What Factors Influence Linear Growth After Transplantation?

Patient Presentation
A 12-year-old male came to clinic for his health supervision visit. He had a history of living related donor renal transplant at age 10 after a few years of peritoneal dialysis. He was doing well in school and activities. His parents were very happy with his overall health. They expressed concerns about him starting into puberty because of the potential risks for non-adherence with his immunosuppressive medications and also with his growth. The family history showed a predicted mid-parental height between 25-50%.

The pertinent physical exam showed a male with normal vital signs including blood pressure. His height was 10%-25% and weight was 50% and tracking. His abdomen showed several scars and his kidney was palpable without pain/tenderness. He was Tanner 1 for pubertal growth. The diagnosis of a healthy male with a renal transplant was made. The pediatrician discussed that his current height was not significantly different than his predicted height but agreed that seeing endocrinology to discuss potential growth hormone use would be appropriate after the parents said that the nephrologist had suggested an appointment. The pediatrician also talked with the family about supporting their child’s independence over the next few years including medication management. “This is a common concern for families dealing with chronic illnesses. The nephrology team, along with me are here to help you. There are also psychologists who can work with him, and also with you on ways to successfully parent him during adolescence. Just let us know if you think you need help and we’re going to ask about it too,” the pediatrician offered.

Discussion
Growth is a defining characteristic of children. Children are expected to have normal height, weight and head circumference growth velocities for their specific age. A review of mid-parental height determination and other growth parameters can be found here.

For children with chronic illness and organ dysfunction or failure, their bodies cannot be expected to continue to have normal growth and therefore these children often have failure of normal growth for any and all of the growth parameters. For children facing organ failure or high risk or relapsed cancers, organ transplantation can be life-saving, but is not without its own problems including neurocognitive abnormalities, psychosocial dysfunction, endocrine abnormalities, bone abnormalities, primary or secondary malignancy, increased risk of infections and growth abnormalities.

While evaluation of weight and head circumferences are important, many studies have focused on outcomes of final height in children who have undergone transplantation.

Learning Point
Linear growth following organ transplantation appears to be influenced by the following:

  • Genetic potential – mid-parental height should be assessed as obviously this determines target height for the individual.
  • Reasons for the transplant – underlying disorders may change the expected target height, for example certain genetic diseases have short stature and therefore the final height would be less than predicted by mid-parental height. The primary diagnosis is often an important predictor.
  • Organ transplanted – specific organ, and solid organ versus hematopoietic transplant
  • Status before transplant – patients who are more ill (i.e. have spent more time in hospital, have poorer transplanted organ function, have other organ disease) tend to have less catch-up growth however age appears to also influence this. If the child has better height at transplant they tend to have better height after transplant.
  • Age at transplant – younger children often have poorer growth before transplant but have greater catch-up growth than older children and teens
  • Pubertal growth spurt – this appears to play an important role in attainment of final height for patients with transplant as it does for children without them. Some patients have growth hormone deficiency because of their treatment and exogenous growth hormone is sometimes used to assist general linear growth and pubertal growth.
  • Graft function after transplant – patients whose grafts function well (i.e. good overall function and few rejection episodes) tend to have better final heights. Secondary renal or bone dysfunction tends to cause poor final heights.
  • Corticosteroid use – corticosteroid use basically causes poor linear growth. Smaller amounts of corticosteroid tends to improve linear growth.

Overall, final height potentially is improved with smaller amounts of corticosteroids, excellent nutritional support, control of other complications such as rejection or secondary organ dysfunction, and the potential use of growth hormone. All of these can be hard to balance when treating the patient and family. Side effects of immunosuppressive medications can be found here.

Questions for Further Discussion
1. What are risk factors for poor linear growth for patients with chronic diseases and cancer?
2. What type of followup care do patients who have had transplantation need?
3. What type of followup care do adult patients who are survivors of pediatric cancer need?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Organ Transplantation, Kidney Transplantation and Puberty.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Perkins JL, Kunin-Batson AS, Youngren NM, et.al. Long-term follow-up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr Blood Cancer. 2007 Dec;49(7):958-63.

Laster ML, Fine RN. Growth following solid organ transplantation in childhood. Pediatr Transplant. 2014 Mar;18(2):134-41.

Kerkar N, Danialifar T. Changing definitions of successful outcomes in pediatric liver transplantation. Curr Opin Organ Transplant. 2014 Oct;19(5):480-5.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Are Risk Factors for Latex Allergy?

