Autism is a complex and confounding developmental disability, and it’s on the rise.
The Centers for Disease Control and Prevention (CDC) recently announced that the prevalence of autism has risen to 1 in every 59 births in the United States.
In 2007, the CDC reported that 1 in 150 children had autism (based on 2002 data from 14 communities).
It’s not known how much of this increase in prevalence is due to better statistics thanks to an increase in autism awareness and access to services.
Regardless, while most research shows that autism is not caused by vaccines, there is still no single known cause.
Scientists are investigating possibilities such as unstable genes, problems during pregnancy or delivery, and environmental factors such as viral infections and exposure to chemicals.
Dr. Alan S. Brown, MPH, a psychiatrist and epidemiologist at Columbia University, has spent much of his career researching the risk factors for autism as well as schizophrenia and bipolar disorder.
His latest autism study could be among his most significant.
Brown and his international team looked at autism’s possible link to the insecticide DDT.
DDT (dichlorodiphenyltrichloroethane) was once widely used in the United States but was banned in 1972 by the Environmental Protection Agency (EPA) under then-President Richard Nixon because it was thought to be harmful to the environment, animals, and perhaps humans.
So why would Brown spend time studying a bug spray that was outlawed in the United States nearly five decades ago?
Because DDT persists in the food chain, he said. It can take as long as several decades for it to break down, resulting in its continued contact with humans, including expectant mothers.
Brown and his international team’s study of more than 1 million pregnancies in Finland showed a link between elevated levels of a metabolite of DDT in the blood of pregnant women and increased risk for autism in their children.
What the study revealed
The results of the study, led by Brown and other investigators at Columbia University’s Mailman School of Public Health and the Department of Psychiatry, were published today in the American Journal of Psychiatry.
Conducted in collaboration with investigators at the University of Turku and the National Institute of Health and Welfare in Finland, the study is the first to connect an insecticide with risk for autism using maternal biomarkers of exposure.
The study also examined mothers’ exposure to PCB’s (polychlorinated biphenyls), another class of environmental pollutants, and concluded there was no association between these substances and autism.
Brown said his team identified 778 cases of childhood autism among children born from 1987 to 2005 to women enrolled in the Finnish Maternity Cohort, representing 98 percent of pregnant women in Finland.
They matched these mother-child pairs with a control group of offspring of mothers as well as offspring without autism.
Maternal blood taken during early pregnancy was analyzed for DDE, a metabolite of DDT, and PCBs.
Investigators said they found the odds of autism with intellectual disability in offspring were increased by greater than twofold for the mother with DDE levels in the top quartile.
For the overall sample of autism cases, the odds were nearly one-third higher among offspring exposed to elevated maternal DDE levels.
The findings persisted after adjusting for several factors such as maternal age and psychiatric history. There was no association between maternal PCBs and autism, Brown said.
“This study provides us with a new risk factor that is prevalent in the environment and could account for minority of cases but not a small minority in terms of risk,” Brown told Healthline.
Unfortunately, Brown said, these chemicals are still present in the environment and are in our blood and tissues.
“In pregnant women, they are passed along to the developing fetus,” he said. “Along with genetic and other environmental factors, our findings suggest that prenatal exposure to the DDT toxin may be a trigger for autism.”
Brown’s team offered two reasons for their observation that maternal exposure to DDE was related to autism while maternal PCB exposure was not.
PCBs, or polychlorinated biphenyls, are industrial products or chemicals that were banned in the United States in 1979.
First, Brown’s team explained, maternal DDE is associated with low birthweight, a well-replicated risk factor for autism. In contrast, maternal PCB exposure has not been related to low birthweight.
Second, Brown’s team points to androgen receptor binding, a process key to neurodevelopment.
A study in rats found that DDE inhibits androgen receptor binding, an outcome also seen in a rat model of autism.
In contrast, PCBs increase androgen receptor transcription.
Other scientists comment
As with most research involving autism, this study brings some respectful disagreement among the experts.
Tracey Woodruff, PhD, MPH, who studies reproductive health and the environment at University of California, San Francisco, told the journal Nature today that the study “is really amazing.”
She said she is impressed by the number and quality of the samples in the Finnish database, and finds the association between DDT and autism striking.
“This just confirms that banning [DDT] was a good idea,” she said
But Thomas Frazier, PhD, chief science officer of Autism Speaks, was slightly less enthusiastic about the study.
He called it important but not groundbreaking.
“It suggests another potential environmental risk factor, DDT, but also did not replicate a previously identified risk factor, PCBs,” he told Healthline. “This highlights the need for large sample replication, particularly for autism risk factors.”
Frazier said the mechanism by which DDT may increase autism “is not known, and it may not be worth speculating until the finding is replicated. It is possible that DDT as a toxin influences gene expression in the developing brain.”
“The other important caveat in this study,” Frazier added, “is that association does not mean causation. While the authors did a good job of identifying similar cases and controls and adjusting for relevant factors, it is not possible to rule out other explanations.”
“Bottom line: This study is not groundbreaking, but it is well done and suggests the need for replication and a careful look at DDT in the future,” Frazier said.
Study leader’s response
Brown said he agrees with much of what Frazier said, but not all of it.
“I agree there is need for replication, but whether or not the study is groundbreaking, it is the first biomarker-based study, and that is worth noting,” Brown said.
Brown said the study argues for further studies that look at other mechanisms and other chemicals, including other insecticides.
“This, along with other evidence, will help us better understand the biology of autism,” Brown said. “We are learning every day, and we hope to do more studies.”
Brown said this study should not alarm women who are expecting.
He said the vast majority of women even with elevated levels of the DDT metabolite did not have offspring with autism.
This suggests that in order for autism to develop there would have to be a combination of other risk factors, including possible genetic mutations.
“It could be that you need some kind of genetic predisposition” combined with environmental exposure to get autism, he said.
Brown said this type of research could ultimately lead to treatments by identifying a subclass of people with certain genetic factors.
“The key is to identify a precise target, which would move this toward precision medicine,” said Brown.
He added there is also some evidence that in autism, a component of the immune system “might be dysregulated.”
Autism and the immune system
Another significant new autism study released just a few weeks ago concluded that developing autism is indeed determined by the expectant mother’s microbiome during pregnancy.
The findings of scientists at the University of Virginia (UVA) School of Medicine raise the possibility that some forms of autism could be prevented.
In a study published last month in The Journal of Immunology, scientists concluded that the mother’s microorganisms during pregnancy calibrate interleukin-17A (IL-17A) responses, which act as a key contributor to the development of autism-like disorder.
Interleukin-17A is an inflammatory molecule produced by the body’s immune system.
UVA researchers concluded that the effects of the microbiome on the development of autism could be prevented either by modifying the pregnant mother’s microbiome by improving the mother’s diet, providing the expectant mother with probiotic supplements, or performing a fecal transplant.
Another way would be to directly block IL-17A signaling, but that would be more problematic.
“We determined that the microbiome is a key contributor in determining susceptibility [to autism-like disorders], so it suggests that you could target either the maternal microbiome or this inflammatory molecule, IL-17A,” said lead researcher John Lukens, PhD, of UVA’s Department of Neuroscience.
“You could also use this [IL-17A] as a biomarker for early diagnosis,” Lukens said in a press statement.
He explained that the microbiome can shape the developing brain in multiple ways.
“The microbiome is really important to the calibration of how the offspring’s immune system is going to respond to an infection or injury or stress,” he said.
Lukens’ studies show that while an unhealthy microbiome in the mother can make her unborn offspring susceptible to neurodevelopmental disorders, the microbiome can be modified easily.
These approaches all seek to restore a healthy equilibrium among the different microorganisms that live in the gut, although researchers have yet to come up with specific dietary recommendations.
Blocking IL-17A also might offer a way to prevent autism, but Lukens said that path carries much more risk.
“If you think about pregnancy, the body is basically accepting foreign tissue, which is a baby,” he said. “As a result, maintenance of embryonic health demands a complex balance of immune regulation, so people tend to shy away from manipulating the immune system during pregnancy.”
IL-17A previously has been implicated in conditions such as rheumatoid arthritis, multiple sclerosis, and psoriasis. There are already drugs available that target it.
But Lukens noted that the molecule has an important purpose in stopping infections, especially fungal infections.
Blocking it, he said, “could make you susceptible to all kinds of infections. And doing so during pregnancy could have complex ripple effects on a child’s development that scientists would need to sort out.”
Insecticide/herbicide debate continues
The harm that insecticides and herbicides bring to humans has long been debated.
DDT, which was first synthesized in 1874, was initially used by the military in World War II to control malaria, typhus, body lice, and bubonic plague
Farmers used DDT on a variety of food crops in the United States and worldwide, and DDT was also used in buildings for pest control.
Worldwide, DDT is still used in small quantities in nations as an effective killer of mosquitos, including those that carry malaria.
DDT was so popular because it’s effective, relatively inexpensive to manufacture, and lasts a long time in the environment.
The World Health Organization in 2006 supported the pesticide as a way to control malaria.
Some environmental groups support the limited use of DDT to address the malaria crisis, but other groups say spraying DDT is harmful.
Some, such as the Cato Institute, want to bring DDT back in the United States.
But studies have shown a variety of human health effects linked to DDT and its metabolite, DDE, including miscarriages and low birth weight, nervous system and liver damage, breast and other cancers, developmental delay, and male infertility.
Monsanto’s embattled insecticides
Monsanto, the chemical company that has been embroiled in controversy over several of its chemically based products — from PCBs to bovine growth hormone to polystyrene to Agent Orange (dioxin) — was one of the first manufacturers of DDT.
Monsanto insisted for decades that DDT was safe. And now another herbicide from Monsanto is under fire for allegedly causing cancer.
This past week, a San Francisco jury ruled that Monsanto’s Roundup, the best-selling weed killer in the world, gave a former school groundskeeper non-Hodgkin’s lymphoma.
Dewayne Johnson, who is now reportedly dying of the cancer, was awarded $289 million in damages.
After the verdict, Monsanto issued a statement saying it stands by the particular studies that suggest Roundup does not cause cancer.
“We will appeal this decision and continue to vigorously defend this product, which has a 40-year history of safe use and continues to be a vital, effective and safe tool for farmers and others,” said Monsanto Vice President Scott Partridge.
Johnson’s victory could set a precedent for literally thousands of other cases claiming Monsanto’s popular herbicide causes non-Hodgkin’s lymphoma.
Johnson’s case was the first to go to trial because he was near death. In California, dying plaintiffs can request expedited trials
Monsanto had a similar defense for Agent Orange, the notorious herbicide that the Department of Veterans Affairs now acknowledges has harmed tens of thousands of American war veterans.
“The former Monsanto Company manufactured DDT from 1944 until 1957, when it ceased production for economic reasons,” the company writes on its website
“This halt occurred long before any environmental concerns were brought to the table, and to this day, we do not produce or distribute it. There is something to be said for the benefits of DDT, however. The World Health Organization has noted that DDT is an effective preventative measure for Malaria, a mosquito borne illness that takes millions of lives each year.”
Monsanto was recently purchased by Bayer, the global pharmaceutical company that received the Food and Drug Administration’s approval last year to market one of its newest and most promising drugs, Aliqopa, which treats non-Hodgkin’s lymphoma.