July 2012 Journal Watch


Diamanti A, Ferretti F, Guglielmi R et al. Thyroid autoimmunity in children with celiac disease: a prospective survey. Arch Dis Child 2011 Nov;96(11):1038-41.
Autoimmune diseases are associated with celiac disease, including autoimmune thyroid diseases. This study looks at the prevalence of thyroid autoimmunity in children with celiac disease who adhere to a gluten-free diet. The authors prospectively followed (for 2 years) 558 patients with biopsy-proven celiac disease on a gluten-free diet and adherence was checked with annual tests of the patients’ anti-transglutaminase (tTG) antibodies. They were matched with 622 controls. Thyroid autoimmunity was defined as having either one or both thyroid antibodies (anti-thyroperoxidase antibody, or TPOAb, and anti-thyroglobulin antibody, or TgAb). If patients had antibodies, thyroid ultrasound and thyroid functions were done to determine if they were euthyroid, subclinically hypothyroid or clinically hypothyroid. This study showed that the prevalence of thyroid autoimmunity was not significantly different in celiac patients on a gluten-free diet than controls. There were no growth restrictions in celiac patients with and without autoimmune thyroid disease. However, the study noted a subsidence of thyroid autoantibodies in about a quarter of all patients with thyroid autoimmunity during follow-up, especially during the first 6 years of a gluten-free diet, suggesting possible regression. For me, this study emphasizes the importance of adhering to a gluten-free diet in patients with celiac disease. I would be less inclined to do routine screening for thyroid disease in celiac patients, especially if they have good compliance. I would only screen for thyroid disease if patients present with clinical symptoms.
Submitted by: Gillian Tam
Comment: There are other recent studies that support this finding. It would still be prudent to screen for thyroid problems if growth is an issue, or as Dr. Tam points out, if the patient has other symptoms suggestive of thyroid disease. LC


Rodday et al. ECG screening for disorders that cause sudden cardiac death in asymptomatic children: a meta-analysis. Pediatrics 2012;129:e999-e1010.
Pediatric sudden cardiac death (SCD) has gained attention with the public and screening has become a controversial topic. Screening works most effectively if preclinical prevalence is high in those screened, if a highly discriminatory screening test is available, if the disease is serious, and if treatment while asymptomatic decreases morbidity and mortality. This article evaluated hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Wolff-Parkinson-White syndrome (WPW), the three most common disorders associated with SCD, and how useful electrocardiogram (ECG) and echocardiogram (echo) were as screening tools. After reviewing articles that examined ECG or echo diagnostic criteria for each disorder, the authors designated the gold standard for HCG as echo, LQTS as gene testing, and WPW as ECG. Next, they evaluated the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), number needed to treat (NNT), false positives, and false negatives of ECG and echo. HCM phenotypic prevalence was 0-170 per 100,000. NPV was about 100% but PPV, NNT, false-positives, and false-negatives varied substantially. LQTS phenotypic prevalence was 1-12 per 100,000. NPV was near 100%, PPV was very low, and NNT was greater than 16,000. WPW phenotypic prevalence was 68-200 per 100,000. No studies reported estimates of sensitivity and specificity. The authors concluded these disorders have very low phenotypic prevalence and screening will lead to many false positives, resulting in additional diagnostic evaluations, unnecessary therapies, physical activity restrictions, and unwarranted anxiety. The authors emphasized that families should be aware that a negative ECG does not definitively exclude risk for SCD because other rare conditions do not have ECG findings. In summary, this article suggests that screening can help exclude disorders causing SCD if negative, but positive findings are less helpful.
Submitted by: Jennifer Szeto
Comment: This information suggests that primary care physicians should not screen children for diseases associated with sudden cardiac death by ordering cardiac echo and ECG. Referral to our pediatric cardiology colleagues for concern, or for chest pain with exertion, appears reasonable at this time. LF


