Neurotoxicity in children: Stemming a ‘silent global pandemic’

Smokestacks-toxins-brain-shutterstock_142235569Maitreyi Mazumdar, MD, MPH, practices pediatric neurology at Boston Children’s Hospital. She leads a research program in Bangladesh that studies the effects of the epidemic of arsenic poisoning on neurological outcomes in children.

Neurodevelopmental disorders, including autism and attention deficit/hyperactivity disorder (ADHD), affect many millions of children and appear to be increasing in frequency worldwide. Improved diagnosis and changes in diagnostic criteria explain a portion of the rise, but not all. In other words, the increase in neurodevelopmental disorders seems to be “real.”

To date, research has mainly invested in finding genetic causes, implicating biological pathways that affect, for example, the formation of synapses and the production of neurotransmitters. Such discoveries improve our understanding of the basic biology of neurodevelopmental disorders and may ultimately lead to new therapies. But genetic variants alone cannot explain the recent rise; if they did, population rates of neurodevelopmental disorders would be expected to stay the same, or even decrease over a 30- to 40-year period, due to affected people likely having fewer children. Instead, reported rates have steadily increased over the past several decades. Something else is going on.

Prominent researchers Philippe Grandjean, MD, and Philip Landrigan, MD, MSc, of the Harvard School of Public Health and the Icahn School of Medicine at Mount Sinai in New York, add an important perspective in a review just published in Lancet Neurology. Calling the situation a “global silent pandemic of neurodevelopmental toxicity,” they argue that chemicals in the environment are important contributors to the rise in neurodevelopmental disorders.

Some substances, including lead, methylmercury, arsenic and polychlorinated biphenyls, are widely accepted to be contributors to brain and nervous system injuries. More recent research has recognized other chemicals, such as those found in insecticides, solvents, flame retardants and plastics, as potential neurotoxicants. In all, Grandjean and Landrigan identify 214 substances recognized to cause neurotoxicity in adults, and 12 substances that show evidence of injury to the developing brains of children. Prenatal exposure to phthalates, for example, has been linked to behaviors that resemble components of autism spectrum disorder. Prenatal exposure to automotive air pollution in California has been linked to an increased risk for autism spectrum disorder.

Developing brains at risk

Unlike adults with known occupational exposures, children’s exposure and injury can go unrecognized for years, and their susceptibility to injury is likely to be greater. Crawling, exploring children tend to come in close contact with their environment, and their bodies are less able to detoxify compounds. Prenatal or early-life exposures can disrupt the process of brain development itself.

Grandjean and Landrigan argue for a new strategy to regulate industrial chemicals, one that takes into account their potential hazards to children’s brains. They propose that all new chemicals should be extensively tested prior to commercial use, in a way includes examination of neurobehavioral functions. They also urge similar testing for chemicals currently in use. In addition, the researchers propose a new international clearinghouse for neurotoxicity, akin to that currently in place for cancer, to coordinate studies and make recommendations. Most notably, they call for eliminating the requirement of absolute proof of toxicity before removing a chemical from the market, adopting instead a precautionary, preventive approach.

We already know that modification of chemical exposures is both possible and cost-effective. In the U.S. alone, the removal of lead from gasoline, paint, toys and water systems has generated an estimated economic benefit that ranges from $110 billion to $318 billion for each annual birth cohort since the 1970s, with a cost-benefit ratio better than that of vaccines. These economic evaluations include estimates of the monetary benefits of preventing cognitive deficits and subsequent increases in educational attainment, earning power and productivity.

A pediatrician call to action

What do these proposals from Grandjean and Landrigan mean for physicians? Physicians by nature are skeptical and historically have been reluctant to consider chemicals in the environment as contributors to neurodevelopmental disorders without definitive “proof” or extensive replication. This reluctance has added to inertia that may leave millions of children at continued risk. We should adopt a precautionary interpretation of the available data that considers the implications of failing to act. Physicians should become familiar with this evidence and support efforts to conduct high-quality and independent research.

In the meantime, we can work with communities to reduce specific exposures (for example, pesticide use on playing fields). We also can support specific pieces of legislation, as the American Academy of Pediatrics recently did for the Safe Chemicals Act of 2013 (S. 696), which would increase the Environmental Protection Agency’s regulatory authority and require manufacturers to conduct more extensive testing.

Pediatricians are in unique and powerful positions to advocate for children’s health. To protect children, we must adopt a new framework that looks closely at the available evidence and emphasizes prevention.