Patient Presentation
A 4-year-old male came to clinic for his health supervision visit. He had a history of lumbar meningomyelocoele not requiring a ventriculoperitoneal shunt. He had a wheelchair for mobility but otherwise was developmentally appropriate and was verbally a precocious child. The past medical history was significant for repair of the meningomyelocoele after birth. He had a history of several urinary tract infections but generally had no problems with his clean intermittent bladder catheterization. The family history was non-contributory. As the physician was preparing to examine the child the mother asked to see the box of gloves. “I know that these are probably latex-free, but better to always check. He’s not latex allergic now and I want to keep it that way,” she said as she double-checked the box confirming they were latex-free.

The pertinent physical exam showed a happy boy sitting in his wheelchair. Vital signs were normal with weight and head circumference trending at the 25%.
His examination was notable for a well-healed scar on his lumbo-sacral area. He had small legs without muscle tone or sensation. The diagnosis of a healthy 4 year old with meningomyelocoele was made. He was current with his immunizations except for seasonal influenza. The physician also confirmed that the live attenuated vaccine did not contain latex.

Discussion
Latex comes from the Hevea brasiliensis plants. There are multiple potentially allergenic polypeptides within the plant’s fluid called Heb b 1-13. True sensitizers are Heb b 1, 5 and 6. Heb b 8 and 12 are cross-reacting proteins.

The type of the latex product and how it is prepared makes a difference in exposure to the latex allergens. Certain extruded latex products such as catheters and rubber stoppers have higher concentrations of true sensitizer allergens. Products made from molds such as gloves have higher concentrations of potential allergens than latex made in sheets such as such as dental dams. Use of powder substances in gloves also increases latex allergen exposure. Cross reactivity with certain foods is called latex-fruit syndrome and includes apples, avocado, chestnuts, banana, kiwi, tomato, bell pepper and carrot. Ficus trees also have some cross-reactivity.

Diagnosis of latex sensitivity and true allergy in the US is usually made by skin prick test conducted in a clinical setting by an allergist. Treatment can include various immunotherapies with the assistance of an allergist. Indications for allergy testing can be found here.

Avoidance of latex products is the best option but it’s difficult to do as latex products are all around us in our environment including clothing (undergarments, socks, bathing suits), sports equipment (balls, grips, masks), condoms, rubber bands or erasers, carpet backing, etc.. In the medical areas, latex in gloves is the one most people think about but other products include the rubber used in stethoscope tubing, rubber hammers, multiple-use vials, syringes, bulb syringes, tourniquets, catheters, bandages, electrodes, heat/cold wraps, impermeable bedding, anesthesia circuits, CPR supplies such as masks and mannequins, surgical clothing, etc. In dentistry, dental dams and orthodontic elastic bands commonly come to mind, but also filling and impression materials may contain it. A list of consumer products that potentially contain latex and some alternatives can be found here.

Questions useful in eliciting a history of latex sensitization or allergy include asking about reactions when exposed to latex balloons or dental dams for dental procedures.

Learning Point
Latex hypersensitivity is about 0.3-4% of the pediatric population. Subpopulations though can be as high as 71%. The highest risk is for patients with spina bifida.

Risk factors for latex allergy and sensitization include:

  • Occupation
    • Food preparation workers
    • Housekeeping personnel
    • Gardener
    • Hairdressers
    • Healthcare workers – surgeon, nursing, laboratory worker, technician, etc. Latex positivity is up to 12% of healthcare workers
    • Others with exposure to frequent gloving
  • Patients who are frequently instrumented or have multiple (N > 5) surgeries
    • Spina bifida – these patients appear to have more sensitization than other similarly exposed patients
    • Urological abnormalities
    • Congenital heart disease
    • Hydrocephaleus
    • Tracheoesophageal fistula
    • Other congenital malformations
  • Having atopy – 1% of atopic children have latex allergy

Questions for Further Discussion
1. What are the 4 types of allergic hypersensitivity?
2. What steps should be taken if a child with latex allergy comes to the clinic or is admitted to the hospital?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Latex Allergy

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

American Latex Allergy Association. Consumer Products. Available from the Internet at http://latexallergyresources.org/consumer-products (cited 210/26/15).

Sampathi V, Lerman J. Case scenario: perioperative latex allergy in children. Anesthesiology. 2011 Mar;114(3):673-80.

