Fetal BPA exposure increases risk of prostate cancer later in life

Fetal exposure to a commonly used chemical found in products such as water bottles, soup can liners and paper receipts can increase the risk for prostate cancer later in life, according to a study from the University of Illinois at Chicago.

Bisphenol A, or BPA, is widely used to soften plastics. Steering clear of the chemical is nearly impossible, says Gail Prins, professor of physiology at UIC and lead author of the paper.

“Previous studies have shown that people who avoided all contact with plastics or other BPA-containing objects for up to a month or more still had BPA in their urine, which means they must have come into contact with BPA in the last 24 to 48 hours, since it clears the body rather quickly,” said Prins, who is director of the UIC andrology laboratory. “It’s very hard to avoid.”

Exposure of the fetus to BPA in utero is of particular concern, because the chemical, which mimics the hormone estrogen, has been linked to several kinds of cancer, including prostate cancer, in rodent models. The new findings show that human prostate tissue is also susceptible.

“Our research provides the first direct evidence that exposure to BPA during development, at the levels we see in our day-to-day lives, increases the risk for prostate cancer in human prostate tissue,” Prins said. “The findings of adverse effects of BPA in human tissue are highly relevant and should encourage agencies like the Food and Drug Administration to re-evaluate their policies in the near future.”

Prins investigated the effect of BPA on human cells by implanting human prostate stem cells taken from deceased young-adult men into mice. Prostate stem cells are very long-lived. They arise during early fetal development and produce and maintain a man’s prostate tissue throughout his life.

To mimic exposure to BPA during embryonic development, for two weeks following implantation the mice were fed BPA — in amounts in line with those seen in pregnant American women — as the cells produced humanized prostate tissue.

“The amount of BPA we fed the mice was equivalent to levels ingested by the average person,” Prins said. “We didn’t feed them exorbitantly high doses.”

After the tissue was allowed to mature for one month, the mice were given estrogen to mimic the naturally rising estrogen levels seen in aging men. This rise in estrogen later in life is one of the known drivers of prostate cancer.

Tissue was collected after two to four months and analyzed for prostate disease. Prins found that a third of tissue samples taken from mice fed BPA had either pre-cancerous lesions or prostate cancer, compared to only 12 percent in a control group of mice fed oil. If the prostate stem cells were exposed to BPA before implantation and again as they produced prostate tissue in the mice, 45 percent of the tissue samples had pre-cancerous lesions or cancer.

“We believe that BPA actually reprograms the stem cells to be more sensitive to estrogen throughout life, leading to a life-long increased susceptibility to diseases including cancer,” Prins said.

The study was published in the journal Endocrinology.

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Industrial air pollution linked to child heart defects

Children’s congenital heart defects may be associated with their mothers’ exposure to specific mixtures of environmental toxins during pregnancy, according to research presented at the American Heart Association’s Scientific Sessions 2013.

Congenital heart defects occur when the heart or blood vessels near the heart don’t develop normally before birth. Defects may be caused by chromosomal abnormalities, but the cause is unknown in most cases.

Researchers examined patterns of congenital heart defects incidence and presence of environmental toxicants in Alberta, Canada. The ongoing research seeks to determine if pregnant women’s proximity to organic compounds and metals emitted in the air impacts the risk of heart defects in their children.

“Although still in the early stage, this research suggests some chemical emissions — particularly, industrial air emissions — may be linked to heart abnormalities that develop while the heart is forming in the womb,” said lead researcher Deliwe P. Ngwezi, M.D., a Ph.D., student and research fellow in pediatric cardiology at the University of Alberta in Canada.

The study is based on congenital heart defects diagnosed in 2004-11 and chemical emissions recorded by a Canadian agency tracking pollutants.

Researchers looked at three chemical categories, but only one group showed a strong correlation with rates of congenital heart defects. According to Ngwezi, the group of chemicals consists of a mixture of organic compounds and metals namely: benzene, butadiene, carbon disulphide, chloroform, ethylene oxide, hexachlorobenzene, tetrachloroethane, methanol, sulphur dioxide, toluene, lead, mercury and cadmium.

Congenital heart defect rates have gradually decreased in Canada since 2006, which is about the time the government tightened regulations to reduce industrial air emissions, Ngwezi said. The heart defect decreases were mainly associated with heart defects resulting in holes between the upper and lower heart chambers (septal defects) and malformations of the cardiac outflow tracts (conotruncal defects), according to Ngwezi.