Ellingson CC, Livingston JS, Fanaroff JM. End-of-life decisions in abusive head trauma. Pediatrics March 2012;129(3):541-547.
This article discusses the ethical challenge surrounding victims of abusive head trauma (AHT) and parental rights in end-of-life decisions, specifically when a parent is the accused perpetrator. In our current court system, the medical outcome for the victim of AHT significantly affects the sentencing and potential jail time for the perpetrator, with a 5 – 10 year sentence for abuse charges and up to lifetime for murder charges. When victims are kept alive on life support for a prolonged time it seems to extend the suffering of the already victimized child. Often this is because parents accused of inflicting the harm may have conflict of interest in withdrawing care, submitting them to more intense criminal charges. In addition, the current legal system creates difficulties for ethics committees or legal guardians to supersede the parent’s decision. The article proposed two potential solutions to this problem: 1) recognizing when there is clear and convincing evidence of parental conflict of interest, and allowing court intervention in decision-making at that time; or 2) making sentencing guidelines for cases of suspected AHT so that vegetative state and medical death are treated the same, removing the conflict of interest. The potential for conflict of interest in cases of AHT with suspected parental infliction of harm is great. Medical caretakers must recognize this and work with hospital ethics committees and legal aides to work for the best interests of the children who are victimized. The paper presents an interesting solution to this known problem.
Submitted by: Julie McClave
Comment: These suggestions are innovative, compassionate and in the best interests of the child. Let’s hope the legal system can listen. LF

General Pediatrics

Klein N et al. Measles-containing vaccines and febrile seizures in children ages 4 to 6 years. Pediatrics 2012;129:809-814.
This study looked at 86,750 children between the ages of 4 to 6 years to determine if there was an increased risk of febrile seizures after receiving the MMRV or MMR + V vaccinations. The combined MMR with varicella vaccine (MMRV) was approved in 2005 by the FDA and was then recommended in 2006 by the Advisory Committee on Immunization Practices. Two years later, the MMRV RCA safety monitoring detected a possible increase in seizure risk among toddlers after receiving vaccination. Multiple studies were conducted in 2008 that confirmed that children age 12 to 23 months are at increased risk for seizures after receiving MMRV. This also happens to be peak age at which febrile seizures occur. In 2010, the CDC released recommendations that families should receive MMR + V instead of MMRV if they did not have a strong preference. However, both could be given. Since MMR and varicella vaccines are recommended at 1-2 years of life and 4 to 6 years, these researchers wanted to see if the increase in febrile seizure frequency occurred with the latter age group as well. This study followed children aged 48 to 83 months of age in seven Vaccine Safety Datalink sites between 2000-2008 for 42 days after receiving a measles or varicella-containing vaccine. They tracked post-vaccination seizures and fevers. Overall, only 1 febrile seizure was actually confirmed (95% CI). This study showed that there was no increased risk of febrile seizures among 4 to 6 year olds after receiving MMRV or MMR + V vaccinations. This study is very helpful to general pediatrics practitioners when discussing vaccination risks and side effects with families who may be hesitant to vaccinate.
Submitted by: Lauren Riney
Comment: This is encouraging data. Currently, there is a limited supply of the MMRV vaccine, but it may be more useful in this age group in the future. LC

Heeley-Roy T et al. The prevalence of hypoglycemia in children with vomiting or decreased oral intake and irritability. Pediatric Emergency Care 2012;25(4):333-335.
According to the literature, the greatest predictors of hypoglycemia in young North American children are: female gender, more vomiting than diarrhea, re-hydrating with water (instead of glucose-containing liquids) and neuroglycopenia (neurological symptoms of hypoglycemia: irritability, abdominal pain, headache, visual disturbances, ataxia and poor concentration). This Canadian study examined the prevalence of hypoglycemia in children, aged 1 month to 5 years, presenting to the emergency department with ≥2 vomiting episodes or decreased oral intake and neuroglycopenia. If these symptoms were reported in triage, capillary blood glucose was obtained. If hypoglycemia was present (defined as ≤54 mg/dl), the acuity level was increased and they were treated according to the institution’s hypoglycemia protocol. Children were excluded if they had a known hypoglycemic disorder, severe dehydration, serious altered mental status or recent head trauma. 145 patients were enrolled and 2 were hypoglycemic (prevalence: 1.4%). The mean blood glucose level was 97 mg/dl and the range was 50-210 mg/dl. 9.0% had a low glucose level, ranging from 56-72 mg/dl. The most common discharge diagnoses were (in decreasing order): acute gastroenteritis, viral illness, cold/upper respiratory tract illness/nasal congestion, and acute otitis media. The study data was collected prospectively but was limited by sample size and the subjective nature of symptoms of “decreased oral intake” and “irritable behavior”. Many past studies have shown a high prevalence of hypoglycemia in this age group; however with the low prevalence noted in this limited study, it is not worthwhile to routinely test for hypoglycemia in triage. It would be more prudent to check glucose levels while drawing labs before placing an IV, as it has also been shown that children who require IV hydration are more likely to be hypoglycemic.
Submitted by: Julie Abraham
Comment: I agree that study conclusions are limited by both the “soft” inclusion criteria, as well as the exclusion of severely dehydrated children. A study that enrolls all triaged children at a large and busy ED might provide a better data set for guidelines. LF

Yen C, Tate JE, Steiner CA, et al. Trends in intussusception hospitalizations among US infants before and after implementation of the rotavirus vaccination Program, 2000-2009. JID 2012;206:41-48.
This study examined the rates of intussusception before and after the introduction of two new rotavirus vaccines (RV5 in 2006 and RV1 in 2008). The original rotavirus vaccine was pulled from the market in 1999 due to an association with intussusceptions. This study was a retrospective analysis of the State Inpatient Databases capturing infants aged <12 months via ICD-9 codes for intussusception from 2000-2009. The rates of intussusception were compared between pre-and-post vaccine years. A total of 10,836 cases of intussusception were captured and pre-vaccine rates ranged from 33.1-36.5 cases per 100,000 infants. Post-vaccine rates briefly increased in 2007 to 39 per 100,000 (95% CI 1.04-1.18) but returned to 33.4 and 32.9 in 2008 and 2009. The age-specific analysis demonstrated that among the 6-14 week age group and the 8-11 week subset there was a significant increase in the rate from 10.2 and 6.9 respectively to 13.4 and 11.4 per 100,000 in 2007 (95% CI 1.02-1.69 and 1.08-2.50 respectively). Similar results were found in 2008 but only the 8-11 week age group was significantly increased in 2009. This study is limited due to lack of data regarding vaccine administration and its retrospective nature, but demonstrates a possible increase in intussusception hospitalizations post vaccine release. Given the risks of rotavirus hospitalization and the overall low rates of intussusception even if possibly increased by the vaccination (a distinct possibility raised by this study), I will still continue to recommend the rotavirus vaccine to my patients.
Submitted by: Nathan Beins
Comment: I agree with Dr. Beins’ plan. Important side effects should not be ignored, but the societal benefit of rotavirus vaccination is immense: in comparison to the pre-vaccination era, hospitalization for rotaviral diarrhea decreased by 89% and for all diarrheal disease by 44%, with estimated savings of US$278 million (Eibl Immunotherapy March 2012). LF

Hematology and Oncology

Kristinsson G, Shtivelman S, Hom J, Tunik M. Prevalence of occult anemia in an urban pediatric emergency department. Pediatric Emergency Care 2012;28:313-315.
An estimated 1.6 billion people worldwide have anemia, with the most common etiology being nutritional deficiency. A complete blood count (CBC) is a common test performed in the emergency department (ED). Currently, no standardized approach for management of occult anemia during a pediatric ED visit has been established. The purpose of this study was to determine the prevalence of occult anemia in the ED so that recommendations and guidelines can be made in the future. This is a retrospective cross-sectional study looking at hemoglobin levels of patients from age 1 to 23 years seen in an urban public pediatric ED over a 12 month period. The primary outcome measure was prevalence of occult anemia (i.e. no prior diagnosis) and this stratified by age, sex, and insurance status. 2101 patients had a CBC drawn in the ED. Occult anemia was seen in 13.8% of patients; 14.8% were in preschool, 16.3% were females, 18.5% were uninsured, and 20.7% were female of child-bearing age without insurance. Only 8% of these patients with occult anemia were given the diagnosis at discharge. The authors concluded that anemia is highly prevalent in the urban pediatric ED, but this does not appear to be addressed. Future directions include development of recommendations for this patient population.
Submitted by: Willa Moore
Comment: Since many patients utilize the ED frequently, it would make sense to have a system in place to ensure follow-up when anemia is recognized. Perhaps the use of electronic medical records will help. Any system that is set up should encourage follow up with a primary care physician. LC