Lucas JS, du Toit G, Lloyd K, Sinnott L, Forster D, Austin M, Clark C, Tuthill D, Brathwaite N, Warner J; Science and Research Department, Royal College of Paediatrics and Child Health. The RCPCH care pathway for children with latex allergies: an evidence- and consensus-based national approach. Arch Dis Child. 2011 Nov;96 Suppl 2:i30-3.

Nettis E, Delle Donne P, Di Leo E, Fantini P, Passalacqua G, Bernardini R, Canonica GW, Ferrannini A, Vacca A. Latex immunotherapy: state of the art. Ann Allergy Asthma Immunol. 2012 Sep;109(3):160-5.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

At What Age Does the Risk of Infant Listeria Infection Decrease?

Patient Presentation
A 92-day-old male came to clinic with a fever to 101°F for 24 hours. He appeared well and had no localizing signs on physical examination. He returned to clinic 2 days later with continued fevers up to 102°F. His mother said he was also acting more tired and fussy but consolable. He was drinking and urinating well. His mother said that she had noticed strong smelling urine too. The past medical history showed an uneventful pregnancy and delivery. He had received appropriate health supervision and was current with his immunizations.
The family history was negative for any kidney diseases, hearing problems or genetic diseases. The pertinent physical exam showed an alert male who would get fussy during the examination but calm. His vital signs were normal including his blood pressure taken with an appropriately sized cuff. His temperature was 101.2°F in the office. HEENT was negative. He had no rashes. His abdominal examination was negative. His genitory examination showed a normal male who was uncircumcised. His diaper smelled strongly of urine. The laboratory evaluation showed an elevated white blood cell count of 18.2 x 1000/mm2 with a 32% left shift. His C-reactive protein was 4.8 mg/dl. The urinalyis could not be completed because of a problem in the laboratory but a catheter urine culture was sent. A blood culture was also sent.

The diagnosis of fever without localizing signs with possible febrile urinary tract infection/clinical pyelonephritis was made. The attending physician and the intern discussed potential options for treatment. The intern asked what ages was it appropriate to specifically treat for Listeria. “I know the highest risk is in the first month or so, but I know it certainly can occur after that time. By 90 days I think this infant is at low risk,” the attending answered. He was given intramuscular ceftriaxone and seen the next day. He had done well over the night but was still febrile. His blood culture was negative but the urine culture was growing gram-negative rods. He was given another dose of ceftriaxone. On the second day he returned and had been afebrile for 24 hours. His blood culture continued to be negative and his urine culture was growing E. coli that eventually was shown to be sensitive to cefoxitin. He was treated for 10 days and was awaiting evaluation for a possible urological anatomic abnormality.

Discussion
Neonatal bacterial infections are commonly caused by Group B Streptococcus, enteric gram-negative organisms such as Escherichia coli, coagulase negative Staphylococcus, Listeria monocytogenes and Haemophilus influenza. Infections are usually because of transplacental infection or ascending infection from the mother’s genitourinary tract. Empiric treatment for suspected sepsis for neonates is usually combined IV aminoglycoside and expanded-spectrum penicillin antibiotic therapy in the US and Canada and this combination specifically covers for Listeria.

Listeria monocytogenes was first discovered in 1927 and named in honor of Joseph Lister. It is a ubiquitous, hardy organism that can withstand a wide range of temperatures (multiplying in temperatures from 4-45°C), dessication, low nutrient environments, acidity and salinity. Food borne transmission causes most initial cases as it is obviously difficult to eliminate from the food chain. Healthy individuals may not have symptoms or have mild flu-like or gastrointestinal illness, but can have sepsis or meningitis. The greatest risk is to the elderly, immunocompromised persons, pregnant women and fetuses and newborns of infected women. Listeria infections in these vulnerable populations can affect any organ system including arthritis, conjunctivitis, and endocarditis, but bacteremia/sepsis and central nervous system infections of meningitis and encephalitis and death may occur. For pregnant women, infection is associated with a 10-20% risk of fetal loss and increased risk of premature birth. For premature and term newborns, in addition to bacteremia/sepsis, meningitis, and encephalitis, they can also have pneumonia and granulomatosis infantiseptica. Precautions to potentially prevent Listeria infection are recommended for pregnant women and those considering pregnancy including avoidance of ready to eat deli and luncheon meats or hot dogs (unless reheated to steaming hot), soft cheeses, refrigerated pate or meat spread, refrigerated smoked seafood (such as lox), drinking unpasteurized milk or eating improperly stored food.