“For now, consumers and healthcare providers should be educated about the potential toll of pollutants on the developing heart,” she said. “As we have observed in the preliminary results, when the emissions decrease, the rates of congenital heart defects also decrease.”

This study, she said, should draw attention to the increasing evidence about the impact of environmental pollution on birth defects. Limitations of the study include that researchers’ observations were made at a group level, not according to individual risk and the self-reported industry data which is monitored and collected annually by government, according to Ngwezi.

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Phthalate exposure linked to preterm birth

The odds of preterm birth for women exposed to a commonly used class of chemicals known as phthalates are increased significantly, according to a new study from the University of Michigan School of Public Health and Brigham and Women's Hospital in Boston.

Depending on the individual phthalate, women with the highest levels of exposure during pregnancy had two-to-five times the odds of preterm birth, compared to women with the lowest exposure.

Before interventions can be implemented, however, more must be known about how phthalates interact with pregnancy, their potential association with women delivering early, and where exposures are coming from, the researchers caution.

"Preterm birth is a major public health challenge. Rates are significantly higher than they were 20 years ago and we don't know why. Other interventions have had limited effectiveness, and this helps shed light on a potential for environmental influences," said John Meeker, associate professor of environmental health sciences and associate dean for research at the U-M School of Public Health, who is the principal investigator of the study. "Next, we need to look at how pregnant women are exposed, and at what stage of pregnancy, to help inform exposure and risk prevention strategies."

Phthalates are used to make plastic materials more flexible and as solvents in personal care products such as perfumes, deodorants and lotions. They are found in food, adhesives, vinyl flooring, plastic shower curtains, some medications and more.

Meeker and colleagues studied 482 individuals selected from a larger population of pregnant women who delivered at the Brigham and Women's Hospital from 2006-08. For each woman, phthalate levels were measured in urine samples taken from up to three time points during pregnancy. The 130 mothers who delivered prior to 37 weeks showed significantly higher concentrations of four of nine phthalate metabolites that were measured in the study.

Dr. Thomas McElrath, a physician-scientist and key co-investigator on the study, developed and leads the original cohort study upon which this work is based in the Department of Obstetrics and Gynecology at Brigham and Women's Hospital.

"This is by no means the cause of premature birth, but it is a possible contributor—which is important because it is potentially modifiable," McElrath said. "This finding may be dramatic but women should not be alarmed. This is only the first step in a long research process that will be needed to clarify and confirm these results. It is simply too early to suggest making changes in prenatal care based on this study."

Kelly Ferguson, doctoral student at the U-M School of Public Health and first author of the paper, says the team's research provides the largest study of this relationship to date, and further improves on other studies by using multiple exposure measurements per subject.

"We have some ideas on how phthalates could cause preterm birth, although the exact mechanism is still unknown," she said. "One possibility we are considering is that phthalates are causing changes in oxidative stress or inflammation in the mother, and that these changes are leading to early labor."

The researchers say current studies remain inconclusive in assessing whether avoiding perfume, deodorant and other personal care products, and eating more fresh foods that undergo less processing and packaging, could lower women's phthalate exposure levels.

"Once we know more about pathways of exposure and mechanisms that cause this to happen, then it will be the time for interventions and policy action at the individual, clinical and federal levels," Meeker said. "These are things we are actively researching."

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Contaminated water breeds low-weight babies, sometimes born prematurely

Pregnant women living in areas with contaminated drinking water may be more likely to have babies that are premature or with low birth weights (considered less than 5.5 pounds), according to a study based at Princeton University's Woodrow Wilson School of Public and International Affairs.

Featured in the Canadian Journal of Economics, the study shows that the effects of contaminated water—which include numerous cognitive and developmental impairments—are particularly significant for babies born to less-educated mothers. These mothers also are less likely to uproot from areas with contaminated water, which, the authors note, suggests a need for serious improvement in terms of communicating with people living in such areas.

"Fetuses are vulnerable to all types of pollution, including water contamination caused by chemicals and bacteria," said Janet Currie, the Henry Putnam Professor of Economics and Public Affairs at the Woodrow Wilson School of Public and International Affairs and director of the Center for Health and Wellbeing. "This contamination can lead to a host of problems, including low-birth-weight babies who can have lifelong cognitive struggles. It's a particular problem for less-educated women who also presumably have less options in terms of housing."

