Pediatric Research 2014: The Year's Most Interesting Studies

Editor's Note: Keeping up with the relentless body of literature in specialty journals is a daunting task for primary care pediatric providers. Nevertheless, keep up they must; much of this new research affects day-to-day practice and, crucially, early detection and management of numerous conditions that first present in the primary care setting. Medscape spoke with Alan Greene, MD, a Medscape advisor, Adjunct Professor of Pediatrics at Stanford University School of Medicine, and Founder and CEO of DrGreene.com, about the most important studies to date in 2014 and their implications for practice.

What Have We Learned About ASDs?

Medscape: A report earlier this year provided sobering, even frightening, information about the rising prevalence of autism spectrum disorders (ASDs).^[1] The conclusion was that 1 in 68 children aged 8 years (or 14.7 per 1000) had an ASD, compared with a 2012 estimate of 1 in 88 children (11.3 per 1000). Many potential factors have been suggested as causal, including prenatal pesticide exposure,^[2] ASD-specific maternal autoantibodies,^[3] and advanced maternal^[4] and paternal^[5] ages. Other new data suggest that ASDs may be reliably diagnosed in these children as early as 12 months of age,^[6] -- much earlier than the current average age of 4 years at diagnosis. Can you summarize this new information and address the key points for primary care?

Dr. Greene: The new data from the US Centers for Disease Control and Prevention (CDC) on the incidence of ASD diagnoses are profoundly important, because they show a 30% increase in diagnosis just in the past couple of years. And remember, this is during a time when there was no change in diagnostic criteria or data collection methods. Some have challenged the CDC's methodology of looking at medical records instead of examining individual kids; therefore, we cannot be certain that the diagnosis was correct.

Regardless of the exact incidence, we know that kids are receiving diagnoses in unprecedented numbers. According to the CDC, 1 in 42 boys has a diagnosis of ASD.

There are a couple of questions that immediately come to mind. First, where is this coming from? And second, what do we do about it?

In terms of where it's coming from, there have been several very interesting new studies looking at possible causes of autism. A few examine etiologies that occur before the baby is even born.

One study examined the potential of autism-specific maternal autoantibodies to affect the fetal brain. The fetus does not yet have an intact blood/brain barrier to maternal immunoglobulin G. Maternal antibodies cross the placenta. By 13 weeks' gestation, they are already circulating in the baby's blood. By 30 weeks, they're at one half the level they are in the mother's blood. By birth, they exceed maternal levels.

In rodents and nonhuman primates, we know that these antibodies from the mothers bind to specific proteins in the developing brain that are involved in cognition. These include lactate dehydrogenase A and B, stress-induced phosphoprotein 1, collapsin response mediator proteins 1 and 2, and Y box binding protein. So in theory, this could also be a problem in humans.

This big study^[3] that came out of the MIND Institute at the University of California, Davis, looked at the mothers' antibodies and found that 23% of the autistic kids in this study had evidence of these autoantibodies. The striking thing was that there was 99% specificity: If a mother had the antibodies, there was a 99% risk that the baby would end up developing autism at some point in life. This may account for close to one quarter of the cases of autism -- clearly not all cases, but a large percentage. That opens the door for potential treatments that target these antibodies and eliminate them.

Another study examined prenatal risk factors in the same cohort of kids and was also conducted by the MIND Institute.^[2] In California, where the study took place, the exact dates of major pesticide applications commercially on golf courses parks, agricultural field, roadsides, cemeteries, and schools are known. These researchers looked at where women lived during their pregnancy and its proximity to a commercial pesticide application.

There was a direct connection between living within 1 mile of a pesticide application during pregnancy and autism risk. If there was an organophosphate exposure anytime during pregnancy, the risk goes up 60%. If the exposure was to chlorpyrifos, one of the organophosphates, and it was during the second trimester, there was a 230% increase in risk. Chlorpyrifos is a known neurotoxin that in other models has been linked to increased autism.

It looks like the insult often happens before birth and is often out of the parent's control. Obviously, we will need to continue to study both treatments and prevention in the future. But what can we do now?

One of the best things we know to do right now is to diagnose early. Most of the kids in the United States are still diagnosed after the age of 4 years. But we know that screening with the Modified Checklist for Autism in Toddlers-Revise (M-CHAT) in the office setting means that you have a pretty good chance of recognizing these children as early as 18 months of age.

A study presented at the Annual International Meeting for Autism Research was very interesting.^[6] This study looked at repetitive behaviors in kids. In a 12-month-old, repetitive behaviors are normal and quite common. In fact, the normal kids in this study generally exhibited at least 1 and often 2 repetitive behaviors. But the researchers questioned parents about the number of different repetitive behaviors in a group of 12-month-olds, including self-injurious behaviors; head-banging; compulsive behaviors, such as demanding that all steps in an activity be performed in the same order each time; and ritualistic behaviors, such lining up toys or food up a certain way or refusal to eat certain colored foods at certain times. They also asked about restricted behaviors -- really limited areas of activity or interest.

What these researchers found was the kids who had many repetitive behaviors had a much higher risk for autism. For example, children who had 4-8 repetitive behaviors had a risk for autism that was 4 times greater than their peers. This study is not diagnostic, but it does perhaps tell us which kids to pay attention to and could be a great early screening test.

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