Learning Point
Recent data from the United Kingdom covering 1990-2013 found that most cases of Listeria in infants < 1 year were actually in those 1 month but did occur. Of the 5 cases that occurred in 31-90 day olds, these occurred at day 31, 33, 34, 56 and 62. The authors point out that 4 of the 5 had meningitis.

In another international review, 5 cases of Listeria were found in infants 1-3 months old of the total 524 cases of Listeria.

Empiric treatment for potential neonatal or early infant infection from Listeria with antibiotics such as ampicillin or amoxicillin or expanded-spectrum penicillin varies according to location with differing local practices. Some places recommend empiric antibiotic coverage for Listeria up to 3 months of age such as the United Kingdom and others such as in the United States, Listeria may not be empirically covered as early as 4 weeks depending on many clinical factors.

Questions for Further Discussion
1. What are the recommendations for treatment of pregnant women exposed to Listeria or suspected of having an infection?
2. What are the recommendations for treatment for urinary tract infections?
3. What are indications for evaluation of the genitourinary tract for infants and young children with urinary tract infections?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: E. Coli Infections and Listeria Infections.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Okike IO, Lamont RF, Heath PT. Do we really need to worry about Listeria in newborn infants? Pediatr Infect Dis J. 2013 Apr;32(4):405-6.

Arora R, Mahajan P. Evaluation of child with fever without source: review of literature and update. Pediatr Clin North Am. 2013 Oct;60(5):1049-62.

Maertens de Noordhout C, Devleesschauwer B, Angulo FJ, et.al.. The global burden of listeriosis: a systematic review and meta-analysis. Lancet Infect Dis. 2014 Nov;14(11):1073-82.

Anderson-Berry AL. Neonatal Sepsis. eMedicine.
Available from the Internet at http://emedicine.medscape.com/article/978352-overview (rev. 2/11/14, cited 10/26/15).

Okike IO, Awofisayo A, Adak B, Heath PT. Empirical antibiotic cover for Listeria monocytogenes infection beyond the neonatal period: a time for change? Arch Dis Child. 2015 May;100(5):423-5.

Koseki S, Nakamura N, Shiina T. Comparison of desiccation tolerance among Listeria monocytogenes, Escherichia coli O157:H7, Salmonella enterica, and Cronobacter sakazakii in powdered infant formula. J Food Prot. 2015 Jan;78(1):104-10.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

How Much Caffeine is Okay to Consume?

Patient Presentation
A 17-year-old male came to clinic for his sports physical. He was doing well in school and had many friends. He denied any substance use, but did say that he had been using more energy drinks to help him with his weight training program and to stay awake longer at night so he could do his homework. The past medical history showed a healthy teen who had several sprained ankles because of athletics but no head injuries. The family history was positive for attention deficit disorder. The review of systems was negative.

The pertinent physical exam showed a healthy boy with growth parameters in the 50-75%. His examination was negative. The diagnosis of a healthy male was made. The pediatrician discussed with him the reasons for using the energy drinks. He noted that there are many other substances in the energy drinks that could also cause problems and didn’t recommend them or any other dietary supplements. “You are better off following a consistent weight training program and eating a variety of good foods than using the energy drinks or supplements,” he noted. “Let’s talk a bit about where and when you study and also about what you are eating and drinking. Maybe we can find a better combination of food, fluid and sleep that will keep you alert to do your homework too.”

Discussion
Caffeine is a natural alkaloid found in more than 60 plants and is the most, or one of the most, ingested bioactive substances in the world. It is ingested most commonly in beverages (coffee, tea, soft drinks, energy drinks, caffeinated water or alcohol) but is also found in foods, medications, dietary supplements and over-the-counter stimulants. In the US coffee is the major source for adults. The concentration of caffeine depends on many factors such as the coffee species, agricultural practices, drying and storage of the beans, and the roasting, grinding and brewing of the coffee. In the US children ingest caffeine most often in tea and soft drinks. While the overall amount of caffeine intake is generally stable or declining, the use of energy drinks and coffee is increasing especially in the teenage population. The American Academy of Pediatrics recommends that children and teens do not consume energy drinks.

Caffeine impacts on the developing brain are not really known. Teens and children metabolize caffeine faster than adults. Caffeine is absorbed into the circulation usually within 30-45 minutes with peak plasma concentrations at 1-1.5 hours. It is excreted in the renal system but is also resorbed there. Caffeine is mainly metabolized by the cytochrome P450 system of the liver. The half-life is increased in females, pregnancy, preterm neonates, oral contraceptives and other medications, cigarette smoking and liver disease.