While past studies have focused on the effects of air pollution on infant health, Currie's is one of the first to evaluate the effects of water pollution on infants. Together with researchers from Columbia University and the University of California, San Diego, Currie examined ten years of New Jersey birth records and data on drinking-water quality collected from 1997 to 2007. All birth records contained information regarding the date of birth, an infant's health at birth and maternal characteristics such as race, education and marital status. To determine whether mothers relocated due to water contamination, the researchers studied sets of siblings and whether mothers moved between births.

Using data from the New Jersey Department of Environmental Protection (DEP), Currie and her team looked at violation records across 488 water districts in New Jersey and found that more than a quarter of districts had water contamination violations affecting more than 30,000 people. These violations included both chemical and bacterial contamination caused by such contaminants as dichloroethane—a solvent often used for plastics or as degreasers— as well as radon and coliform.

The researchers matched the birth records to the water systems that serve the infants' residences. Because weather can dictate the amount of water a person consumes, they also incorporated daily temperatures into their dataset.

"We found that infants exposed to contamination in utero tend to have mothers who are younger, less educated and less likely to be married than other mothers. They are also more likely to be African-American or Hispanic," Currie said. "The results also suggest that mothers who are less educated are less likely than other mothers to move in response to contamination, while older mothers are more likely to drink bottled water or move."

Currie notes that when a water district is affected, the DEP is required to send a notice to all residences. However, for renters, there may be routing difficulties.

"If someone puts something in your mailbox, do you even see it? Does your landlord pick it up?" said Currie. "Notices are being sent that people don't receive. There's an undercurrent here that the way information is sent isn't adequate. We need to get this information to people directly."

Currie suggests that health-care workers include literature about water contamination risks and hazards in clinics and exam rooms to reach more pregnant women.

"If it's going to be harmful for some groups, we need to at least let those groups know about them, so they can avoid it," said Currie.

In the future, Currie plans to continue studying environmental impacts on child health while also pursuing the relationship between home foreclosures and health.

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Smoking during pregnancy may increase risk of bipolar disorder in offspring

A study published in the American Journal of Psychiatry suggests an association between smoking during pregnancy and increased risk for developing bipolar disorder (BD) in adult children.

The researchers evaluated offspring from a large group of pregnant women who participated in the Child Health and Development Study (CHDS) from 1959-1966. The study was based on 79 cases and 654 comparison subjects. Maternal smoking during pregnancy was associated with a twofold increased risk of BD in their offspring.

Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and attentional difficulties. This is the first study to suggest an association between prenatal tobacco exposure and BD, a serious psychiatric illness. The condition is marked by significant shifts in mood that alternate between periods of depression and mania. Symptoms typically become noticeable in the late teens or early adulthood.

"These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time," said Alan Brown, MD, MPH, senior author and Professor of Clinical Psychiatry and Epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health.

A previous study by Dr. Brown and colleagues found that flu virus in pregnant mothers was associated with a fourfold increased risk that their child would develop BD.

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Flame Retardants in Blood Drop after State Ban

A class of flame retardants that has been linked to learning difficulties in children has rapidly declined in pregnant women’s blood since the chemicals were banned in California a decade ago, according to a study led by researchers at UC San Francisco.

Blood levels of polybrominated diphenyl ethers (PBDEs), tested in patients at the UCSF-affiliated San Francisco General Hospital and Trauma Center fell by two-thirds since they were last tested three years ago and found to be the highest levels reported among pregnant women anywhere in the world.

Researchers said the dramatic decline was most likely the result of the statewide ban, as well as a voluntary national phase out. But they said the levels fell more quickly than expected, given how persistently these chemicals remain in the environment once they have been introduced.

“We were pleasantly surprised by the extent of the decline,” said Ami R. Zota, ScD, an assistant professor of environmental and occupational health at the George Washington University School of Public Health and Health Services, and the study’s lead author. Zota conducted the research while she was a postdoctoral fellow at UCSF’s Program on Reproductive Health. “Regulations can have an impact on people’s everyday lives.”

PBDEs were used in foam furniture starting in the 1970s to meet the state’s fire safety regulations, which are now being reviewed. Experiments in animals and also in human cells have shown that PBDEs damage the brain in utero. Researchers have found a strong relationship between an expectant mother’s exposure to the chemicals – even at low levels – and subsequent learning difficulties in her child, including worsened concentration and attention and lower IQ. The chemicals also can disrupt thyroid hormones in adulthood and during development. While much of the data is correlational, the researchers said there is enough evidence to raise serious concern that the chemicals are harmful to people.

PBDEs get into the body in different ways. They easily wear off foam and degrade into household dust, which gets ingested. The chemicals also find their way in through diets rich in fish, meat and dairy products, as PBDEs in the environment are persistent and can accumulate up the food chain. Nursing mothers also pass them to their babies through breast milk.

