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Home – Child Mental Health Blog

Study Finds Link Between In-Utero Acetaminophen Use and Child ADHD

Posted: April 1st, 2014 by David Rettew

A recent study in JAMA Pediatrics caused quite a bit of a stir in finding a possible link between acetaminophen taken during pregnancy and later childhood ADHD.   Acetaminophen has been one of the few medications that has been thought to be pretty safe to use during pregnancy and thus has been the “go to” agent for pain, fever, and other indications, especially given the known risks of some of the alternatives such as NSAIDS.  Now, however, some people aren’t so sure.Tylenol

The study used data from the Danish National Birth Cohort and assessed over 64,000 pregnant mothers.  The amount of acetaminophen use was measured from computer-assisted telephone interviews.  Child behavioral data was collected at age 7 using scores from the Strengths and Difficulties Questionnaire as well as medical records indicating a child took stimulant medications or had an ADHD diagnosis (in this study it was actually ICD hyperkinetic disorder but it is very similar).  Hazard ratios, similar to odds ratios, were calculated to compare the risk of ADHD between acetaminophen exposed and non-exposed mothers, controlling for some potential confounding factors such as maternal infections, inflammation, and maternal mental health.

The study found that majority of mothers did use acetaminophen at some time point during pregnancy.  Compared to mothers who did not use acetaminophen at all, the risk of ADHD in the offspring of mothers who did was significantly elevated, with hazard ratios ranging between 1.13 and 1.37 depending on how ADHD was measured. As an example, elevated scores related to hyperactivity were found in 5.7% of children whose mothers took any acetaminophen during pregnancy versus 4.3% of children who mothers did not. There was also some evidence that higher overall acetaminophen use and use during later pregnancy was associated with higher ADHD risk.

The authors concluded that in utero acetaminophen exposure was associated with increased rates of ADHD or ADHD-like behaviors and they urged further study to verify the findings.  The journal also featured an accompanying editorial which  recommended that  clinical practice not be fundamentally changed from this single non-controlled study.

The media, for the most part, also seemed to get that message and generally did a decent job of not going overboard with their headlines or text.  This was probably good given that everyone seemed to cover the study about a month ago (even I got asked to comment for ABC news).  Clearly, the biggest potential concern is the very real possibility that it is the factors that cause a pregnant mother to take acetaminophen, and not the drug itself, that underlies the link with ADHD.  While the authors took some steps to account for this possibility, they acknowledged that they could not completely control for it.  As there is also some preliminary data linking things like inflammation and infections during pregnancy and child behavioral problems, some restraint prior to changing recommendations seems appropriate.   It is one thing to try something that at best is harmless to see if a health benefit can be obtained (even in the absence of great data), but it is quite another scenario when those actions (or lack of action) may make things worse.   We will have to see, with the message now perhaps being that no medications, over the counter or not, should be taken casually while pregnant.

What might be the mechanism behind this association?  Nobody knows, but the authors did speculate about the possibility that acetaminophen might alter sex or thyroid hormone levels.

 

Reference

Liew Z, et al.  Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders.  JAMA Pediatrics. 2014:online publication.

ADHD Diagnosis Rising Nationally, but not in Vermont

Posted: March 5th, 2014 by David Rettew

The diagnosis of ADHD  has been getting a lot of media attention lately over concerns about possible overdiagnosis and overtreatment.  A recent study from the CDC’s National Survey of Children’s Health now provides important national statistics regarding the prevalence of ADHD, as reported by parents, and the trends over time.  Reports from this survey previously found an increase of 22% from 2003 to 2007 with an overall rate of 9.5%.  At that time, 4.8% of U.S children and adolescents were taking an ADHD medication.  This new study provides information up to 2011.ADHD prevalence by state

The data come from a random-digit-dialed telephone survey of parents that was performed in over 75,000 households using both land lines and mobile phones.  Parents were asked about lifetime and current diagnosis of one of their children as well as about severity, age of onset, and treatment.  The overall response rate was 23.0%.  Analyses were weighted to estimate a total prevalence.

Overall, the rate of ever having ADHD among 4 to 17 year olds nationally was 11% (15.1% for boys, 6.7% for girls), representing 6.4 million children. This rate represents an increase of 42% from 2003 to 2011. Of those will current ADHD, 69% were taking medication for it resulting in an overall medication rate of 6.1%, and increase of 28% from 2007.  About half of children with current ADHD were engaged in some kind of counseling.

