Category Archives: Pediatrics

“Beyond the bombs: cancer risks of low-dose medical radiation”

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The catchy title comes from a Lancet editorial (Lancet 2012; 380: 455-57); the related article (Lancet 2012; 380: 499-505) details the radiation risk posed by CT scans.

While concerns about imaging radiation exposure have become commonplace, the evidence for the risk has been more in the theoretical realm rather than proven.  That is, the risk projection models were based on studies of survivors of the atomic bombs in Japan.

The retrospective study in Lancet examines 178,604 children who underwent CT between 1985-2002.  Typical followup was 10 years (maximum followup of 23 years).  None of these children had cancer at the time of CT.  The study determined the number of leukemias that developed more than 2 years following CT and brain tumors which occurred more than 5 years after CT.  This lag time was done to avoid any confounding of cancer that may have been present and not detected at time of CT.

Key results:

  • 74 patients developed leukemia and 135 developed brain tumors.  There was a dose-related risk: 0.036/mGy for leukemia and 0.023/mGy for brain tumors.  Thus, the relative risk of leukemia in patients who had at least 30 mGy was 3.18; whereas, brain cancer risk for a cumulative dose of > 50 mGy was 2.82. [1 mGy=1 mSv]
  • If typical doses of CT administered, 2-3 head CTs could triple the risk of a brain tumor and 5-10 head CTs could triple the risk of leukemia.
  • The absolute risk remains low.  In patients less than 10 years, one excess case of leukemia and one brain tumor would be expected for 10,000 head CT scans.

Goal with CT scans:

  1. ALARA: as low as reasonably achievable –for every study.  Newer protocols allow lower radiation doses while preserving good image quality.
  2. Think carefully about each CT.  It is estimated that 20-50% of CTs could be replaced with another type of imaging or not done at all.

For the skeptics about the risk of CT scans, the editorialist concludes that this study confirms “that CT scans almost certainly produce a small cancer risk…we must redouble our efforts to justify and optimize every CT scan.”

Related blog entries:

How much radiation from your CT scanner? | gutsandgrowth

More imaging needed? | gutsandgrowth

Magnetic resonance enterography for Crohn’s disease …

Additional references:

  • -AJR 2001; 176: 289-96. Estimated risks of radiation-induced fatal cancer from pediatric CT
  • -Br J Radiol 2012; 85: 523-28.  Justification of CTs -some not needed
  • -AJR 2010; 194: 868-73.  Lower CT radiation doses in pediatric patients.  ‘Image gently’
  • -Arch Intern Med 2009; 169: 2078-86.

“It is never boring to be a physician”

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…”because patients are so different.  Each has a story to tell.” This is the beginning of an excellent editorial (NEJM 2012; 367: 1350-52).  The editorial helps translate a study about “Phenotypic Heterogeneity” due to copy-number variants (NEJM 2012; 367: 1321-31).  The study itself involved analyzing 32,587 samples from children with developmental delay.  Ultimately, the study focused on 2312 children with 72 copy-number variants.

Both the study and the editorial try to explain why individuals with the same genetic defect have variability in the severity/expression.  Some of the factors include environment, chance, and modifier genes.  Due to the availability of relatively cheap and quick technology, one can sequence all of the 22,000 human genes.  The techonology for this study used microarray-based comparative genomic hybridization to interogate the entire genome.

Copy-number variation refers to changes in the number of genes compared to normal.  Typically, two gene copies are present.  Thus, a deletion or duplications will result in copy-number variants.

In the aforementioned study, investigators found that large copy-number variants contributed to differences in outcomes.  That is, persons with “the same chromosomal abnormality may have very different clinical outcomes” because they a have a second genetic event (copy-number variant elsewhere) that “makes matters worse for them.”

These copy-number variants contribute to learning disabilities.  Large copy-number variants occur in less than 1% of the unaffected population but in 8.6% of children with learning disabilities.  Males are m much more susceptible to have developmental delay due to these copy-number variants and unaffected women are more likely to transmit these copy-number variants.  These gender differences are thought to be due to the fact that males have only a single X chromosome and are more vulnerable to genetic insults as a consequence.

