Review Article: The Management of Acute Gastroenteritis in Children

Alimentary Pharmacology & Therapeutics

M. Pieścik-Lech, R. Shamir, A. Guarino, H. Szajewska

Aliment Pharmacol Ther. 2013;37(3):289-303

Introduction

Acute gastroenteritis (AGE), characterised by the sudden onset of diarrhoea with or without vomiting, is one of the most common infectious diseases of childhood. In Europe, it is estimated that the incidence of diarrhoea ranges from 0.5 to 1.9 episodes per child per year in children up to 3 years of age.[1] In low- and middle-income countries, while the incidence of acute diarrhoea has declined from 3.4 episodes/child year in 1990 to 2.9 episodes/child year in 2010, the incidence of AGE remains high, especially in infants aged 6–11 months (4.5 episodes/child year).^[2] Moreover, worldwide diarrhoea remains one of the leading causes of mortality among children younger than 5 years.^[3]

In 2008, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society of Paediatric Infectious Diseases (ESPID) developed evidence-based guidelines for the management of AGE for practitioners at all levels of health care – primary care physicians, paediatricians and family physicians – practising in Europe.^[1] In addition, a number of national guidelines have been developed, although their quality varies.^[4] Perhaps the best known among them are those developed by the National Institute for Health and Clinical Excellence (NICE).^[5]

Both ESPGHAN/ESPID and the NICE guidelines largely agree on key issues in the management of AGE. Oral rehydration therapy with a hypotonic solution remains central to the management of AGE. Fast oral rehydration with rapid return to regular food is recommended. 

The routine use of special or diluted formulas is unjustified. Continuation of breastfeeding is strongly recommended. 

The guidelines recommend against the routine use of antibiotics in otherwise healthy children presenting with AGE. 

Regarding drugs, both sets of guidelines recommend against the use of antiemetics, but they strongly emphasise the need for further research. Compared with the NICE guidelines, the ESPGHAN/ESPID guidelines make a stronger recommendation for the use of probiotics for the management of AGE, particularly those with documented efficacy such as Lactobacillus GG and Saccharomyces boulardii. 

The ESPGHAN/ESPID guidelines state that treatment with racecadotril (an enkephalinase inhibitor) may be considered in the management of AGE. Both sets of guidelines state that there is evidence suggesting that smectite (a natural hydrated aluminomagnesium silicate that binds to digestive mucus and has the ability to bind endotoxins and exotoxins, bacteria and rotavirus) is an effective antidiarrhoeal agent, but only the ESPGHAN/ESPID guidelines recommend that the use of smectite may be considered in the management of AGE.

Got (Raw) Milk? Consider the Risk

Medscape Medical News

Janis C. Kelly

February 23, 2012

February 23, 2012 — Researchers from the US Centers for Disease Control and Prevention (CDC) are calling for all states to further restrict or prohibit the sale or distribution of products made from unpasteurized ("raw") milk in the wake of data showing that risk for disease is 150-fold higher after consumption of nonpasteurized dairy products, and that 60% of the resulting outbreaks involve children. CDC epidemiologist Adam J. Langer, DVM, MPH, and colleagues reported their analysis of disease outbreaks from nonpasteurized dairy products in an article published in the March issue of Emerging Infectious Diseases.

Although the distribution of nonpasteurized dairy products in interstate commerce has been prohibited by the US Food and Drug Administration (FDA) since 1987, sale of unpasteurized products within the state where they are produced is regulated by each state. During the time of the study (1993 - 2006), sale of nonpasteurized milk was legal in 25 states.

During that period, the CDC researchers found 121 outbreaks of dairy-related diseases for which the product's pasteurization status was known. This included 73 (60%) outbreaks involving nonpasteurized products, although such products account for less than 1% of total dairy product consumption. In outbreaks involving milk, 82% were from nonpasteurized milk. In outbreaks involving cheese, 42% were from cheese made from unpasteurized milk.

Outbreaks involving nonpasteurized dairy products resulted in 1571 illnesses, with a median of 11 patients, a hospitalization rate of 13%, and 2 deaths. All of the outbreaks from nonpasteurized dairy products were caused by bacteria, most commonly Campylobacter spp (54%), Salmonella spp (13%), and Shiga toxin–producing Escherichia coli (4%), which have animal reservoirs.

Outbreaks involving pasteurized dairy products (which account for 99% of approximately 2.7 trillion pounds of milk consumed during the study period) included 2842 illnesses, resulted in a hospitalization rate of 1%, and caused 1 death. The most common causative agents were norovirus (44%) Salmonellaspp. (20%), and Campylobacter spp (13%). Norovirus has a human reservoir.

"These results suggest that outbreaks caused by nonpasteurized dairy products are probably caused by pathogens in the dairy environment, which would be eliminated by proper pasteurization, and that outbreaks caused by pasteurized dairy products are probably caused by contamination of the products at some point after pasteurization," the authors write.

Of the outbreaks associated with unpasteurized dairy products, 75% occurred in 21 states where it was legal to sell raw milk products during the study period.