There was substantial variation in diagnosis rates and medication treatment between the states with several southern states, such as Arkansas and Kentucky among the highest.  The rate in Vermont was 9.4% which was slightly below the national average and a bit lower than neighboring states (with the exception of New York at 7.7%).  These rates compare to 6.9% in 2003 and 9.9% in 2007 (from the prior CDC report), suggesting that unlike other states, the prevalence in Vermont has not increased from 2007 and may actually be going the other direction.   The 2011 Vermont medication rate was 6.6% which is just above the national average.  Thus, compared to other states, a higher proportion of those diagnosed with ADHD in Vermont are receiving medication treatment.

The authors of the study concluded that there has been a substantial rise in ADHD diagnosis over the past decade with approximately 2 million more children and adolescents receiving the diagnosis now, and most taking medications for it.  This increase, they state, is resulting in an additional burden on the health care system, although the authors don’t do any kind of economic analysis of the costs related to untreated ADHD.

This paper comes soon after a very similar report by McDonald and Jalbert in Psychiatric Times that was previous a topic of this blog.  In that study, the rate of stimulant treatment, using a prescription database, was 2% with Vermont being 34th in the nation.   It is difficult to know exactly how to reconcile these two studies.

While providing very useful information regarding overall statistics, trends, and state differences, it is important to remember that the study has no information regarding the accuracy or appropriateness of the diagnosis or treatment.  Thus, you can expect different people to use these numbers to make different conclusions.   A group here is currently working on some data regarding antipsychotic medications among Vermont prescribers that will shed more light on this important topic.

Reference

Visser et al., Trends in the Parent-Report of Health Care Provider-Diagnosed and Medicated Attention-Deficit/Hyperactivity Disorder: United States, 2003–2011. JAACAP 2014;53:34-46.

Does Atomoxetine Actually Work? Results from a Recent Meta-Analysis

Posted: February 26th, 2014 by David Rettew

Atomoxetine was FDA approved for ADHD in 2002 and touted as a true alternative to stimulants.  While it remains popular today, many clinicians report less than stellar results in treating the core symptoms of ADHD.  This recent review and meta-analysis by Schwartz and Correll examines all randomized controlled studies of atomoxetine versus placebo. While meta-analyses of this medication have been performed in the past, the authors point out that all were industry sponsored.   This one is not, although one of the authors has received financial support from a number of pharmaceutical companies, including  the maker of atomoxetine, StratteraEli Lily.

The authors reviewed and applied meta-analytic summaries of all double-blind randomized controlled trials of atomoxetine for the treatment of ADHD in children. In total, 25 studies were found that met inclusion criteria up until August 2012, which included a total of nearly 4,000 patients. The average trial was almost 9 weeks in length, and all but two were industry funded. The average atomoxetine dose was 1.17 mg/kg and the average age was around 10.

In terms of results, atomoxetine was found to be superior to placebo overall in treating core ADHD symptoms of all types. A total of 44.1% with atomoxetine versus 21.4% on placebo achieved improved scores on ADHD rating scales of at least 40%, resulting in a number needed to treat of 4. At the same time, however, nearly 40% of patients did not respond to the medication.  In other domains such as oppositional defiant symptoms and overall quality of life, improvement with atomoxetine was unimpressive.  Adverse effects including aggression and suicidal ideation did not differ from placebo while other types of side effects were generally mild but higher with atomoxetine.

The authors concluded that atomoxetine appears to be a safe (at least in the short term) and efficacious treatment for pediatric ADHD, relative to placebo, although a sizable number of patients will continue to have significant residual symptoms. The data indicate the possibility of a bimodal response to atomoxetine with many patients responding well and many others have minimal to no improvement. Overall, atomoxetine appears to be about 1/3 to 1/5 less effective than stimulants, with little to guide us in predicting who those patients will be that either respond well or not at all to the medication.

Do these numbers correspond to your own clinical impression?  For me, I don’t think I have found atomoxetine to be as helpful as this article would suggest, although it is important to note that these studies used atomoxetine as a first-line agent while in general practice many of us are turning to atomoxetine only after stimulants have failed.

