Preterm birth, when a baby is born before 37 weeks, is a pressing public health problem because babies born early have greater risks of mortality and health complications and later disease in child and adulthood. In 2017 alone, California had more than 400,000 preterm births an increased rate of 8.6%compared to the previous year.

Though we know that genetic factors, exposures to chemicals including air pollutants, and social factors such as and race and poverty can all raise preterm birth risk, there’s a lot we still don’t know about the causes of preterm birth—especially when it comes to environmental and social stressors. We do know that pregnant women in California are exposed to multiple environmental pollutants from air, food, water and consumer products. We also know that pregnant women can experience social stress due to factors such poverty, food insecurity and discrimination.

So in our new study, we set out to investigate the relationship between preterm birth and cumulative burdens of multiple environmental exposure and social stressors. We used a novel integrative big data approach to link two large datasets—1.8 million California birth records with environmental exposure information from CalEnviroScreen, a database that contains thousands of data points on environmental pollution and social factors for every census tract in California. By leveraging large datasets, we were able to reveal new, and surprising, patterns.

We found that arsenic pollution in drinking water is significantly associated with an increase in preterm birth of 1%, by comparing preterm birth in populations with different levels of arsenic contamination in drinking water. This may seem very small, but because there are so many pregnant women exposed to arsenic in their drinking water, it can translate into sizeable population impacts.. In our study of almost 2 million births, most of the pregnant women are living in area with arsenic contamination in the drinking water. For example, if the preterm birth rate for population without arsenic exposure is 7.0%, our study suggests that the same population with arsenic exposure in drinking water will have 1% increase in preterm birth rate (7.07%), which is around 1400 additional preterm births across a population of 2 million because of arsenic in drinking water. This shows how a small increase in risk spread across many people can translate to big impacts.

An additional finding is that there are many people living in area where arsenic concentration in drinking water is higher than regulatory standard. For example, the U.S. EPA’s maximum contaminant levels (MCL) is 10 parts per billion (ppb), which suggests that many people living in those areas are at higher risks of arsenic exposure (shown in figure below).

U.S. EPA adopted this standard for arsenic in drinking water in 2001 with consideration for the various health effects associated with arsenic exposure, including “cancerous effects (skin, bladder, lung, kidney, nasal passages, liver and prostate) and non-cancerous effects: cardiovascular, pulmonary, immunological, neurological and endocrine (e.g., diabetes) effects”. While pregnant women exposed to arsenic in drinking water may have increased risk of preterm birth, the rest of the population may face different risks related to these other diseases.

In addition, we found that both environmental chemical exposures and social stressors such as PM_2.5, nitrate in drinking water and neighborhood unemployment rate collectively are associated with increased risk of preterm birth. This study adds to the evidence that cumulative impacts of multiple environmental and social factors are associated with adverse health outcomes. Note that there are some limitations and assumptions made in this study. For example, given the design of the environmental database used, we assume constant pollution during the entire pregnancy, and therefore didn’t account for temporal variability.

The power of our study shows how data collected in California can be used to identify potential risk factors that deserve more attention in research, monitoring and efforts that prevent exposures to harmful pollutant levels in order to better improve prenatal health.

Other co-authors on this work include: Tracey J. Woodruff (UCSF), Rebecca J. Baer (UCSD), Komal Bangia (OEHHA), Laura M. August (OEHHA), Laura L. Jellife-Palowski (UCSF), Amy M. Padula (UCSF, senior author), Marina Sirota (UCSF, senior author).

Did you know that there are more than 80,000 chemicals registered for commercial use in the US, with an estimated 2,000 new ones being introduced each year?  More than 30,000 pounds of chemicals are manufactured and imported for every American, nearly 15 times of the amount of food that one would eat annually.

Believe it or not, for most of these chemicals, we have no idea whether they can enter the human body—but studies that measure chemicals in people (called biomonitoring), which currently can measure about 350 chemicals, have found numerous chemical exposures in different populations. For example, a study found at least 43 different chemicals of a representative sample of U.S. pregnant women. And sadly, our new study suggests this is just the tip of the iceberg.

We used an innovative approach to identify novel chemicals never measured before in pregnant women’s blood, suggesting that moms-to-be are exposed to more chemicals than we previously knew. This raises concern for both women and children’s health, because chemicals can cross the placenta, and the developing fetus can be more sensitive to the adverse effects of these chemicals. Scientific evidence finds that in utero exposures to environmental chemicals can have health implications for the individual over the lifespan.