Caffeine use has pros and cons, which are listed below:

  • Pros
    • Alertness and attention
    • Concentration
    • Memory consolidation
    • Liver function improvement
    • Weight loss, possible
    • Cancer risk decreased for colorectal, endometrial, liver and prostate
    • Neurological disease risk decreased for Alzheimer’s and Parkinson’s diseases
    • Mortality may be improved with chronic use
  • Cons
    • Alcohol use, increased
    • Anxiety
    • Arrhythmias
    • Bone mineral absorption impaired
    • Death with overdose
    • Diuresis
    • Headache
    • Hypertension
    • Lethargy
    • Restlessness and jitteriness
    • Seizures
    • Sleep, especially inadequate amounts
  • Conflicting Data
    • Diabetes, Type II has decreased risk but other data shows impaired glucose tolerance
    • Cardiovascular, cholesterol and blood pressure problems but other compounds in coffee may have beneficial effects

In caffeine containing foods and beverages there are also other substances which people may have sensitivities to and can have potentially exaggerated responses. People may also mix different foods, beverages and medications which can also cause exaggerated responses. Some of the data is hard to separate out because of concurrent behaviors (e.g. increased alcohol use and caffeine use often occur together) or are intentionally linked. For example, caffeine is used to increase alertness and stave off sleep. This often means that sleep duration is decreased and the quality may be poor. So it can be hard to determine if poor sleep is a separate negative problem caused by caffeine.

Caffeine is prescribed medically for a variety of problems including apnea of prematurity, central nervous system respiratory depression, and migraine headache. Caffeine also causes bronchodilitation and is a derivative of theophylline which can be used for asthma. Pure caffeine is marketed directly to consumers and the US Food and Drug Administration (FDA) notes that at least 2 deaths have occurred because of its use and recommends avoiding these products. The FDA notes that, “A single teaspoon of pure caffeine is roughly equivalent to the amount in 25 cups of coffee.” The FDA does regulate caffeine as a food additive and considers it generally recognized as safe for its intended use specifically with cola-type beverages. The FDA does not require caffeine listed on nutrition food labels because it is not a nutrient. The caffeine concentration is required only on certain dietary supplement labels, but not all of them.

The amounts of caffeine found in common foods and beverages can be found here.

Learning Point
Suggested amounts of caffeine that are generally recognized as safe to consume per day by Health Canada.

  • Children (4-6 years) – < 45 mg/day
  • Children (7-9 years) – < 62.5 mg/day
  • Children (10-12 years) – < 85 mg/day
  • Teens (> 13 years) < 2.5 mg/kg or 100-175 mg/day
  • Adults – < 400 mg/day
  • Pregnancy and Breastfeeding Women- < 300 mg/day

Questions for Further Discussion
1. How much caffeine do you usually consume yourself and why do you consume it?
2. What are the risk factors for caffeine addiction?
3. What are the symptoms of caffeine withdrawal?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Caffeine

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Health Canada. Caffeine in Food. Available from the Internet at http://www.hc-sc.gc.ca/fn-an/securit/addit/caf/food-caf-aliments-eng.php (rev. 2/16/2012, cited 10/19/15).

Gonzalez de Mejia E, Ramirez-Mares MV. Impact of caffeine and coffee on our health. Trends Endocrinol Metab. 2014 Oct;25(10):489-92.

Owens JA, Mindell J, Baylor A. Effect of energy drink and caffeinated beverage consumption on sleep, mood, and performance in children and adolescents. Nutr Rev. 2014 Oct;72 Suppl 1:65-71.

Rosenfeld LS, Mihalov JJ, Carlson SJ, Mattia A. Regulatory status of caffeine in the United States. Nutr Rev. 2014 Oct;72 Suppl 1:23-33.

Wesensten NJ. Legitimacy of concerns about caffeine and energy drink consumption. Nutr Rev. 2014 Oct;72 Suppl 1:78-86.

Carskadon MA, Tarokh L. Developmental changes in sleep biology and potential effects on adolescent behavior and caffeine use. Nutr Rev. 2014 Oct;72 Suppl 1:60-4.

Ahluwalia N, Herrick K. Caffeine intake from food and beverage sources and trends among children and adolescents in the United States: review of national quantitative studies from 1999 to 2011. Adv Nutr. 2015 Jan 15;6(1):102-11.

US Food and Drug Administration. FDA Consumer Advice on Pure Powdered Caffeine. Medscape.
Available from the Internet at http://www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm405787.htm (rev. 9/1/15, cited 10/19/15).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital