Environmental Influences on Neurodevelopment: An Overview by I. Leslie Rubin, MD

This essay is in response to the question: How does the environment influence brain development? What are the exposures of greatest concern? What is the latest science and how can we translate that science into protective public health policy? 

Environmental Influences on Neurodevelopment: An Overview  By I. Leslie Rubin, MD http://www.psr.org/environment-and-health/environmental-health-policy-institute/responses/environmental-influences-on-neurodevelopment.html

Brain development and vulnerability – The human brain is so complex that is takes almost two decades before it stops growing. What begins as a neural tube in the early embryonic stage of development evolves into a complex set of networks that serve as a coordinating center for the maintenance of organ function and for the physical and physiological processes that assure survival and success of the individual and the species.

Early fetal brain development is critically dependent on proliferation of cells – neurons – which then elaborate axons and dendrites to form the network of connections and communications between cells. The process of neuronal cell migration in the brain not only enhances the number and complexity of connections between the cells, it also creates the infrastructural spatial relationships that optimize function. The next step in the process of brain growth and development is the insulation of fatty tissue on the nerve extensions to enhance the speed of transmission of impulses between the neurons.

Any element of the elaborately sequenced choreography of brain development at the microarchitectural level and in its fundamental neurochemistry can be enhanced by adequate nutrition, nurturing and optimal environmental factors as well as interrupted or disrupted by adverse environmental factors.

Environmental factors affecting brain development and function

Environmental factors can have an effect at any time in the process of brain development, however, the earlier the stage of brain development the greater will be the impact on brain structure and function. Thus, the fetal brain is most vulnerable to chemical and infectious agents present in the maternal circulatory system.

Intrauterine infections

A dramatic example of an intrauterine infection occurred during the Rubella Epidemic of 1963-1965. Babies born to mothers who contracted Rubella during pregnancy had significant brain damage with consequent functional complications such as intellectual disabilities, visual impairment and autistic behaviors. The degree and nature of the impact was related in large part to the timing of the infection – the earlier in pregnancy that a mother was infected, the greater the degree of brain damage and neurological complications. As a result of this natural disaster, we learned not only about the vulnerability of the fetus to maternal infections, but that we could develop strategies to prevent these undesirable consequences through immunization.

Neurotoxins during pregnancy

An example of intrauterine exposure to a neurotoxin can be seen in the case of alcohol. Although not traditionally considered an environmental toxin to those of us in the outside world, to the fetus alcohol is a powerful environmental neurotoxin. We have learned from our experience with intrauterine alcohol exposure that the timing and amount of the exposure to alcohol can have serious lifelong consequences that range from mild to severe. We also learned that we can prevent this exposure by education as well as by influencing public policy. We now have labels on bottles of alcoholic beverages that warn women of the risks of alcohol to the fetus during pregnancy.

Another serious neurotoxin to the fetus is tobacco smoke. Although the impact of tobacco smoke on the developing brain of the fetus is not as dramatic as Rubella or alcohol, we have learned that fetal exposure to maternal smoking during pregnancy can result in reduced birth weight and prematurity with its associated morbidities, as well as on brain function resulting in significant impairment in cognitive function. As with alcohol, we have developed strategies to prevent this exposure by educating pregnant mothers and their families against smoking, and tobacco products now carry warning labels that are designed to deter potential smokers.

We are also aware of the adverse effects on brain development of infants exposed to a variety of illegal drugs during pregnancy such as cocaine, heroin, methamphetamine, PCP, and LSD. Obviously it is critical to prevent substance abuse especially during pregnancy because it not only affects the user, but the unborn baby can suffer lifelong consequences.

Medications can also affect brain development – some of them resulting in physical characteristics as well, such as fetal hydantoin syndrome, with distinct physical and neurodevelopmental characteristics associated with exposure to the anticonvulsant medication phenytoin (Dilantin), which the mother had to take to prevent seizures. There are a number of other medications that affect the fetus in similar ways. This awareness has led to a strict policy that all drugs in the pharmacopeia are tested for, and have a statement about, safety during pregnancy.

Heavy metal exposure during pregnancy

In the 1950s, in a small Japanese fishing village on Minamata Bay, there was an epidemic of children born with cerebral palsy, convulsions, intellectual disabilities, and visual and hearing impairment. The cause was discovered to be methyl mercury which had found its way into the food cycle of fish that were eaten by the local people. About 27 tons of methyl mercury had been discharged into the bay over a period of 37 years by a petrochemical and plastics company and it has been estimated that as many as 50,000 people have been poisoned by the mercury. We learned many lessons from this disaster, not the least of which was that industrial plants have toxic waste and that we need to protect citizens from this through regulation of how factories dispose of their waste. Although the clinical picture of the children affected in Minamata Bay was dramatic because of the very high level of methyl mercury, we know that low levels of methyl mercury are also toxic to the developing fetal brain. As a result of the cumulative effect of decades of discharge of industrial waste into our waters, there has been a bioaccumulation of mercury in fish in our waterways. Advisories have been developed to reduce consumption of fish that would be more likely to contain higher amounts of mercury. This is especially important for pregnant women and women of childbearing age.

Convincing evidence is emerging that exposure during pregnancy to heavy metal toxins such as lead and mercury, to chemical agents such as PCBs, and to organic compounds such as pesticides and herbicides can affect brain development and result in significant intellectual or learning disabilities, muscle tone and motor coordination difficulties, as well as behavior problems such as ADHD and Autism.

In a two-year study involving five independent research laboratories in the United States, Canada, and the Netherlands, researchers found up to 232 toxic chemicals in the umbilical cord blood of 10 babies studied. These findings demonstrate that the chemicals were present during intrauterine life when the brain was in the critical phases of neuronal proliferation and migration and therefore most vulnerable to even small amounts of toxin. These findings create a great challenge for all members of our society and our global community to understand where they came from, what they are doing and what to do about them.

Lessons from lead

It is helpful to examine lead as a prototype of an environmental toxin that can harm the brain and cause significant neurodevelopmental disorders. In the early and middle part of the 20^th Century, lead was a common ingredient in gasoline which resulted in exhaust fumes that filled the air with lead. Lead was also a common ingredient in paint which was found in the interior and exterior of all houses. Paint would chip and peel and if sanded filled the air and eventually the soil with lead. Lead was also present in water pipes, contaminating the drinking water. Lead toxicity in children resulting in significant brain damage was not uncommon. Lead levels of over 60 micrograms per deciliter were considered toxic enough to require chelation; lead levels in children who were acutely poisoned often exceeded 60. Thanks to the efforts of researchers and advocates, legislation was passed that banned lead from gasoline and paint and as a result the likelihood of acute lead toxicity has been dramatically reduced. Whereas in those “olden days” a lead level of 40 or less was considered satisfactory, today we have come to recognize that a lead level of 10 can have adverse effects on the brain and we are even worried about lead levels of 5 as placing a child at risk for some degree of cerebral impairment manifesting in attention deficit disorder, learning disabilities, and/or behavior problems.

Although the risk of lead toxicity has been dramatically reduced as a result of the removal from paint and gasoline, children are still at risk, especially children who grow up in poverty or in other parts of the world. Children who are poor are more likely to have lead toxicity and to have permanent difficulties as a reflection of brain damage.  Kosovo Gypsy children, who were displaced by the war in that region a decade ago, were relocated near a toxic waste dump site where lead abounded and suffered severe lead toxicity. In northern Nigeria, children were put to work extracting precious metals from illegal mines, and, in the process, were exposed to high levels of lead, resulting in significant morbidity and mortality. Today, in regulated countries like the US, lead continues to turn up in various ways, e.g. in paint on toys from China, in home remedies for various ailments (even for crying babies), in some pottery, and in some cosmetics. The lesson is that we can never assume lead has been taken care of through the bans of lead in gasoline and paint. We need to be vigilant at all times.

Other, less common, metals can also cause disruptions in brain metabolism and function. Many are both nutrients andneurotoxicants, such as iron, zinc, copper, and manganese. Other metals, such as lead and cadmium, operate by substituting for the necessary metabolic ions and, thereby, disrupt the normal metabolism and adversely affect brain function and development.

Other environmental factors

Screen time

There are environmental exposures, besides chemicals, that can have negative consequences on brain function. Commonly today, children are exposed to a large amount of television viewing. As with some chemicals, short term exposure to low doses may not have permanent consequences, but exposure to large doses over long periods of time can certainly have long term effects. In a study of 4 year old children, those who watched a fast-paced television cartoon performed significantly worse on the executive function tasks than children who watched educational programs or did drawings. Furthermore, researchers have found that a 3-year-old who watches two hours of TV per day is 20% more likely to have attention problems at age 7 than a child who watches no television. Other studies have shown that the content of the programs is important and the viewing of educational programs can have a positive outcome. Cognizant of this, the American Academy of Pediatrics strongly discourages television viewing for children ages two years old or younger, and encourages interactive play. For older children it recommends time-limited and parent-monitored viewing.

As a result of much time spent on indoor activities related to the latest electronic diversions, and to elements of our built environment, many children do not play outside; and, given our reliance on motor vehicles for transportation, children are not as active as they should be. As a result they do not benefit from real life experiences that help them grow and learn. Richard Louv, author of Last Child in the Woods, has called it Nature Deficit Disorder. This phenomenon should be viewed not as a direct cause of neurodevelopmental problems but rather as the prevention of optimal neurodevelopment.

Social and economic factors

There are two major environmental factors that adversely affect brain development and function in children who come from backgrounds of poverty.

1. They are more likely to be exposed to toxins, e.g. they may be as much as three times more likely to have lead toxicity than their more affluent counterparts. Environmental hazards, such as heavily polluting industries, hazardous waste sites with contaminated water and soil are often located in or near poor communities because these areas are undesirable and inexpensive and because the communities are politically disenfranchised. Furthermore, they are more likely to live in older housing, with poor indoor air quality and deteriorating lead based paint, adjacent to major roadways where hazardous substances are transported, lack of or limited green space, limited access to healthy food options, unsafe neighborhoods, and poor education in a substandard school building.
2. Growing up in circumstances of social and economic disadvantage can have an adverse effect on brain development and brain physiology. Children who come from family environments plagued by low income, unemployment, chronic housing mobility, and are subjected to abuse and neglect over a long period of time without respite, are likely to suffer from chronic stress. Stress is hormonally mediated and, if chronic, can result in permanent changes in brain anatomy and physiology, with functional consequences on how children deal with stress, their level of self-organization, and, importantly, their ability to pay attention and learn. This affects their educational achievement, eventual employability, ability to take care of a family, and their health status as adults. The phenomenon has come to be called Toxic Stress.

This intergenerational pattern contributes significantly to Environmental Health Disparities and can be viewed as a cycle. (See diagram). It challenges us, as responsible members of society, to improve the opportunities for children to reach their full potential by eliminating environmental hazards, reducing exposure to stress, improving education, raising public awareness and influencing public policy.