Air pollution contributes to 4.2 million deaths each year, according to the World Health Organization, with 91 percent of the world population living in areas where it is greater than the limits set by the organization’s guidelines. Studies have linked inhalation of pollutants to health conditions such as asthma, which is the leading chronic illness in children in the United States. Early research into the health effects of air pollution in the 1960s focused on adults, and by the 1970s, the link between breathing in particulate matter and respiratory disease became well established.
Around the same time, researchers began to consider the pervasiveness of polluted air as affecting not just those who breathe it, but also fetuses developing in utero. In 1973, the first study of the effects of air pollution on birth outcomes in the Los Angeles area found a link between in utero exposure to air pollution and low birth weight. Since then, researchers have uncovered myriad health effects in children tied to the quality of the air their mothers breathed while pregnant.
When she first moved to the Los Angeles area in 1989, says Beate Ritz, an epidemiologist at the University of California, Los Angeles School of Public Health, she found it hard to breathe because of the smog. By the early 1990s, she’d had two pregnancies and became concerned about how the air pollution may have affected her children, which led her to study pregnant women. In one of her first studies, she found that babies born in Los Angeles between 1994 and 1996 and whose mothers were exposed to high levels of pollutants during pregnancy had lower birth weights and were more likely to be born preterm than babies whose moms breathed cleaner air.
As in human epidemiological association studies, animal studies have also found that air pollution affects more than birth outcomes.
Although these findings were similar to the 1973 study, Ritz says in an email to The Scientist that she did not expect to be able to measure these effects so consistently, especially considering that the air quality in Los Angeles had improved since the 1970s. Los Angeles had gone from 0.68 ppm of ozone, the main compound found in smog, in 1955 to 0.14 ppm in 1996.
What she and other epidemiologists have found through numerous studies was prenatal exposure to air pollution from vehicles may affect children’s birth weights, gestation periods, and lung health after they are born and later in life. For example, children born to women who were exposed to higher levels of pollutants during pregnancy have lower levels of lung functioning, says developmental epidemiologist Rosalind Wright of the Icahn School of Medicine at Mount Sinai. In a study of seven-year-olds, those children, especially boys, who were exposed to nitrate from vehicle emissions during weeks six through 12 of gestation scored lower on lung capacity tests than kids who were exposed to lower levels. “And you can see that in children as young as five or six years of age, which is a problem because that really tracks for the rest of their lives,” she says. Other studies show that exposure to pollution while in the womb may also lead to sleep disorders and behavioral problems in kids.
Ritz says she’s convinced there’s a causal connection between air pollution exposure among pregnant moms and untoward health problems in kids, but the medical community hasn’t fully adopted that stance, she adds. The epidemiological evidence for the health effects of air pollution on fetuses has mounted over time, but as correlational studies they can’t show a causal relationship. “Doctors don’t believe that air pollution can cause adverse birth outcomes. . . . I think we have to show them that there is actually a biology behind it,” she says.
How air pollutants cause harm
Because correlational studies are not able to explain the mechanism of how developing fetuses might be affected by their mothers’ air pollution exposure, scientists have turned to animal models and experiments in the last few years.
The identity of the pollutant may not be as important as its size.
In one of the most recent such studies, geoscientist Renyi Zhang of Texas A&M University and his collaborators conducted experiments with rats, exposing pregnant females to ultrafine ammonium sulfate particles. Ammonium sulfate is a common air pollutant from industry and vehicle emissions, says Zhang. And the concentrations they used are comparable to what can be found in cities in Asia. In their study, they found that the offspring of pollutant-exposed rats had lower birth weights, were born sooner, and were more likely to be stillborn.
In studies of humans, researchers have difficulty teasing apart the effects of specific chemical compounds, although ammonium sulfate is often in the mix. But the identity of the pollutant may not be as important as its size. Zhang and his team specifically used ultrafine particles in their study because those may be the most dangerous to fetuses. “The small particles can actually get deeper into your body than the big particles,” says Zhang. Particulate matter that is smaller than 2.5 μm in diameter, and especially ultrafine particles that are 0.1 μm or smaller, can move through tissue. “They are quite well known to be able to actually go through cell membranes, and be found in lung lining cells,” says Ritz. The smallest particles can also cross the blood brain barrier or can eventually reach the placenta, she adds. The ability of very small particles to travel through the mother’s body and potentially into the fetus could be how air pollutants cause health and developmental problems in children, according to Ritz.
“One of the key mechanisms through which air pollution probably has its toxic effects is through enhanced oxidative stress,” says Wright. Pollutants such as ammonium sulfate, nitrogen dioxide, and ozone are known to react with cell membrane lipids and proteins. Experts tell The Scientist that they think those reactions can lead to inflammation, which may in turn contribute to preterm labor and birth. The exact mechanism for how this happens is not well studied, although researchers are working to understand how chronic inflammation influences signaling pathways that induce labor.
As in human epidemiological association studies, animal studies have also found that air pollution affects more than birth outcomes. For instance, in a study published in 2012, researchers exposed pregnant mice to higher than real-world concentrations of diesel exhaust, which resulted in the offspring gaining more weight than control animals when both were fed a high fat diet. Then a study in humans published in 2018 found that children exposed to pollution from living near roadways in their first year of life had a greater body mass index (BMI) by their tenth birthday than their peers.
Neuroscientist Jessica Bolton of the University of California, Irvine, who was the first author on the rodent study tells The Scientist the effects on the mice were not limited to metabolism. “So when we looked at the animals’ brains, there was evidence of neuroinflammation as well,” she says.
The pollutants might be causing inflammation in the brain of the fetus, which may affect neurodevelopment. To find out if inflammation is playing a role, Ritz’s group has begun analyzing urine and blood samples from pregnant women to check for biomarkers of inflammation.
These epidemiological and animal studies suggest the health effects of air pollution go beyond birth weight and preterm birth and may stay with the affected individuals their whole lives. Being able to predict who may be most at risk is one of the remaining goals for work in this field. “Pregnancy is a very important period in life when all organs [in the fetus] develop,” Ritz says, and exposure to pollutants can affect these organs as well as the whole fetus in a way that can have “life-long consequences.”
Chia-Yi Hou is a freelance science writer. Follow her on Twitter @chiayi_hou.