"This study shows an association between state laws and the number of outbreaks and illnesses from raw milk products," said Robert Tauxe, MD, MPH, deputy director of the CDC's Division of Foodborne, Waterborne and Environmental Diseases (DFWED). "Restricting the sale of raw milk products is likely to reduce the number of outbreaks and can help keep people healthier. The states that allow sale of raw milk will probably continue to see outbreaks in the future," Dr. Tauxe told Medscape Medical News.

Outbreaks from unpasteurized milk also disproportionately affect people younger than 20 years (60% vs 23% from pasteurized milk). The authors write, "Public health and regulatory authorities are obligated to protect persons who cannot make fully informed decisions (e.g., children) from potential health hazards. Dietary decisions for younger children, in particular, are often made by caregivers. The American Academy of Pediatrics advises against giving nonpasteurized dairy products to children and recommends that pediatricians counsel caregivers against use of these products."

"While some people think that raw milk has more health benefits than pasteurized milk, this study shows that raw milk has great risks, especially for children, who experience more severe illnesses if they get sick," said study coauthor Barbara Mahon, MD, MPH, deputy chief of CDC's DFWED Enteric Diseases Epidemiology Branch. "Parents who have lived through the experience of watching their child fight for their life after drinking raw milk now say that it's just not worth the risk," she told Medscape Medical News.

Of the known sources for 9 of the 15 outbreaks that occurred in states where sale of nonpasteurized dairy products was illegal, 7 (78%) were associated with products obtained directly from the dairy farm, 1 was limited to members of a family who consumed nonpasteurized milk from their own cow, and 1 was associated with products obtained under a "cow shares" communal program, which the CDC report describes as "a scheme used to circumvent state restrictions on commercial sales of nonpasteurized dairy products." Cow share owners argue that they have the legal right to drink raw milk from the cow they partly own.

The CDC researchers also note, "[I]n recent years, foodborne outbreaks involving nonpasteurized dairy products have been reported in association with traditional nonpasteurized products marketed to the growing Hispanic community in the United States."

The researchers warn, "Consumption of nonpasteurized dairy products cannot be considered safe under any circumstances."

In a related development, on February 22 a federal court granted the FDA a permanent injunction preventing Amish farmer Daniel L. Allgyer and his Rainbow Acres Farm from distributing packaged raw milk and raw milk products across state lines from his Pennsylvania farm to participants in a cow share program in the Washington, DC, metropolitan region.

Emerg Infect Dis. 2012;18:385-391. 

Drugs and the Breastfeeding Mother: A New Clinical Report

FDA on Medscape > FDA Expert Interview

Laurie Scudder, DNP, NP, Hari Cheryl Sachs, MD

Disclosures

October 29, 2013

Editor's Note:
Many breastfeeding women are advised to stop taking necessary medications or to discontinue nursing because of potential harmful effects on their infants. The reality is that few medications are contraindicated in breastfeeding mothers.

The American Academy of Pediatrics (AAP) has just released a new clinical report, The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics, to provide guidance on drug exposure and reaffirm the recommendation that most medications and immunizations are safe during lactation. Medscape spoke with lead author and pediatrician Hari Cheryl Sachs, MD, the US Food and Drug Administration (FDA) liaison to the AAP Committee on Drugs, about the key recommendations from the report and resources to assist clinicians in obtaining current information on specific drugs to help guide their advice to breastfeeding women.

Medscape: The key message of this report is that although some drug classes should be avoided or at least used cautiously in lactating women after a careful risk/benefit assessment, many medications can and should be continued. When a healthy nursing mom presents to primary care with a common, mild illness -- such as bacterial sinusitis, migraine, intermittent asthma, or an allergic reaction -- that requires an anti-infective agent, a beta-agonist, an antihistamine, or a triptan, can providers feel comfortable treating this woman and encouraging her to continue nursing?

Dr. Sachs: As stated in the report, not all medications are present in breast milk in clinically significant levels or pose a risk to the nursing infant. The prescribing information (drug label) and LactMed (a drugs and lactation database, also available in a mobile app) will have the information to help a provider decide whether to use a drug in a lactating patient.

Medscape: The report points out that the age of the infant is an important factor in deciding how to treat a mother, because most adverse events associated with drug exposure through breast milk occur in infants younger than 2 months. What other infant factors should clinicians consider when deciding on treatment for a nursing mom?

Dr. Sachs: An important consideration for all drugs is related to the adverse-event profile and properties of the specific drug. Several excellent resources are available to inform clinicians about specific drugs, such as product labeling or LactMed. For example, the FDA recently approved newlabeling information for trimethoprim/sulfamethoxazole (Septra®), emphasizing the need for caution in administering this drug to nursing women, particularly if the infant is jaundiced, ill, stressed, or premature, because of the potential risk for bilirubin displacement and kernicterus.

Medscape: Depression and mood disorders are common in women of childbearing age, and the risks of not treating these women are potentially severe. Data on the long-term safety of psychoactive drugs are limited, yet the report does not recommend advising these women to stop breastfeeding.

Dr. Sachs: Caution is definitely warranted here. As stated in the report, the infant could potentially be exposed to clinically significant levels of these drugs, and the long-term effects are unknown. Decisions about breastfeeding for these patients should be evidence-based. The drug label and LactMed should be consulted for information on drugs that a clinician may be considering.

Medscape: What do you recommend for the care and monitoring of nursing infants whose mothers are being treated with an antidepressant, anxiolytic, or antipsychotic?