Besides learning disabilities, copy-number variants have been implicated in well-known diseases such as schizophrenia, autism, cardiac disease, and epilepsy.  In addition, well-defined syndromes, like Smith-Magenis syndrome, Williams-Beuren syndrome, Sotos syndrome, and MAPT (17q21.31) deletion syndrome, are also well-recognized as being associated with de novo copy-number variants.

It really is an exciting time to be a physician.  Widely available genetic tests can finally explain a lot of previously unanswered questions.

Lessons on Stature from Asthma Treated with Steroids

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A study of the effects of budesonide for the treatment of asthma should be carefully considered by those of us who treat eosinophilic esophagitis with “topical” steroids; also, this study has applicability to Crohn’s disease patients receiving chronic glucocorticoids.  Mean adult height was 1.2 cm lower in the budesonide-treated asthmatics than in the placebo group (NEJM 2012; 367: 904-12).

This was the main finding at the end of the Childhood Asthma Management Program (CAMP) clinical trial.  This report examined 943 of 1041 (90.6%) participants  who had received either 0.4 mg of budesonide, 16 mg of nedocromil or placebo daily for 4 to 6 years.  Treatment with these agents began between ages 5 to 13.

The reduction in adult height was to similar in adulthood as it was after 2 years of treatment; there was not catch up growth.  With regard to the adult measurements, 96.8% of the adult women were at least 18 years and the adult men were at least 20 years of age.

Other findings:

  • Larger daily dose: each microgram per kilogram was associated with -0.1 cm drop
  • Other risk groups: Hispanic ethnic group, female sex, greater body mass index, longer duration of asthma, and higher Tanner stage at initiation

The authors note that 0.2 mg dosage of budesonide has been shown to be effective to control asthma symptoms in children 5-11 years.  The “lowest effective dose” should be used; “the effect on adult height must be balance against the large and well-established benefit of these drugs in controlling persistent asthma.”

Related links:

Looking better or feeling better in EoE?

Guidelines for Eosinophilic Esophagitis

Choosing topical therapy for EoE

The undiscovered country

Better growth charts for preterm children

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A community-based cohort study from the Netherlands involving 1690 preterm infants (25-36 weeks) and a random sample of 634 full term infants provides a more precise tool for monitoring growth over the first four years of life (J Pediatr 2012; 161: 460-5).

Key findings:

  • The lower the gestational age, the lower the median value for both weight and height.  A quick glance at their tables indicate that infants born at 25 weeks gestation remained on average about 2 kg and 4 cm smaller than full term infants.  Infants born at 32 weeks gestation were on average about 1 kg and 2 cm smaller through the study period.
  • The absolute differences in weight and height were nearly constant, indicating that there was a lack of ‘catch-up’ growth.  At the same time, a child ‘following his own curve’ parallel to growth curve is likely a normal pattern
  • Head circumference at the end of the first year was similar between preterm and term infants
  • Greater variability was noted in boys

While this study did not adjust for maternal height, it is known that short maternal height does correlate with increased likelihood of short offspring.  This is partly mediated by having a small for gestational age birth.  Other limitations of the study included that the cohort was >90% Caucasian, and there was no adjustment for multiple births.

Useful links/references:

  • Growth Charts – Homepage -CDC growth charts
  • Pediatrics 2011; 128: e1187-94.  Growth and predictors of growth restraint in moderately preterm-born children.
  • Pediatrics 2003; 112: e30-8.  Growth of preterm infants during 1st 20 years.

Fontan and PLE

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In my practice, I am asked to give input on patients with Fontan procedure infrequently.  A few recent articles though are a good resource:

  • Nutr Clin Pract 2012; 27: 375-84
  • J Pediatr 2012;161:186-90

Both articles review the physiology and therapies available.  In essence, the Fontan operation establishes a passive connection between the systemic venous return and the pulmonary circulation.  When there are elevated inferior vena cava pressure, this can lead to hepatic dysfunction and protein-losing enteropathy.  The latter is related to engorged intestinal lymphatics, similar to that in congenital intestinal lymphangiectasia.  When lymphatic proteins leak, PLE only develops when the intestinal leak exceeds the patient’s ability to resynthesize lost proteins.