Reference

Schwartz S & Correll C. Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression. J. Am. Acad. Child Adolesc. Psychiatry, 2014;53(2):174–187

Autism Screening – What Will Happen with the New M-CHAT?

Posted: February 17th, 2014 by David Rettew

When it comes to autism screening for toddlers, the Modified Checklist for Autism (M-CHAT) is one of the most widely used and studied instruments available (and it’s free and dowloadable).   While it’s been shown to have both good sensitivity and specificity, there is always room for improvement.  Thus was born the M-CHAT Revised with Follow-up (M-CHAT-R/F).M-CHAT R

What makes the new scale different is not just some changes in the wording of some of the questions but, perhaps more importantly, how the M-CHAT is scored and categorized.  Now, based on what parents write down on the M-CHAT-R/F, the total score is placed into one of three categories – low, medium, and high risk.  What to do for the low and high risk toddlers is pretty straightforward.  Those at high risk should be sent for a more in-depth autism evaluation right away and those at low risk don’t need further action, other than a repeat M-CHAT-R/F if they are not yet 24 months old.

The middle risk kids are a bit trickier.  Now, the instructions are that primary care clinicians are supposed to go through a series of scripted questions that delve into more detail about those items that are raising a red flag for autism.  Such a process could take about 15 minutes or so and potentially could be done by someone other than the physician.  Based on those questions, another score is generated and if that score is also above the cut-off then the full evaluation is recommended.

A recent study of over 16,000 toddlers who presented for well-child checks at 18 and 24 months of age demonstrated the utility of the new instrument.  Nearly 93% of the initial M-CHAT-R scores were negative, defined as a score of less than 3.  Of those screening positive, 63% of them no longer screened positive with the follow-up assessment.   After establishing an optimal cutoff point of three for the M-CHAT-R and then at least 2 for the follow-up, those who remained positive were found to have a 47.3% chance of being diagnosed with autism, with only 5% of the remaining sample assessed to be developing typically.  This detection rate of autism was found to be superior to that of the original M-CHAT.

The million dollar question in my mind, however, is will this new step for immediate risk really happen in a busy primary care office, and what will occur if it doesn’t?

In the published study, it is important to point out that they didn’t ask the PCPs to do that follow-up piece: the research staff did.  This leaves the open question of how feasible it is to ask the primary care community to do these. Interviews containing scripted questions to help make a diagnosis of various psychiatric disorders have been around for decades and are considered “gold standard” measures that are required in research studies.  However, they are uncommonly used in everyday practice by psychiatrists and even more rarely used in primary care settings.  Consequently, it seems quite likely that many primary care clinics will struggle with this new recommended step.  Am I wrong here?

I was so curious about this aspect that I sent an email to the lead author of the M-CHAT, Diana Robins PhD, at George State University.  She replied quickly and acknowledged that this is looking like a real problem.  In fact, she’s is having trouble finding PCPs willing even to participate in a study about putting the new M-CHAT into practice.

If primary care clinicians decide not to adopt this new follow-up procedure, the instrument could lose some of its discriminative power.  If that happens, a number of things could occur.

  1. Primary care clinicians could just stick to the old M-CHAT (with the loss of the improved instrument resulting in less accurate autism detection)
  2. They could plan to do the follow-up step but often not actually get to it (resulting in a delay of the screening process)
  3. They could group the medium risk kids into the low risk group (which potentially could result in some autistic kids not being formally evaluated until they are older)
  4. They could group the medium risk kids into the high risk group (which could lead to more evaluations and longer waits for kids who would not end up being diagnosed with autism but require formal evaluations to verify this)

None of these options seems ideal and my guess at this point is that the incorporation of the new M-CHAT will be quite slow, especially with this new step in place.  Public health officials interested in autism screening might begin to look for a system that will work without making it too arduous for those who need to implement it.

If you are a primary care clinician that does autism screening, please feel free to comment on what you do now and what you plan to do about the new M-CHAT, if anything.  This one might be worth some follow-up dialogue on how we best should do things around here.

Reference

Robins, DL, et al. Validation of the Modified Checklist for Autism in Toddlers, Revised With Follow-up (M-CHAT-R/F).  Pediatrics 2014;133:37–45

 

 

Child Mental Health Now Versus the Past

Posted: February 3rd, 2014 by David Rettew

Of note, this post is adapted from a similar one that appeared last week in my Psychology Today blog.