Dr. Sachs: Use of these products by nursing women should be discussed with the infant's healthcare provider. Adverse events as well as growth and development should be monitored in these infants. Any adverse events should be reported to the FDA's Adverse Event Reporting System.

Medscape: Treatment of pain is another subject discussed in detail in the report. What is recommended for short-term use in women whose pain is not controlled by over-the-counter analgesics?

Dr. Sachs: Caution is advised for nursing women using narcotic pain relievers because of the potential for adverse effects in nursing infants, and some are not recommended at all for use in nursing women because they are concentrated in breast milk.

Codeine has been associated with rare fatalities in nursing infants. In women with normal codeine metabolism, the amount of codeine (and its active metabolite, morphine) in breast milk is low and related to the dose. However, in ultra-rapid metabolizers, higher-than-expected concentrations of the active metabolite (morphine) may occur in breast milk, and potentially dangerous levels may be reached in breastfed infants.

Thus, the risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and the baby. Close monitoring of mother/infant pairs is recommended when codeine is administered to a nursing woman. The lowest dose should be prescribed for the shortest period to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of toxicity in their infants, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms, such as extreme sleepiness, confusion, or shallow breathing.

Of note, safety labeling changes for extended-release and long-acting opioid analgesics announced by the FDA in September will highlight the risk for neonatal opioid withdrawal syndrome (NOWS) in a boxed warning. Symptoms of NOWS may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

For more information on codeine and other treatment options, see the drug label and LactMed.

Medscape: The report reviewed agents that have been used to stimulate lactation, including dopamine antagonists, such as domperidone, and herbal products, such as fenugreek. What is the bottom line on these agents? Does any evidence support their use?

Dr. Sachs: The FDA issued a warning on domperidone. There is little evidence of benefit with domperidone, and safety information on many of these products is lacking. Nonpharmacologic methods of stimulating lactation are preferred. The report encourages breastfeeding mothers to discuss all products that they take, including herbal products, with their healthcare professionals.

Medscape: The report acknowledges that information in this area changes rapidly, making it impossible for written reports to keep pace with new developments. Drug labels will continue to be an essential source of information. Can you outline some of the key changes in the pregnancy and lactation sections of labeling?

Dr. Sachs: Under the proposed rule, the Pregnancy and Lactation subsections of labeling would each include 3 sections:Risk summary, Clinical considerations, and Data.

In the Pregnancy subsection, the Fetal Risk summary will provide a narrative description based on risk evaluations of human, animal, and pharmacologic data that describe the likelihood that a drug increases the risk for adverse developmental outcomes. The Fetal Risk summary replaces the current pregnancy letter categories (A, B, C, D, X). The Clinical considerations section is intended to further inform prescribing and risk/benefit counseling. Labor and delivery information, when available, will be incorporated into this section. Pregnancy registry information with contact information, when available, must be included in the pregnancy subsection. The Data section will provide a detailed overview of both the human and animal data used to inform the previous sections.

In the Lactation subsection, the Risk summary will summarize what is known and unknown about the amount of drug likely to be present in human milk and any potential effect on breastfeeding infants. The Clinical considerations section will include methods to minimize exposure when applicable, as well as information about monitoring the infant for toxicity or adverse effects. The Data section will provide a detailed overview of available human data used to inform the Risk summary and Clinical considerationssections.

Medscape: What are the best resources for a clinician who needs to access information about a particular pharmacologic agent quickly, in the middle of a busy clinical day?

Dr. Sachs: Drug labeling and LactMed, which I've noted several times, are important resources and are available online at:

• Drugs@FDA (the FDA's database of approved drugs);
• Daily Med (drug information, including FDA labels and package inserts);
• LactMed (drugs and lactation database); and
• LactMed App.

Editor's note: Medscape's Drugs, OTCs & Herbals provides rapid lookup.

Early Onset of Puberty in Girls Linked to Obesity

Medscape Medical News

Joanna Broder

November 04, 2013   Girls in the United States are entering puberty at younger ages than they have in the past, but investigators have not been able to pinpoint the cause. Now, a longitudinal study, published online November 4 in Pediatrics, suggests a higher body mass index (BMI) plays a role in earlier breast development in white, non-Hispanic girls.

"This study demonstrates earlier maturation in white non-Hispanic girls, with greater BMI linked as a major factor," write Frank Biro, MD, the study's lead author and the director of research for adolescent and transition medicine at Cincinnati Children's Hospital Medical Center in Ohio, and colleagues.

"This article adds to studies providing the unsettling findings that the age of onset of breast development, in synch with, though not entirely explained by, the 'obesity epidemic,' has continued to drop," writes Dr. Herman-Giddens, an adjunct professor with the Department of Maternal and Child Health at the Gillings School of Global Public Health, University of North Carolina, Chapel Hill.

The whole distribution of puberty timing has shifted to a younger age, note Dr. Frank and colleagues. The fact that girls are undergoing earlier maturation has important clinical ramifications. For example, girls who reach puberty earlier than their peers may be at increased risk for depression and low self-esteem and be more likely to engage in substance abuse and intercourse at an earlier age than girls who reach puberty later.

In addition, the ripple effects of early maturation extend into adulthood, the authors write, including increased risk of breast and ovarian cancers.

The researchers enrolled 1239 girls from Greater Cincinnati, New York City, and the San Francisco Bay Area. The girls were between the ages of 6 and 8 years at the time of enrollment. Trained clinicians examined the girls at regular intervals for 7 years from 2004 to 2011, assessing breast development through observation and palpitation. They then determined BMI percentiles and z scores, using the 2000 growth charts from the Centers for Disease Control and Prevention.

At baseline, 39% of the black girls had a BMI in the 85th percentile or higher, as did 44% of Hispanic girls, 26% of non-Hispanic white girls, and 12% of Asian girls.

The investigators found that the onset of breast development, as defined by reaching breast stage 2 or greater, differed by clinic site, race/ethnicity, and BMI at baseline.

The mean and median age breast development varied by race and ethnicity. Black girls started developing breasts at a median age of 8.8 years, whereas Hispanic, non-Hispanic white, and Asian girls did so at median ages of 9.3, 9.7, and 9.7 years, respectively.

When the investigators examined timing of breast development and BMI, they found that as the girls' BMI increased above the 50th percentile, the likelihood of earlier breast development increased, relative to girls with a BMI below the 50th percentile (P value for trend = .001). The researchers adjusted for race/ethnicity and site.

In addition, the authors found that the onset of breast development in white girls occurred at younger ages than reported in previous publications but that "black girls continue to experience breast development earlier than white girls." Much of the difference in timing of development in non-Hispanic white girls, between this study and previous ones, is likely a result of the higher BMIs in the current study population, the authors note.

The authors conclude that having a higher BMI is the strongest predictor of earlier onset of stage 2 breast development.

Dr. Herman-Giddens notes that our society may have to live with uncertainty as to what factor or combination of factors is causing girls to start puberty earlier than they did decades ago.

The obesity epidemic is an important factor in the decline in age of onset for puberty in girls, she writes, but she also notes that the study found that BMI accounted for 14.2% of the variance of all covariates in the researchers' model."

Although obesity is implicated as a 'prime driver,' factors involved in these secular changes are far more complex," she writes. "Extensive interacting variables are known to be associated with earlier development in addition to weight and genetics: certain intrauterine conditions and exposures, preschool high-meat diets, dairy products, low fiber intake, isoflavones, high-stress families, absent fathers, certain endocrine disruptors, the microbiome as it influences weight, epigenetics, light exposure, hormone-laced hair products, insulin resistance, activity level, geographical location, and others."

Pediatrics. Published online November 4, 2013.

Nondrug Treatment for Chronic Tension Headache in Teens

Medscape Medical News > Conference News

Fran Lowry

Oct 01, 2013

ORLANDO, Florida — Chronic tension-type headache (CTTH), which may affect up to 20% of teens, can be successfully treated without pharmacologic agents, a new study shows.

A retrospective review of 83 adolescents diagnosed with CTTH found that osteopathic manipulation and instruction in daily mindfulness and the traditional Chinese practice of qi gong was more effective than pharmacologic therapy in relieving their headaches.

"There is nothing in the literature for these kids, who often end up on chronic opioids," lead author Peter Przekop, DO, PhD, from the Betty Ford Center, Rancho Mirage, and Loma Linda University School of Medicine, Loma Linda, California, told Medscape Medical News.

The results were presented here at the American Academy of Pain Management (AAPM) 24th Annual Clinical Meeting.

"I wanted to figure out some way to help them because I see about 60 to 80 teens with this condition a year, and they are miserable. They are not doing well in school, they are not doing well in life. I don't want them on medications, which is always a problem in kids because the brain is changing and developing until 22 to 24 years in females and age 26 in males. Centrally acting medications can affect this development," Dr. Przekop said.

To compare the efficacy of pharmacologic vs nonpharmacologic treatment in teens with CTTH, Dr. Przekop and his team reviewed the charts of 83 adolescents (67 girls and 16 boys) who presented to their outpatient clinic for headache management between 2009 and 2013. Their average age was 15.7 years (range, 13 to 18 years).

"Qi gong is a traditional Chinese practice that aligns breathing, slow, repeated movements and awareness to promote healing," Dr. Przekop explained. "The instruction on how to do mindfulness involves telling the patients to close their eyes, get in touch with what they were feeling inside, breathe, and stop the story going on in their head, to stop the story."There were 2 treatment groups. Group 1 (n = 44 patients) received amitriptyline or gabapentin as daily preventive medication. Group 2 (n = 39 patients) received bimonthly osteopathic manipulation and instruction in daily mindfulness and internal qi gong.

The teens in the experimental group were taught an internal qi gong routine that consisted of 6 simple moves that they practiced each day.

Both groups were assessed at study entry, 3 months, and 6 months to see whether the number and intensity of their headaches changed and whether the intervention affected their general health and quality of life.

Both groups improved, but the improvement was much more dramatic in the group that did qi gong and practiced mindfulness, Dr. Przekop said.

The nonpharmacologic intervention produced better results in headache frequency, headache pain intensity, general health, social activity, and number of tender points in the trapezius, cervical spine, and superior occipital notch than did pharmacologic treatment (P = .001 for all 5 measures).

Over the 6-month period, headache frequency decreased from 23.9 to 16.4 in the pharmacologic treatment group and from 22.3 to 4.9 in the nonpharmacologic group.

"Their perception of their general health improved, and most of these kids actually did quite well," Dr. Przekop said.

"If you meet these kids, they're not doing well in school, they don't have friends, they're staying home, they don't feel good about themselves. That's the thing I wanted to change, and that actually improved," he pointed out. "I think they were able to cope with their overall pain and overall stress and change the way they perceived the world and how they perceived themselves.

"Most pain has a cognitive component, which is how you perceive the world, how you perceive yourself, how you perceive life, and it has an emotional component where these children can't handle negative emotions. That's the thing that really changes with this treatment," he said.

One potential problem is that insurance often will not pay for nonpharmacologic treatment, Dr. Przekop noted.

"These groups were divided pretty much by what insurance would pay. All insurance plans will pay for amitriptyline and gabapentin; few insurances will pay for the other. Some of the kids actually heard that the kids on the non-pharmacologic treatment were improving, and the parents then came and paid cash. It's sad, but that's the state of affairs that we're in now."

Teens Want Control of Their Lives

"Also, the parents are very concerned about beginning their children on these medications, especially over the long run, so this is a great opportunity to begin to say that these non pharmacological things actually do work as good, if not better than medications," he said."I've never seen anything quite like this before, and I think it makes some sense, because when pediatric patients come in they are looking for ways to maintain control of their lives without the use of medications, and if you create the opportunity, many of them will grab on to it," Dr. Hevern, who is also a practitioner at Elliot Pain Management Center in Manchester, New Hampshire, said.

Dr. Przekop and Dr. Hevern have disclosed no relevant financial relationships.

American Academy of Pain Management (AAPM) 24th Annual Clinical Meeting. Abstract #25. Presented September 27, 2013

Weight Loss Advice: It Doesn't Have to Be So Hard

Medscape Diabetes & Endocrinology

An Expert Interview With David L. Katz, MD

David L. Katz, MD, MPH, Laurie Scudder, DNP, NP

Sep 27, 2013

Obesity: How Big Is the Problem?

Medscape: Could you review the epidemiology of obesity, particularly in children, and the impact on type 2 diabetes mellitus (T2DM) over the past 5-10 years? Is the epidemic beginning to abate?

David L. Katz, MD, MPH: For a long time, we have been talking about obesity as epidemic in both adults and children. By definition, that term refers to a condition affecting the population at an unprecedented level, so it doesn't necessarily tell us how many people are affected. It just says it is rising beyond all precedent. Actually, rates in adults have stabilized, and so I think the right way to characterize the prevalence of obesity now is hyperendemic.

It seems to be fixed at a very high level, and there are various sources of information that confirm that, including the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System (BRFSS) at the Centers for Disease Control and Prevention (CDC). These various sources of epidemiologic information and population-level surveys suggest that at least two thirds of the adult population is either overweight or obese nationally. Some surveys have suggested it is as high as 80%.

In the case of children, the figure is lower but actually far more worrisome, because the rates of childhood obesity are unprecedented in history. We really don't know what happens when 30% or more kids are overweight or obese over the course of the lifespan. Consider that the adults who are now dealing with hyperendemic obesity were not subject to hyperendemic or epidemic obesity as children. We can anticipate, then, that with a much higher rate of childhood obesity, these kids, when they grow up, will be experiencing an even higher rate of adult obesity.

In terms of the link to diabetes, we have really seen an epidemic of T2DM, and there the term "epidemic" remains appropriate because the rate of T2DM continues to rise. The CDC has projected that should current trends persist, by or about the middle of this century as many as 1 in 3 Americans could be diabetic. Almost all of that will be T2DM. Since that projection was made, on the basis of computer modeling, we are right on course -- a dire course.

The advent of T2CM in children really is a signature event that characterizes the full toll of epidemic obesity. Those of us who trained in medicine less than 100 years ago learned about 2 kinds of diabetes: juvenile onset, now called type 1, and adult onset, now called type 2. Part of the reason it is now called type 2 is because kids get it now, too. That really never should have happened. The advent of T2DM as a condition in children is a direct by-product of epidemic childhood obesity.

Some good news: We have seen some signs of site-specific stabilization in rates of childhood obesity,and even some slight dips in some regions where a lot of work is being done. We have seen stabilization in the overall rate of adult obesity as well. But one other thing to throw in the mix here is that rates of severe obesity in both adults and children continue to rise briskly.

So as we take stock of the obesity epidemic now, it may no longer serve us adequately to keep asking how many people are overweight or obese, because that number may become relatively stable. What we may now need to start asking is how overweight those people are, because the severity of obesity is worsening.

Medscape: Can you briefly review the recent data on obesity rates from the CDC?

Dr. Katz: The CDC is tracking state-by-state prevalence of obesity on an annual basis, and they issue annual color-coded maps depicting obesity prevalence. Many of us in this field have been following the obesity trends for many years, which are based on self-reported data (Figure).

Medscape: Many experts are suggesting that children born after 2000, new millennium kids, are going to be the first generation in history to have a shorter lifespan than their parents. Is it too simplistic to point at obesity as the sole factor in that? Can you discuss that prediction and what led to that conclusion on the part of many experts?

Dr. Katz: Well, in some ways it is too simplistic to even say with any confidence that this is going to happen, although the analysis that set that discussion in motion was certainly robust. There was a study published in the New England Journal of Medicine in 2005 by Jay Olshansky and colleagues.^[2]Inputting current data on obesity and its effect on longevity, these authors used computer modeling to forecast that life expectancy would level off and potentially decline in the first half of this century.

We have epidemic childhood obesity. We are seeing the advent of what formerly were adult-onset conditions. In addition to T2DM, there has been a proliferation of ever more cardiovascular risk factors in childhood. All of this would conspire not only against life in years, but years of life lived in vital good condition. To some degree, it makes sense to look at the toll of all of this -- ever more risk for ever more chronic disease at ever younger ages -- and conclude that this means a shorter life expectancy.

The problem with that projection from the start was the fact that one of the things we do best in modern medicine is stave off death. We do a very poor job of preserving true vitality. If you look at the epidemiology of the United States, and increasingly much of the world, as was addressed by The Lancet in their Global Burden of Disease Report 2010,^[3] the global burden of chronic disease is huge and rising. We tend to do a fairly poor job of maintaining health, and the epidemiology reflects that we have a lot of chronic disease.

However, we are able to keep people with chronic disease alive. That is where the cutting edge of biomedical advance really comes into play. We have powerful drugs and powerful procedures, and of course, that will only be more so in all probability 10, 20, or 30 years from now, when we might start to see the shortened life expectancy of kids growing up today. We don't know that that will come to pass, but it is still a terrible state of affairs if life expectancy per se is not declining, but health expectancy -- years of life lived in vital good condition -- is on the decline. So I think Dr. Olshansky and the authors involved in that 2005 report would look at what we have learned over the 8 years since then and might not be as sure of that conclusion.

We certainly don't have clear signs of declining life expectancy. It may come to pass, but it may be that medical technology will help us hang on to years of life. What we are clearly losing already is life in years. We are much more confident about that. The basic sentiment in that assertion -- that this is the first generation of kids where we are looking ahead at a shorter life expectancy -- I think is still valid. Whether or not we measure what they are losing in years of life or life in years is what remains to be seen, but clearly there is a lot at stake.

 

Researchers Dissect Link Between Fertility Treatment and Childhood Cancer

Medscape Ob/Gyn 

Peter Kovacs, MD, PhD

DisclosuresOct 02, 2013

Fertility Treatment and Childhood Cancer Risk: A Systematic Meta-analysis

Hargreave M, Jensen A, Toender A, Andersen KK, Kjaer SK
Fertil Steril. 2013;100:150-161

Background

Controlled ovarian stimulation has been available since the 1960s and in vitro fertilization (IVF) since the late 1970s. It is estimated that 4-5 million children have been born following IVF. In developed countries, up to 5% of children born are conceived through IVF.

Since assisted reproductive technology (ART) was introduced, its safety has been questioned and tested. There are immediate risks that are associated with the intervention itself, such as ovarian hyperstimulation; bladder, bowel, and blood vessel injury during retrieval; infections related to the vaginal procedures; and an increased risk for thrombosis.

Numerous studies have evaluated the long-term risks associated with hormone use itself. Most have been reassuring and have found no additional adverse effects with the use of hormones, though infertility itself is a known risk factor for certain gynecologic cancers.

The risk for birth defects following assisted reproduction has also been studied by several groups. While an overall increased risk was seen in ART pregnancies, it is believed that this excess is associated with infertility and the underlying problems rather than the treatment itself.^[2]

Risk for cancer in the offspring conceived through ART is much less studied. In 2005, a meta-analysis found no increased risk for childhood cancer in children conceived via IVF.^[3]

This study is another analysis based on the results of reports published before and after 2005.

Study Summary

Twenty-five studies were included in the analysis. They are all cohort or case-control studies that assessed the association between medically assisted reproduction (stimulation only, insemination, or IVF) and childhood cancer risk. Overall, an increased risk for cancer was seen among those exposed to ART (relative risk [RR], 1.33; 95% confidence interval [CI], 1.08-1.63). When cancer subtypes were evaluated separately, an increased risk was found for hematologic cancers (RR, 1.59; 95% CI, 1.232-1.91) and central nervous system cancers (RR, 1.88; 95% CI, 1.02-3.46). The risk for neuroblastoma, retinoblastoma, and other solid cancers was also higher among those exposed to ART, though the association was based on a small number of cancers.

In their concluding remarks, the authors discussed that while the relative risks show an increased risk, the absolute number of additional cancers is very low. They also mentioned that at this point it is unknown whether the increased risk is associated with infertility or with the technology used to treat it.

Viewpoint

Cancer is the leading cause of death by disease among children under the age of 15 years. Every year, cancer is diagnosed in 1-2 of every 10,000 children. The most common cancers are leukemias, brain tumors, and central nervous system tumors.

While diagnostic and treatment options constantly are improving, cancer is still associated with significant morbidity and mortality. Long-term health may be affected by the treatments even in those who are successfully cured of the disease.