To uncover what hidden chemicals might be in pregnant women, we used high-resolution mass spectrometry technology to screen for a broad array of chemicals from maternal blood samples collected from 75 pregnant women. Still, screening for chemicals in a person is like finding needles in a haystack as blood contains thousands of chemicals and break-down products derived from not only environmental chemicals but also food, drugs and supplements etc. Thus, we used a novel approach called “suspect screening”, where we compiled a chemical database including ~700 chemicals found in pesticides, consumer products and industrial uses. This database served as a “road map” to guide our search in the novel environmental compounds, i.e., we are looking for the known unknowns (“suspect” compounds that have the same molecular weight as the chemical in our database). Then, we selected suspect chemicals for identity confirmation by comparing their mass profile to the corresponding reference standards (see figure below).

We found an average of 56 suspect chemicals in each sample and confirmed the presence of six novel chemicals (see table below). Two of these six chemicals – 2,4-Di-tert-butylphenol and pyrocatechol – have a production volumes of 10 million to 50 million pounds/year in the U.S. We have limited information on the uses and health hazards for many of these chemicals. In addition, our suspect screening method was limited to the chemicals covered in our database, which represents a small fraction of the full universe of chemicals in current use.  In reality, pregnant women are likely exposed to many more chemicals than we could screen for.

Chemicals can get into a women’s body when they use products, breathe in contaminated air, drink contaminated water, or eat contaminated food. As a next step, we are developing a method to measure the level of these previously unidentified chemicals in pregnant women and evaluate their impact on health.

A lot of us assume that the government carefully reviews the safety of chemicals before they enter the market, but unfortunately this is not the case. We actually have little information on most of the chemicals in commerce. It’s a daunting task to figure out which ones of the thousands of chemicals may pose health hazards to humans, especially to vulnerable populations like pregnant women and children. Our study offers a new approach to more efficiently screen for these chemicals and help prioritize certain ones for further research including toxicity testing and health effect studies.

While we are finding answers to important questions about the unknowns, we already have enough scientific evidence to take action now to reduce our body’s chemical burden. For practical tips on how to prevent chemical exposures at home, at work, and in your community, check out PRHE’s All That Matters brochure series in both English and Spanish.

You can also view this blog post in Chinese.

My co-authors on this study were: Roy Gerona, Jackie Schwartz, Thomas Lin, Marina Sirota, Rachel Morello-Frosch (UC Berkeley), and Tracey Woodruff (senior author). I would also like to thank the clinicians, clinical research coordinators, and all Chemicals in Our Bodies 2 (CiOB2) study participants for their contribution to the study.

About 1 in 33 babies are born with a birth defect. Spina bifida, a neural tube defect, which is one of the most common birth defects, affects about 4 in 10,000 – 1,500 babies are born with spina bifida each year in the U.S. Spina bifida occurs when the neural tube does not close completely during development and can have a significant effect on the physical and neurologic well-being of a child. Because of this, it is a leading cause of disability in children.

To help women have healthy pregnancies and babies, I investigate what causes birth defects like spina bifida. Evidence indicates multiple factors can increase the risk of spina bifida including the environment, genetics and nutrition. Spina bifida tends to run in families – after having one child with the condition or if one of the parents has the condition, there is a 4% chance that the next child will also be affected, suggesting that genes play a role. Studies also find that cigarette smoking, obesity and folic acid deficiency may make a woman more likely to have a baby with spina bifida, revealing the environment is also important. I am investigating how environmental exposures such as air pollution, in combination with additional factors like genes, may make a woman more likely to have a baby with a birth defect.

Since cigarette smoke and outdoor air pollution have similar components, it is possible that exposure to air pollution affects pregnant women the same way as cigarettes. Women are particularly vulnerable to the effects of air pollution when they are pregnant because of the changes that occur to carry and develop the fetus.

Indeed, my previous research found a link between air pollution and spina bifida– women exposed to high levels of outdoor air pollution (the chemicals carbon monoxide and nitrogen dioxide) were at higher risk of having a baby with spina bifida. Next, I wondered how mom’s genetic makeup might affect this risk. My recent paper was one of the first to investigate this question—how the combination of a mother’s genetic differences and air pollution exposure during early pregnancy may contribute to her risk of having a baby with spina bifida. We found that genetic differences could increase the risk– women exposed to high levels of air pollution (especially particulate matter) during early pregnancy and who had certain genetic differences had a higher likelihood of having a baby with spina bifida. Some of the genetic differences involved how the body reacts to environmental chemicals—suggesting that some people are more susceptible to the toxic effects of air pollutants because their body processes chemicals differently. My research has also found that chemicals are not the only stressors that can increase risks. My previous study found that women who were exposed to high levels of air pollution and lived in neighborhoods with more poverty (a socio-economic stressor) were more likely to have a baby with spina bifida.

Although we are at the early stages of investigating gene-environment combinations and socioeconomic factors, it is clear that the causes of birth defects may involve multiple factors. It is also apparent that air pollution and other environmental stressors contribute to risks, and that certain people may be more susceptible to these exposures. I plan to expand our research on gene-environment combinations and focus on additional environmental exposures including drinking water contaminants and specific air pollutants that are produced from traffic and fires. My research shows that we need to consider multiple factors, including genetics, that can put women and their babies more at risk from exposure to air pollution when we develop interventions and policies to reduce risks to debilitating birth defects. Policies need to incorporate the most current science on susceptibility to limit harmful environmental exposures and protect women and children’s health.

Amy Padula, PhD, is an Assistant Professor with the Program for Reproductive Health and the Environment in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California, San Francisco. Her doctorate is in Epidemiology from the University of California Berkeley and her postdoctoral training was at Stanford University.  Her research has been on the effects of ambient air pollution during pregnancy on adverse birth outcomes including preterm birth, low birth weight and birth defects. The projects have expanded to evaluate social factors, comorbidities during pregnancy and gene-environment interactions. Dr. Padula has an K99/R00 Transition to Independence Award from the National Institute of Environmental Health Science and las year was named one of the 20 Pioneers under 40 in Environmental Public Health by the Collaborative on Health and the Environment.

Dr. Padula’s co-authors on the papers referenced in the post above include: Gary Shaw, Wei Yang, Suzan Carmichael, Fred Lurmann, Ira Tager, Katharine Hammond and Kathleen Schulz.

Whether at the Oscars or the March for Science, women are increasingly standing up with each other and questioning the status quo in everything from entertainment to politics, including in my field of environmental health.

Protecting women during pregnancy from pollution might seem like an obvious public health objective, yet in the 40-plus year history of the Clean Air Act – under Democratic and Republican administrations alike – the US Environmental Protection Agency (EPA) has not given any special protection to pregnant women although it has legal authority, and arguably the duty, to do so.

Air pollution is associated with heart disease which can appear in women first during pregnancy, but women — and pregnant women in particular — are an under-studied group with respect to cardiovascular disease.  With air pollution, like particulate matter and ozone, we often worry about protecting children, but what about protecting mom?

In a paper published in World Medical and Health Policy in March 2018, my co-authors and I examined to what extent  Clean Air Act national ambient air quality standards consider pregnant women. A key finding of our paper is that pregnant women must be considered an at-risk population and given protection when EPA is making a decision about air pollution standards that include margin of safety which is mandated by the Clean Air Act. Our recommendation is consistent with statements from medical societies including the American College of Obstetrics and Gynecology, the American Heart Association, and the American Thoracic Society.

By law, the EPA Administrator considers three factors in setting standards: the nature and severity of the effects; the uncertainties in the data; and the size of the at-risk populations. How does EPA identify who is at risk? Currently, EPA starts with a health outcome and then backs out the group experiencing the effect. But this is antithetical to the preventative goals of the Clean Air Act and isn’t practical for an especially vulnerable group like pregnant women for whom ethical considerations would preclude some of the types of studies EPA’s procedures require. It’s a Catch-22; pregnant women would have to experience harm from air pollution before EPA would prevent the harm. To move beyond this flawed approach, we argue for the routine inclusion of pregnant women as an at-risk population.

First, the science supports the inclusion of pregnant women as an at-risk population under the Clean Air Act.  During pregnancy, women’s breathing volume increases by 40% to accommodate the demands of pregnancy and oxygen transfer across the placenta. Thus, pregnant women breathe in more pollutants than other adults. These natural compensatory changes that occur to the cardiopulmonary system during pregnancy are essential to maintaining the pregnancy, but these same adaptations may also render pregnant women more susceptible to additional health challenges, like air pollution exposure, which increases risk of adverse cardiovascular effects, contributing to poor health outcomes during pregnancy and beyond. In addition, pregnant women experience sensitive maternal exposure periods (e.g., during conception, placenta implantation, artery remodeling, and labor). Furthermore, air pollution is also associated with health problems only found among pregnant women (e.g., preeclampsia, gestational hypertension, and gestational diabetes). In setting air pollution standards, a risk assessment that specifically examines the effect on pregnant women is warranted.

Second, protection of pregnant women under the Clean Air Act would protect communities with the worst problems.  Nationally, disparities have been documented regarding exposure to air pollution among pregnant women by race/ethnicity, education, and income.  Women with preexisting conditions, women experiencing poverty, and groups that suffer systematic discrimination are more susceptible to cardiac effects of air pollutants during pregnancy.

In our study, we rigorously reviewed 11 studies of more than 1.3 million pregnant women in the United States to characterize the relationship between air pollution and high blood pressure – an indicator of cardiovascular problems – and an additional social stressor, such as lack of education.  We concluded that adequate evidence associates exposure to particulate matter with an adverse effect of hypertensive disorders among pregnant women.

From a policy perspective, the legislative history of the Clean Air Act and US EPA’s regulatory practice endeavor to protect sensitive groups, leading to fuller risk reduction across the population, while acknowledging the standards are not intended to be risk-free. We have previously pointed out deficits in EPA’s process, which could begin by identifying vulnerable groups.

Relying solely on scientific air pollution studies to identify vulnerable populations is logically flawed.  Essentially, these groups must first experience and demonstrate harm before being afforded protection under the law. These procedures conflict with the statutory language in the Clean Air Act’s goal of preventing likely harms from air pollution exposure. Furthermore, some groups, like pregnant women, may be especially difficult to study and thus are under-represented in the literature.

EPA’s risk assessment techniques should be improved to consider the impact of air pollution exposure on pregnant women’s health. The existing Clean Air Act standards set without these considerations are inadequate. EPA is misidentifying and thus underestimating the size of the at-risk population. EPA has a duty to protect at-risk populations with an adequate margin of safety. It is finally time that EPA fully assesses the risk to pregnant women and act to protect them.

Americans love going out to eat. In fact, two-thirds of the U.S. population dine out daily, according to our new study. While many of us know that dining out establishments typically serve larger meals that contain more butter, salt, and oil than foods we might prepare at home, how many of us know that chemicals with the potential to harm reproductive health and child development (called phthalates, or “thal-ates”) are also on the menu – even in our school cafeterias?

Our study found that people who dine out at restaurants, cafeterias, and fast food outlets have higher levels of multiple endocrine disrupting phthalates in their bodies. On average, nearly 35% higher than people who eat only at home.

This is especially of concern for pregnant women, young kids and teenagers, who are more sensitive to endocrine disrupting chemicals, which can interfere with hormone action during various stages of development. While phthalates are associated with many health impacts across a lifetime, including infertility, preterm birth, neurodevelopmental problems, obesity, diabetes, and cancer, the National Academy of Sciences (NAS) recently identified certain phthalates as presumed human reproductive hazards, and previously acknowledged their ability to collectively increase risk of genital malformations and other reproductive tract abnormalities in baby boys.

To reflect this reality in our new study, we assessed multiple phthalates in combination by accounting for some being more toxic than others, which is reflective of modern-day exposures and associated health risks.

We found that children 6-11 years old had the highest overall cumulative phthalate levels. Teenagers who consumed the highest percent of their total calories from dining out at restaurants, cafeterias, or fast food outlets had up to 55% higher phthalate levels than teens who strictly ate food from home (which was most likely purchased from the grocery store).

Phthalates are used widely in everyday consumer and personal care products, ranging from perfume to vinyl flooring, and some are restricted in children’s toys. However, most of our phthalate body burden comes from food. Phthalates are not intentional food ingredients but instead contaminate food products by migrating from various food contact materials along the food production supply chain (e.g. from conveyer belts, industrial tubing, food handling gloves, takeout food containers, and other food packaging materials).

While we knew that phthalate sources include fast food and many household food products, such as meat/poultry, dairy products, olive oil, and even spices, we didn’t know whether other dining out sources may contribute to phthalate levels or how dining out compares to eating at home. Our study found that full-service restaurants and cafeterias are probable sources of phthalates exposure and that dining out is associated with higher phthalate levels than consuming food from the grocery store.

Cafeteria sources of phthalates exposure are particularly relevant for children and adolescents, many of whom depend on the National School Lunch Program as a vital source of nutrition. The program provides 30 million school lunches daily across 95% of U.S. public and private schools.

Fast food, restaurant, and cafeteria food appear to contribute about equally to teen’s phthalate levels. The cafeteria food contribution was relatively low in children (15% compared to ≥ 45% in adolescents), despite more children consuming cafeteria meals than teenagers or adults. Different lunch options and food choices may partially explain this discrepancy; teenagers are typically served and often choose  lower quality foods than younger kids in the lunch room, which may increase phthalate levels.

Our study suggests that other sources besides dining out contribute to high phthalate levels in children, but our findings also show that school lunches may provide unique opportunities to reduce exposure in children and teens.

As a scientist, I know we need more research. As a mother of a two year old son, I want to act on what we do know. Phthalates have no place (or purpose) in our school cafeterias. Many schools are outsourcing meal preparations off-site, where fresh ingredients undergo processing into less healthy alternatives, which may increase school lunch contamination. Overly processed deep-fried meals can be modified to include healthier, fresh ingredients.

Ultimately, adequate, nutritious meals are the most important factors in healthy development. Other benefits include healthier diet preferences, reduced risk of obesity, and improved test scores. While our findings are not a reason for kids to avoid the school cafeteria – they are a reason for policy makers, food service providers, and others to take action and eliminate phthalates from school lunches.

Many phthalates are already banned from children’s toys; why are we serving them to kids at lunch?

My co-authors on this study were: Rachel Morello-Frosch at the University of California, Berkeley, School of Public Health, Tracey Woodruff, Director of the Program on Reproductive Health and the Environment (PRHE) at the University of California, San Francisco, and Ami Zota at George Washington University, Milken School of Public Health.

PRHE’s Toxic Matters brochure provides practical tips on how to reduce potentially harmful chemical exposures in everyday life.

Constant exposure to environmental pollutants can sicken our bodies, and social stressors such as poverty and psychological burden can further aggravate the health effects. For example, traffic-related air pollution has been linked to the onset of childhood asthma. However, if children exposed to air pollutants also experience violence, their risks of developing asthma can be doubled or tripled. Researchers and Scientists consider ‘cumulative risks’ (details here) as the elevated risks from the combined effects of multiple environmental and social stressors or agents, in this case air pollution and exposure to violence.

Understanding cumulative risk is important because we know very little about how synergistic interactions of multiple chemical exposures and social factors can increase risk of severe diseases, even though we are exposed to numerous chemicals via air, water, soil and consumer products on a daily basis. Until recently, a systematic-review of human and animal evidence confirmed the cumulative adverse effects of prenatal-exposure to chemicals and psychosocial stress on fetal growth. Individuals and different health organizations can take more effective actions to address such health issues once we can gain better knowledge relevant to cumulative risks.

The number of cumulative risk and impact studies increased tremendously over the past decade, but the relevant modeling methods have been underdeveloped to evaluate the joint exposures. Proper selection and use of statistical modeling techniques will generate accurate scientific results, which will contribute to sound environmental and public health policies.

To summarize modeling methods utilized to quantify the cumulative effects of multiple stressors in previous studies, we performed the first ever review on statistical models used to evaluate cumulative risks. I conducted a systematic search to identify original peer-reviewed research articles published between Jan 1, 2012- June 21, 2017 that evaluated both environmental and social stressors, and analyzed their health effects. We focused on human subject studies that provided quantitative method information. Eventually, we identified 31 eligible articles– the majority used simple regression models and focused on air pollutants and socio-economic status (SES) with various health outcomes, as shown in the table below.

We found that simple regression models, including multivariable and logistic regression models, are commonly used in cumulative risk studies, especially evaluating the combined effects of both chemical and non-chemical stressors. However, we wondered whether regression methods can properly cover all the combinations of different possible research settings such as research questions, study designs and data. Unfortunately, no. We found that regression methods, similar to other modeling techniques, has its own advantages and limitations (details here), and concluded that no single modeling technique can be applied universally to all cumulative risk studies.

With increasing knowledge in exposure science and the advent of more quantitative tools in the era of ‘big data’, we recommend that other data mining and machine learning techniques such as deep learning be considered in cumulative risk research, particularly when it comes to understanding the combined risks of multiple stressors. To provide public health protection for vulnerable populations such as pregnant women and children, risk assessment can take advantage of the established modeling methods while more approaches are being developed. Other authors on the study include Drs. Aolin Wang, Rachel Morello-Frosch (UC Berkeley), Juleen Lam, Marina Sirota, Amy Padula and Tracey Woodruff.