From many headlines today, it is easy to get the impression that children and adolescents are struggling more than ever these days.  At the same time, the mental health system designed to help our kids and their families has been under intense criticism for being either completely inaccessible or for being too accessible when it comes to medication treatment.

Churchman photo -sunrise

Image courtesy of John Churchman and www.brickhousestudios.com

Few would argue that there are serious issues to confront right now.  However, it may also be useful to take a step back and look at how levels of problems now compare to the past.  While good statistics in many areas have not been available for that long, what trends are evident for many important metrics of youth mental health may be surprising.  Here are some examples.

Suicide.  The rate of completed youth suicides (we now try to stay away from the phrase “successful” suicide for obvious reasons) has been steadily declining.  The incidence rose steeply, especially for males, from the 1960s until the early 1990s and has been coming down ever since, according to the Center for Disease  Control (CDC).

Teen Pregnancy Rates.  According to the government’s Office of Adolescent Health, the teen pregnancy rate among adolescent females has been cut in half from 1990 to 2012, across many different ethnic groups.

Delinquency.  The number of youth who are incarcerated have dropped from a high of 381 per 100,000 in 1995 to 225 per 100,000 in 2010 according to a report by the Annie E. Casey Foundation.

Substance Use.  The rate of smoking in teens is at an all-time low, according to the Monitoring the Future study that has surveyed substance use for decades.  Cannabis use is also down from peaks in the 1970s, although has been trending up.  Alcohol use in teens is also at historic lows, according to the National Institute of Drug Abuse.

Psychiatric Disorders.  As has been well covered in many venues, there have been significant increases in the rates of many psychiatric disorders, including ADHD, autism, and bipolar disorder.  What is less clear, however, is the degree to which these numbers reflect an actual increase in behavior versus other factors such as an improved detection rates or a lowering of the diagnostic threshold.  A study by Achenbach and coworkers several years ago that looked at quantitative levels of child behavior problems using the same instrument over a 23 year time span found some increases in overall levels from the 1970s to the early 1990s which then began to fall by the end of the millennium.

Child Abuse and Bullying.  Reports from the Crimes Against Children Research Center shows a steady decline in the rate of child abuse since the early 1990s, particularly physical and sexual abuse as well as violent victimization at school.  The reports utilize government data from the National Child Abuse and Neglect Data System.

When it comes to Vermont, many of these metrics look even better in weighing our place relative to other states, especially when it comes to teen pregnancy and youth incarceration. One notable exception, however, is adolescent cannabis use.

There are still many things to work on to help children and their families thrive when it comes of behavioral wellness.  At the same time, however, we also need to recognize that compared to other time periods (particularly the early 1990s for some strange reason), kids today are really not behaving that terribly and now doesn’t look like a terrible time to be a kid.

Reference

Achenbach, T.M., Dumenci, L., & Rescorla, L.A. (2003). Are American children’s problems still getting worse? A 23-year comparison. Journal of Abnormal Child Psychology, 31, 1-11.

Child Psychiatry Phone/Email Consult Service Underused: Help Us Understand Why?

Posted: January 28th, 2014 by David Rettew

For the past year, child psychiatry clinicians at the Vermont Center for Children, Youth, and Families (VCCYF) have been assigned to primary care practices across the state to be available for questions made through phone or email (or this blog).  The program is supported by the Vermont Child Health Improvement Program (VCHIP) and comes at no cost to the primary care practices.Consult program

Many practices have signed up.  However, the number of questions submitted have remained small.  This past quarter, only 19 questions were submitted from 12 primary care clinicians (with only 5 from the previous quarter).  At the same time, the number of requests for in-person consultation has remained relatively constant, reflecting continued need for child psychiatry services.

Those  of us at VCHIP and the VCCYF would like to understand why the service is underutilized in order to try and make any improvements.  Please help us if you are a primary care clinician in Vermont by completing this ONE QUESTION survey by clicking here.

If you would like to enroll of find out more about this program, please contact our project coordinator Eliza Pillard at eliza.pillard@vtmednet.org.