PLE presenting features: edema, diarrhea, bloating, pain, and pleural or pericardial effusions.  PLE places patient at risk for growth failure and associated problems. In more severe cases, hypocalcemia and infections due to lymphopenia can be present.

Potential treatments:

  • Agents that improve heart function -diuretics, pulmonary vasodilators (eg. sildenafil)
  • Corticosteroids including budesonide.  While improvement is common, hypoproteinemia returns after weaning of medication.  Systemic side effects occur even with budesonide.
  • Low molecular weight heparin.  Heparin likely helps by acting as a barrier to large molecules by improving the integrity of the basement membrane
  • Octreotide -has shown some effectiveness as an adjunct to other therapies in small studies
  • Albumin infusions
  • Diet: high protein (≥ 2 g/kg/day), low-fat (<25% of calories from fat), increase medium-chain triglycerides, & sodium-reduced
  • Surgical treatment (eg. atrial baffle fenestration) and cardiac transplantation

The second reference notes that many centers are delaying the Fontan procedure and accepting some degree of hypoxemia.  The problems with this approach include symptoms like headaches and decreased energy levels and the likelihood of developing pulmonary arteriovenous malformations.  Ultimately, the authors hypothesize that biomedical engineers may develop better solutions with miniaturized mechanical support devices to improve pulmonary blood flow.

Additional references:

  • Ann Thorac Surg 2010; 89: 837-42.  Budesonide for Fontan-associated PLE
  • Ann Thorac Surg 2011; 92: 1451-56.  Budesonide for Fontan-associated PLE
  • Congenit Heart Dis 2009; 4: 107-11.  Use of sildenafil for failing Fontan.

Salt for POTS –who benefits?

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Individuals with postural orthostatic tachycardia syndrome (POTS) who have low baseline urinary sodium excretion (<124 mmol/24 hours) were more likely to benefit from sodium supplementation (J Pediatr 2012; 161: 281-4). In this group, “as much as 90% of patients” will improve with salt supplements.

This study from China examined the effects of sodium supplementation in 30 children (20 females, 10 males) as well as in 10 control patients to identify factors which related to therapeutic response.  Criteria for POTS included orthostatic intolerance (without orthostatic hypotension –blood pressure drop >20/10 mm Hg) accompanied by a heart rate increase of >30/min within the first 10 minutes of standing.

Despite normal serum sodium, POTS cohort had baseline 24-hr sodium excretion of 117 ± 59 compared with control of 194 ± 91.  POTS sodium-responders were similar in all aspects at baseline except for lower sodium excretion: 85 ± 35 compared to 150 ± 51 for POTS sodium-nonresponders.

The discussion reviews the theoretical reasons for POTS response to sodium (e.g.. ‘relative hypovolemia’) and points out that there are several subtypes, including ‘hypovolemic,’ hyper-adrenergic,’ and ‘autoimmune.’ Salt supplementation which has been shown to be effective only in the pediatric population targets the hypovolemic subset.

Limitations:

  • Small sample size
  • Lower sodium excreters had more symptoms at baseline & therefore may have led to bias as well

Additional references:

  • -J Pediatr 2011; 158: 20 (pg 4 editorial). n=53. GI pain in 75%, nausea/vomiting in large fraction, sleeping problems in 98%, headache, syncope, urinary symptoms. May have poor stomach emptying due to autonomic dysfunction
  • -J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):314-8. Gisela Chelimsky  “Gastric Electrical Activity Becomes Abnormal in the Upright Position in Patients With Postural Tachycardia Syndrome”
  • -J Pediatr 2011; 158: 499. Orthostatic hypotension can be treated physically: gripping hands for 15 secs before rising, lower body muscle contraction (eg pumping calf muscles/tensing legs), squatting…

Why Pertusis is resurgent –it’s not what you think

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What are the reasons why pertusis, a vaccine-preventable disease, is epidemic?

According to an editorial by James Cherry (NEJM 2012; 367: 785-87), there are four main reasons.