The etiology of childhood cancer is not known, though infectious agents, inherited genetic problems, and exposure to radiation or carcinogens have been all considered. It is also possible that the eggs, sperm, and embryos exposed to in vitro culture conditions are programmed in a way to be at risk for cancer. Epigenetic alterations may activate harmful genes or may suppress genes that are protective. Imprinting defects are believed to play a role in some really rare conditions following ART.^[5]

The possibility that the increased risk is associated with infertility itself, however, cannot be ruled out. In order to answer this, one would need to compare cancer risk in children born to infertile mothers exposed to or not exposed to ART. The authors did point out that only 2 out of 25 studies have taken subfertility into account. Neither of them found an elevated risk for cancer in the children exposed to fertility treatment.

Another study published in 2013 also found an increased relative risk for cancer among children conceived through ART. The 18% relative increase in the risk found by this group would mean 4 additional childhood cancers per 100,000 exposed children.^[8] The absolute risk is low, though, and the couples need to be counseled about both the relative and absolute risks. In addition, it is also important to study how the laboratory procedures may affect the gene expression in the embryos and what steps could be made to avoid these undesired effects. It is already known that the obstetric outcome after ART is not as good as after spontaneous conceptions. It is also known that malformation rates are relatively increased (small absolute increase) following fertility treatment. It is, however, not known to what degree (if at all) the technology is responsible for these findings. The role of infertility as the etiology of these adverse effects needs to be further explored.

Food Allergy Diagnosis and Therapy

Immunotherapy

Where Are We Now?

Aleena Syed, Arunima Kohli1, Kari C Nadeau

Immunotherapy. 2013;5(9):931-944. 

Abstract

Food allergy is a growing worldwide epidemic that adversely effects up to 10% of the population. Causes and risk factors remain unclear and diagnostic methods are imprecise. There is currently no accepted treatment for food allergy. Therefore, there is an imminent need for greater understanding of food allergies, revised diagnostics and development of safe, effective therapies. Oral immunotherapy provides a particularly promising avenue, but is still highly experimental and not ready for clinical use.

Introduction

IgE-mediated food allergy (FA) is a growing problem worldwide. Defined as an immune response to a given food that occurs reproducibly upon exposure, FA affects anywhere from 1 to 10% of the population, with greater prevalence in children (4–6% in the USA vs ~2% in adults). This prevalence has been increasing at a rapid rate, as has been demonstrated by data from the USA, UK, Australia and China. 

Despite this burden, the only currently accepted treatment for FA is complete avoidance of the offending allergen, with epinephrine delivered in the case of accidental ingestions – which occur frequently, even in the most careful patients, and are often undertreated.  As such, FA is a highly stressful condition, generating elevated anxiety in allergic subjects and their families. FA is associated with significantly decreased quality-of-life scores to a degree that is greater than that seen in many other chronic childhood diseases. There is, therefore, an urgent need for an effective therapy for the treatment of FA. Contingent with this is the need for greater understanding of the mechanisms of FA, as well as a need for more precise diagnostics. There is still much that remains unknown, and extensive research in many areas is needed to fully understand this disease and potential treatments. This article aims to address the current state of the field and to speculate on its future.

Acute symptoms include urticaria, flushing, angioedema, abdominal pain, nausea, vomiting, diarrhea, wheezing, coughing and/or bronchospasm, rhinorrhea and hypotension or syncope.

Not all foods are allergenic; in fact, of the over 12,000 food allergens known, only a small number induce allergies. Further questions are raised by spontaneous resolution of FAs. Children usually outgrow allergies to milk, egg, soy and wheat, but not peanut or tree nut allergies.Why this happens, and why only some FAs resolve independently while others remain, is unclear

The environment of the gut is also likely to be crucial. Intestinal permeability is positively associated with increased FA incidence; a study of food-allergic infants demonstrated they had greater intestinal permeability compared with healthy infants, an effect that lasted even after 6 months on an exclusion diet. Likely to be even more important are the microbiota found in the gut. The hygiene hypothesis suggests that changes in the pattern of intestinal colonization during infancy and decreased exposure to infectious agents in childhood are important factors in the development of allergic disease, and may help explain why allergy prevalence is increasing. Antibiotic use and exposure to pets, farms and farm animals have been linked to decreased atopy risk. In addition, differences have been found in gut microbial flora between allergic and nonallergic children, suggesting certain microbes may be more important to sensitization than others.

USPSTF: Blood Pressure Screening Not Useful for Children

Medscape Medical News

Lara C. Pullen, PhD

Oct 07, 2013

The US Preventive Services Task Force (USPSTF) has concluded that "the current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood or adulthood."

The recommendation stands in contrast to the endorsement from the American Academy of Pediatrics of the National High Blood Pressure Education Program 2004 recommendations that children aged 3 years or older have their blood pressure measured at least once at every "health care episode."

The USPSTF published their recommendation statement online October 7 in both the Annals of Internal Medicine andPediatrics . Task force members reviewed studies published since 2003 and could not find any clear evidence that justified blood pressure screening in the general pediatric population.

The recommendations, which are an update to 2003 recommendations, relate specifically to children and teenagers who do not have an underlying health problem and have no signs or symptoms of high blood pressure and encourage clinicians to consider each patient specifically and make an individual decision for each patient.

As the childhood obesity rate has increased, so has the prevalence of high blood pressure in children and teenagers. The prevalence of hypertension among US children and adolescents ranges from 1% to 5%. The prevalence of hypertension among obese children is 11%.

Some clinicians have proposed that screening for hypertension in children and adolescents may allow for interventions to reduce blood pressure, thereby reducing the risk for cardiovascular events and death in adulthood. However, the task force could not find evidence to substantiate this hypothesis.

"We call on the research community to strengthen the evidence base linking screening and treatment of high blood pressure in children and teens to their long-term cardiovascular health," said USPSTF member Kirsten Bibbins-Domingo, MD, PhD, in a USPSTF news release.

Full conflict-of-interest information is available on the journal's Web sites.

Pediatrics. Published online October 7, 2013. Abstract

Ann Intern Med. Published online October 7, 2013. Full tex
t

MMRV - Mumps Measles Rubella Varicella vaccine

Medscape Medical News

ACIP Issues New Guidelines for Use of Combination Measles, Mumps, Rubella, Varicella Vaccine

Laurie Barclay, MD

May 11, 2010

Specific Recommendations for Use

Specific recommendations for use of the MMRV vaccine are as follows:

• Routinely recommended ages for MMRV vaccination continue to be ages 12 to 15 months for the first dose and ages 4 to 6 years for the second dose.
• At ages 12 to 47 months, either measles, mumps, and rubella (MMR) vaccine and varicella vaccine or MMRV vaccine may be used for the first dose of measles, mumps, rubella, and varicella vaccines. Clinicians should inform the parents or caregivers regarding the benefits and risks of both vaccination options. The CDC recommends that MMR vaccine and varicella vaccine be given for the first dose in this age group unless the parent or caregiver expresses a preference for MMRV vaccine.
• For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months - 12 years) and for the first dose at age 48 months or older, the MMRV vaccine is preferred to separate injections of MMR vaccine and varicella vaccine, but provider evaluation, patient preference, and the risk for adverse events should be considered.
• A precaution for MMRV vaccination is a personal history of seizures of any cause or a family history of seizures in a sibling or parent. These children generally should be vaccinated with MMR vaccine and varicella vaccine.

"Studies have not demonstrated that antipyretics (e.g., acetaminophen or ibuprofen) prevent febrile seizures," the report authors conclude. "Vaccination with either MMR vaccine or MMRV vaccine can cause fever and, rarely, febrile seizures. Most fevers and febrile seizures after administration of a measles-containing vaccine occur 5–12 days after vaccination with the first dose."

MMWR Morb Mortal Wkly Rep. 2010;59(RR-3):1-12.

Dexamethasone May Help Atopic Infants With Bronchiolitis

Medscape Medical News

Laurie Barclay, MD

Sep 16, 2013

Oral dexamethasone for 5 days reduced hospital stay for infants with bronchiolitis and eczema or a family history of asthma, according to results from a placebo-controlled trialpublished online September 16 in Pediatrics.

"Because steroid use is known to decrease admission rate and length of emergency stay in children with asthma but failed to do so in bronchiolitis, identifying asthmatic or preasthmatic patients and targeting them with steroid treatment early might improve symptoms and hasten recovery," write Khalid Alansari, MD, FRCPC, from the Division of Pediatric Emergency Medicine, Hamad Medical Corporation in Doha, Qatar, and colleagues. "A shorter stay and possibly a lower chance of needing return visits or subsequent hospitalization are desirable goals of better bronchiolitis therapy."

Therefore, the researchers designed a study to test the addition of dexamethasone to salbutamol in infants at risk for asthma, based on eczema or a family history of asthma in a first-degree relative. They enrolled 200 previously healthy infants, median age 3.5 months, with a diagnosis of bronchiolitis and asthma risk., All were treated with inhaled salbutamol and randomly assigned 1:1 to receive either dexamethasone, 1 mg/kg and then 0.6 mg/kg for 4 more days, or placebo.

Shorter Hospital Stay With Dexamethasone

Infants treated with salbutamol plus dexamethasone had a mean time to readiness for discharge of 18.6 hours (95% confidence interval [CI], 14.9 - 23.1 hours) compared with 27.1 hours (95% CI, 21.8 - 33.8 hours) for infants treated with salbutamol plus placebo. Dexamethasone was therefore associated with a 31% shortening of hospital stay (P = .015). In addition, during infirmary treatment, 5 infants in the placebo group, but none in the dexamethasone group, had to be admitted to intensive care (P = .02).

In the week after discharge, 22 infants in the dexamethasone group and 19 in the control group were readmitted to the short-stay infirmary (P = .9). During 7 days of monitoring, there were no reported hospitalizations or adverse effects.

"Dexamethasone with salbutamol shortened time to readiness for infirmary discharge during bronchiolitis episodes in patients with eczema or a family history of asthma in a first-degree relative," the study authors write. "Infirmary and clinic visits in the subsequent week occurred similarly for the 2 groups."

Limitations of this study include limited detail in safety reporting and lack of measurement of prevalences of patient eczema or atopy in the first-degree family of the bronchiolitis population.

"We speculate that a somewhat more prolonged dosing regimen may also reduce the need for post-discharge visits," the study authors conclude.

This study was sponsored by Hamad Medical Corporation. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online September 16, 2013. Abstract