Next Child Psychiatry in Primary Care Conference Friday, May 30

Posted: January 13th, 2014 by David Rettew

pcp conference

Please mark your calendars to attend the 8th annual Child Psychiatry in Primary Care conference to be held Friday May 30, 2014 at the Doubletree Hotel in South Burlington, Vermont.  It promises to be another captivating and practically useful event for primary care clinicians, mental health professionals, and educators.

We plan to have our usual mix of lectures, breakout sessions, and the opportunity to ask case-based questions to a panel of experts.

More information will be coming soon and you can check back at this site and the UVM Continuing Medical Education page.

If there are specific suggestions for topics, please use the comment function here or you can email me at david.rettew@med.uvm.edu.

Vermont 34th in Rate of Stimulant Treatment

Posted: January 5th, 2014 by David Rettew

The popular press has been abuzz with articles on ADHD, with many suggesting that the diagnosis is much overused and that medication treatment is basically a way that affluent parents give their children an academic advantage.   In the midst of all this controversy comes a recent and interesting study in the journal Psychiatric Methods, which compared the rates of stimulant treatment in children and adults across regions, states and counties.

Using an IMS Health database, a total of 24.1 million prescriptions were analyzed, all issued in 2008 and representing over three-quarters of all U.S. pharmacies.   Prevalence rates were calculated using weighted statistics based on U.S. census numbers and regression models were applied to examine potential factors that might be related to the variable rates between different areas.  Of note, the authors looked at sustained stimulant treatment and did not count prescriptions that were filled only briefly.

Overall, a total of 2.5% of children were being treated with stimulant medications nationally with the rate being higher in boys (3.5%) than girls (1.5%).  In addition, 0.7% of adults over age 17 were also receiving these medications.  For children, the lowest stimulant rate was in Alaska (0.4%) while the highest was in Delaware (5.1%).  Vermont came in at 34th at about 2%, while neighboring New Hampshire was 14th which was right after Massachusetts. Regional differences (South, Midwest) were smaller than between neighboring states and counties.  About one-third of the treatment came from psychiatrists. Higher rates of treatment was related in children to an increased supply of pediatricians, lower socioeconomic status of the population, and more funding for special education.

Stimulant Rate in VT

In the discussion, the authors perspective was mainly about access to treatment.  They noted that the prevalence of ADHD is generally cited as between 5-10% which would suggest a large number of children not being diagnosed and treated, especially in particular states and counties.  However, the authors also acknowledged that their data could not directly address the question of under or over-diagnosis.   The finding of stimulants generally being related to families with lower socioeconomic status, however, does suggest that they are not being used simply as a study drug for well-to-do kids. It is also important to note that nonstimulant medications such as atomoxetine as well as nonpharmacological treatment were not included in these analyses.

What to make of Vermont as being towards the bottom of the pack?  I must admit that this result was a bit surprising to me and does not quite square up with data from the Department of Vermont Health Access which found much higher rates, at least among kids with Medicaid.  Furthermore, whether this 2% rate found in this study reflects good and careful prescribing, statewide under-recognition of ADHD, or a mixture of both is difficult to say.   There are wide fluctuations even within our small state related to the density of primary care physicians.  At least in rural areas where access to pediatric care is more difficult, these data would suggest that many struggling children have yet to have their ADHD symptoms diagnosed and treated.

 

Reference

McDonald DC, Jalbert SK.  Geographic Variation and Disparity in Stimulant Treatment of Adults and Children in the United States in 2008.  Psych Services 2013;64(11):1079-1086.

Psychotic Symptoms in Adolescence Common and Appear Dimensionsal

Posted: December 10th, 2013 by David Rettew

While there has been increased appreciation that most symptoms in psychiatry exist along a spectrum or continuum, certain domains have continued to be viewed by many as more binary in nature, meaning that a person generally has the symptom or not.  Psychotic symptoms have generally been one of those areas.  A recent study by Ronald and coworkers that appeared as an advance article from the journal Schizophrenia Bulletin, however, challenges that assertion.

Participants for the study came from the Twins Early Development Study (TEDS) which has been following a community sample from England and Wales.  Over 5000 16-year-old twins and their parents participated. Psychotic symptoms were assessed quantitatively using the self-report Specific Psychotic Experiences Questionnaire (SPEQ) at baseline and, for a subsample, again 9 months later.  The responses from the SPEQ were then analyzed pschometrically  to try and identify key dimensions of psychosis.