  • 1) Increased awareness
  • 2) Easier detection with PCR assays
  • 3) Increased use of less potent vaccines, mainly DTaP
  • 4) Possible genetic changes in B pertusis

Useful epidemiology information:

  • 13-20% of adolescents and adults with prolonged cough have B pertusis.
  • Lowest incidence was reported in 1973: 1 per 100,000.
  • In prevaccine era, B pertusis had pattern of epidemics every 2 to 5 years, with peak incidence of 157 per 100,000.
  • In 2010, incidence was 9 per 100,000
  • Neither infection or immunization provides lifelong immunity

His recommendations/conclusions:

  • We need to use the vaccines we have.  This is necessary to avoid the ‘frightening rates of complications and death’ associated with pertusis in infants.
  • Consider starting immunization at an earlier age –1st three doses could be completed by 3 months of age
  • Improved vaccines are needed

Related blog entries:

Protecting the most vulnerable

Hepatitis A vaccine immunity –will it last?

How to stop HBV vertical transmission

Epidemic of Prescription Drug Overdoses

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More information on the epidemic of drug overdoses: MMWR 2012: 61: 10-13.

In 2007, in U.S. one death due to unintentional drug overdose occurred every 19 minutes (27,000 cases), primarily due to opioid analgesics.  In addition, for every death, there were nine persons admitted for drug treatment, and 35 emergency room visits.

The escalating drug use can be quantified.  In 1997, drug distribution through pharmacies delivered the equivalent of 96 mg of morphine per person whereas in 2007 the amount was 700 mg per person; 700 mg is enough for every person in U.S. to receive a three-week course of Vicodin (hydrocodone/acetaminophen 5mg q4 hours).

Only 10% of these patients were seeking care from multiple doctors; yet this 10% accounted for 40% of the cases of overdosage.

Prevention strategies:

  • Prescription data to prevent doctor shopping & reduce inappropriate use of opioids/selling excessive opioid prescriptions
  • Enforcing laws against ‘pill mills’
  • Improve medical practice in prescribing opioids

Additional references/previous blog entries:

Epidemic: Responding to America’s Prescription Drug Abuse Crisis  Whitehouse plan

Pediatric pharmaceutical poisoning

Deadly consequences of pain management

Why “therapeutic dose” of codeine can kill

What is resistin?

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Resistin is a cysteine-rich protein which is often elevated in chronic renal disease and has been associated with increased risk for cardiovascular disease (CVD) (J Pediatr 2012; 161: 276-80).  It is expressed primarily in macrophages and stimulates the production of interleukin 6, and tumor necrosis factor α (TNF-α).

The cited study examined whether resistin was associated with renal function and inflammatory markers in 319 children from the Chronic Kidney Disease in Children (CKiD) cohort.  The CKiD study is a longitudinal observational study from 46 pediatric nephrology centers in North America.  For this study, the glomerular filtration rate (GFR) had to between 30-90 mL/min/1.73 m-squared.

Findings:

  • Serum resistin was significantly associated with elevated inflammatory cytokines IL-6, IL-10, and tumor necrosis factor.
  • Resistin levels were negatively correlated with GFR.  The authors state that decreased clearance may not be the only reason for higher resistin levels as chronic kidney disease is a state of chronic inflammation and resistin may be involved in these processes.
  • Resistin also was independently associated with pubertal status

Is it possible to avoid allergic food reactions?

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In subjects with known food reactions, avoiding food ingestions is quite difficult (Pediatrics 2012; 130: e26-e32).

This study enrolled 512 children at ages 3-15 months and followed them for a median of 35.5 months.  Patients had to have positive skin prick test to milk or egg in addition to either a history consistent with an IgE-mediated food reaction to milk or egg or a history of moderate-to-severe atopic dermatitis.

Key findings:

  • High rate of reactions: 1171 reactions reported in 367 (72%) of subjects.
  • Most reactions were attributed to lack of vigilance, like not checking ingredients
  • Parents most frequently were the providers at time of incident (36%); however, about half of all allergic reactions were attributed to other providers (eg. grandparents, teachers)
  • Of severe reactions (n=134, 11%), only 30% were treated with epinephrine. Almost all severe reactions were due to ingestions (95%) rather than skin or inhalation exposures.

Bottom line: More work is needed to prevent these reactions and to improve the treatment when they occur.

Save a life with free allergy education

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