Laura Caserta MD

Ophthalmology

Chen AJ, Linakis JG, Mello MJ, and Greenberg PB. Epidemiology of infant ocular and periocular injuries from consumer products in the United States, 2001-2008. J AAPOS (2013). 17:239-242.
This is a descriptive analysis of consumer product related eye injury data from the National Electronic Injury Surveillance System, which is a database that identifies unsafe consumer products. The study collected data from 100 random hospitals nationwide that had 24 hour emergency departments. The data that was collected was for infants less than 12 months of age who were treated in an emergency room due to nonfatal consumer product related eye injuries from 2001 to 2008. During this study period, there were about 21,271 emergency room visits for consumer product related eye injuries in infants. 63% of these visits were by infants between 9-12 months of age, 54% were male, and lastly 78% occurred at home. Out of the 6 categories, chemical related injuries were the highest at 46% and household items were second at 24%. Chemical injuries included products such as bleach, bubble solution, cleaners, detergents, paint, and shampoo. Household items included belts, blinds, books, brooms, carpet, erasers, and keys. 37% of these ED eye injury visits were diagnosed as contusions or abrasions, 21% were chemical conjunctivitis and 13% were burns. This study emphasizes the numbers of injuries that children are involved in. This study estimated about 1.8 million consumer product related injuries during their study period in patients 12 months and under. These numbers are staggering. As pediatricians, this study underlines the need for preventive guidance regarding the safety of consumer products.
Submitted by: Diana Yan
Comments: I agree with Dr. Yan’s summary comments. Giving succinct anticipatory guidance about “child proofing” and injury prevention is a challenge, and obviously needs to be tailored to the family’s needs. One wonders how many of these injuries were non-accidental, how many occurred during substitute care, and if there are any industry-wide interventions, such as “childproof” tops for cleaners, paints and shampoo, that would make a meaningful difference. Lydia Furman MD

Pulmonology

Remission and Persistence of Asthma Followed from 7 to 19 Years of Age. M. Andersson, L. Hedman, A. Bjerg, B. Forsberg, B. Lundback, E. Ronmark. Pediatrics Vol 132, #2, Aug 2013.
Parents often ask if their child will outgrow their asthma, which is a common concern among our patient population. Few studies have studied this question. This study prospectively analyzed the incidence of remission of childhood asthma and if any related factors may predict this course. Through an initial family questionnaire 248 children were identified as having asthma in a population in Sweden and were followed up annually through age 19. Asthma remission was defined as no need for asthma medications and no wheeze during the 3years prior to the end of the study. The study found that one in five children (21%) were in remission while 38% had periodic asthma and 41% had persistent asthma. Remission was more commonly seen in males. Sensitization to pets and baseline asthma severity were greater predictors of persistent asthma. Now the next time your patients ask if they can outgrow their asthma, you have some data to point them in the right direction.
Submitted by: Denise Lopez-Domowicz
Comments: Previous studies have shown regional and ethnic differences in the resolution of asthma, and it should also be noted to patients that there is some risk of recurrence in adulthood. Laura Caserta MD

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