In terms of results, psychotic symptoms were found to be quite common.  For example, 15% of the sample reporting hearing voices that commented on what the person was doing or thinking.  Six principle dimensions of psychosis were found namely: paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms.  These domains were found to be relatively distinct with only small to moderate correlations between them. All of these subscales with the exception of grandiosity were found to correlate significantly with levels of anxiety, depression as well as with personality traits such as neuroticism.  Some sex differences were also found such as boys reporting more grandiosity and girls reporting more hallucinations.  The level of psychotic symptoms showed a wide range of variation, with characteristics more like a quantitative trait rather than a discrete “yes or no” presence.

The authors concluded that psychotic symptoms in adolescence are quite heterogeneous and relatively common, with many adolescents endorsing them without high degrees of distress.

It is important to note that this sample was community based and thus, one cannot conclude that similar properties would occur within a clinical sample of youth with psychotic disorders.  The endorsement of psychotic symptoms seemed quite high and may have been due to the main use of a self-report questionnaire.  Specific associations with drug use were not explored.

Reference

Ronald A, et al. Characterization of Psychotic Experiences in Adolescence Using the Specific Psychotic Experiences Questionnaire: Findings From a Study of 5000 16-Year-Old Twins. Shiz Bulletin 2013; Epub ahead of print.

AAP Releases New Child Media Guidelines

Posted: November 20th, 2013 by David Rettew

The American Academy of Pediatrics (AAP) recently published an updated policy statement paper on recommended limits for media usage in kids.  The new report is designed to incorporate the increase of “new media” devices such as mobile phones and computers that are making up an increasingly larger portion of the total time. The trends necessitate that primary care clinicians adapt in the way that they ask about media usage and make recommendations to families.

video games

Photo courtesy of ImageryMajestic / freedigitialphotos.net

The paper cites data from previous studies, chronicling an astonishing amount of media use among youth.  Total time per day using media for entertainment purposes rises from about 8 hours per day in 8-10 year old to a stunning 11 hours or more in teens (it is hard to figure out the math for that one while still leaving time for school).   Over 70% of youth reportedly have a television in their room, not to mention a phone or tablet connected to the internet.  As many parents of teens already know, texting 50 to 100 times per day is now commonplace and ironically, teens are now one of the demographic groups least likely to use phones for voice communication.  Teens also report that they typically have no clear rules about media use from their parents, although parents tend to give a slightly different story.  These concerns are balanced by evidence that the some forms of media can be positive and enhance learning and social interactions.

The guidelines recommend that pediatricians ask two specific questions about media usage with parents namely  1) How much recreational screen time does your child or teenager consume daily? and 2) Is there a TV set or an Internet connected electronic device in the child’s or teenager’s bedroom?  Specific recommendations about media use include the following:

  • Total media use should be less than 2 hours per day
  • Children under age 2 should be discouraged from any media use
  • TVs and internet connected devices should not be in youth’s bedroom
  • Media use should be monitored and discussed
  • Family rules about media use, such as no usage during meals, should be made (and modeled by parents)

Getting less press attention but also contained in the article are also recommendations that primary care clinicians become more actively involved in educational and political groups to advocate for specific policies and laws, such as trying to ban alcohol advertising on television similar to cigarettes.

Following the release of these guidelines, many parents on the internet responded with some skepticism that such limits are realistic.   Indeed, a potential danger is that parents will dismiss the guidelines altogether rather than try to enforce attainable limits even if they fall somewhat short of the specified numbers.  The authors have commented themselves that the recommendations are not meant to be rigidly followed each day but are rather benchmarks that can be flexibly applied.  There is also a bit of a “one size fits all” approach to the guidelines in that no differentiation is given between, for example, a 3- and a 17-year-old.  Public health messages tend to be made as simple as possible to avoid confusion, and often there is a tacit understanding that some degree of customization will be necessary.  If these quite remarkable statistics are true, however, any concerted effort to bring media use into greater balance is a welcome enterprise, with primary care clinicians needed to support children and the families to make healthier choices.

Reference

Strasburger VC, et al. Children, Adolescents, and the Media.  JAMA Pediatrics. 2013;132(5):958-61

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