Infectious Disease

Garcia S, Mintegi S, Gomez B, Barron J, Pinedo M, Barcena N, Martinez E, Benito J. Is 15 days an appropriate cut-off age for considering serious bacterial infection in the management of febrile infants? The Pediatric Infectious Disease Journal 2012;31: 455-458.
This study is based on data showing recent decreases in rates of serious bacterial infection (SBI) in infants less than three months, mostly thought to be due to improvements in detecting kidney and urinary tract abnormalities prenatally, as well as prophylaxis for Group B Streptococcus (GBS). Some recommendations that this study cites are leaning towards admission of all infants under 28 days old, with some options for outpatient management in those who are older than 28 days old and well appearing. This study sought to find out if this cut-off could be lowered even further, specifically to 15 days. The study is a cross sectional descriptive study with 1575 infants under 3 months of age included, with 307 of these less than 28 days old. Overall there were 311 (19.7%) that were found to have an SBI. In the younger age groups, 8-14 days and 15-21 days, rates were higher, at 31.9 and 33.3% respectively. Infants 22-28 days old had a rate of 22.2%. The article concluded that 15 days is not an acceptable cut-off age for outpatient or less invasive management, but that 21 days may be. Even since the start of my residency there have been a lot of changes in the way people think about “rule out SBI” in infants under 2-3 months of age. I think that this article is a good stepping stone to more studies that need to be done to provide less ambiguous recommendations for what should be done with young infants with fevers. While I am not quite ready to use a cut-off value as low as 21 days, this study to me provides more evidence for using a cut-off of somewhere around 28 days for a more intensive work up in a well appearing infant.
Submitted by: Jackie Hatch-Stein
Comment: Certainly management of fever in the <2-3 months old infant is a moving target, and in-hospital observation without antibiotics may be underutilized. However, the 22.2% rate of SBI cited for the 22-28 day olds is hardly reassuring, and the use of “low risk” criteria in <28 day olds to exclude or identify serious illness has not panned out (Bilavsky et al “A Search for the Holy Grail in the evaluation of febrile neonates aged 28 days or less…” Scand J Infec 2010). We have more work to do! LF

Barrier A, Williams D et al. Frequency of peripherally inserted central catheter complications in children. The Pediatric Infectious Disease Journal 2012;31:519-521.
This study looked at the frequency and types of complications with peripherally inserted central catheters (PICCs) placed in patients <21 years old at a tertiary care pediatric hospital between January and December 2008. They only looked at patients who were immunocompetent and had a PICC placed for parenteral antibiotics. In addition, they evaluated risks associated with complications. PICC complications included central-line associated bloodstream infections, line occlusion, line fracture or leakage, line displacement, localized infection, localized pain, or swelling at the site of the PICC. Overall there were 19.3 complications per 1000 PICC days and 32.8% of all patients with a PICC developed at least one complication. The most common complication was occlusion (34.3%) with 52.1% of the patients requiring tissue plasminogen activation (TPA), 4.2% replacement and 5.6% removal. 40.1% of patients with a complication had a severe complication, defined as infection, removal, or replacement of the PICC. Risk factors for complications included double-lumen PICCs, PICCs placed in the femoral vein, younger age, and greater number of daily doses. Limitations to the study included the fact that they did not control for severity of illness or indication for double-lumen catheters. While PICCs are often medically necessary and allow for parenteral antibiotic administration for prolonged periods of time and at home, it is important to weigh the risks and benefits prior to insertion. The risk factors for complications should be considered before making a decision about placing a PICC and what type of catheter to use.
Submitted by: Tracy Ivy
Comment: This study highlights the fact that PICCs should not be taken lightly, and once placed, need to be monitored closely. LC


Ater D et al. Hypertonic saline and acute wheezing in preschool children. Pediatrics 2012;129(6):e1397-e1403.
Wheezing in preschool children is often caused by rhinovirus infections. The inflammatory cascade of rhinovirus includes thickening mucous production and increases the need for airway clearance in affected children. This study aimed to evaluate whether hypertonic saline versus normal saline would decrease length of stay, admission rates, and clinical severity score in preschool children presenting to the emergency department (ED) with wheezing. This was a double-blind randomized control trial where children in the ED ages 1-6 years with wheezing were given either normal saline or hypertonic (3%) saline along with albuterol for wheezing. Patients were excluded if they were too sick or had a cardiac history. Hypertonic saline was associated with a reduced the length of stay compared to normal saline—median of 2 days (range 0–6) versus 3 days (range 0–5) days (P = .027). Admission rate was also lower in the hypertonic saline—62.2% versus 92%. Due to a small sample size (N=40 in each group), more studies are needed to validate the use of hypertonic saline in this age group. Nebulized hypertonic saline should be considered for possible inclusion in our ED care path.
Submitted by: Andrew Dylag
Comment: LC

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