Previous research has shown that the PBDEs present in California house dust have fallen since the ban. But this is the first time that researchers have shown a decline in PBDEs in people since the chemicals were phased out.

San Francisco General Hospital, the city’s public hospital, serves vulnerable populations, who may be at higher risk for exposure to PBDEs because they are more likely to own older, cheaper furniture and live in poor housing conditions. The researchers compared a group of 25 women who came to the hospital from 2008 to 2009 to 36 women who came between 2011 and 2012. The first group had the highest reported levels of PBDEs of any group of pregnant women tested worldwide. But in just three years, overall levels fell by two-thirds.

Every woman tested from 2008-2009 had all five of the PBDEs measured by the researchers in her blood. But by 2011-2012, only one of the PBDEs was present in every woman tested. The researchers did not test the same women at both time points, but they did find that overall levels of all five PBDE’s were significantly lower in the second group.

Although PBDEs have been banned, furniture makers have substituted other chemicals, which may also be dangerous, as a way of meeting state fire safety standards. Chlorinated Tris, for example, is a suspected carcinogen listed on Proposition 65. Others, such as Firemaster 550, have not adequately been tested.

The findings were published online on Sept. 25 in Environmental Science & Technology.
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Fetal changes associated with mother’s chemical exposure

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A study led by researchers at the Johns Hopkins Bloomberg School of Public Health has for the first time found that a mother’s higher exposure to some common environmental contaminants was associated with more frequent and vigorous fetal motor activity. Some chemicals were also associated with fewer changes in fetal heart rate, which normally parallel fetal movements.

The study of 50 pregnant women found detectable levels of organochlorines in all of the women participating in the study—including DDT, PCBs and other pesticides that have been banned from use for more than 30 years. The study is available online in advance of publication in the Journal of Exposure Science and Environmental Epidemiology.

“Both fetal motor activity and heart rate reveal how the fetus is maturing and give us a way to evaluate how exposures may be affecting the developing nervous system. Most studies of environmental contaminants and child development wait until children are much older to evaluate effects of things the mother may have been exposed to during pregnancy; here we have observed effects in utero,” said Janet A. DiPietro, PhD, lead author of the study and Associate Dean for Research at the Bloomberg School of Public Health.

For the study, DiPietro and her colleagues followed a sample of 50 high- and low- income pregnant women living in and around Baltimore, Md. At 36 weeks of pregnancy, blood samples were collected from the mothers and measurements were taken of fetal heart rate and motor activity. The blood samples were tested for levels of 11 pesticides and 36 polychlorinated biphenyl (PCB) compounds.

According to the findings, all participants had detectable concentrations of at least one-quarter of the analyzed chemicals, despite the fact that they have been banned for more than three decades. Fetal heart rate effects were not consistently observed across all of the compounds analyzed; when effects were seen, higher chemical exposures were associated with reductions in fetal heart rate accelerations, an indicator of fetal wellbeing. However, associations with fetal motor activity measures were more consistent and robust: higher concentrations of 7 of 10 organochlorine compounds were positively associated with one of more measures of more frequent and more vigorous fetal motor activity. These chemicals included hexachlorobenzene, DDT, and several PCB congeners. Women of higher socioeconomic status in the study had a greater concentration of chemicals compared to the women of lower socioeconomic status

“There is tremendous interest in how the prenatal period sets the stage for later child development. These results show that the developing fetus is susceptible to environmental exposures and that we can detect this by measuring fetal neurobehavior. This is yet more evidence for the need to protect the vulnerable developing brain from effects of environmental contaminants both before and after birth,” said DiPietro.

“Fetal heart rate and motor activity associations with maternal organochlorine levels: results of an exploratory study” was written by Janet A. DiPietro, Meghan F. Davis, Kathleen A. Costigan, and Dana Boyd Barr.

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Chemical Exposure: Study Shows BPA Exposure in Fetal Livers

New research from the University of Michigan School of Public Health found BPA, or bisphenol A, in fetal liver tissue, demonstrating that there is considerable exposure to the chemical during pregnancy.

Researchers also found a proportionately higher concentration of free BPA—as opposed to the conjugated forms modified by the body for elimination—further showing that in fetuses the ability to eliminate the chemical from the body is not the same as in adults.

"The general message from our research is that people have to be cognizant of the fact that the adult body may be able to deal with a particular exposure but a developing fetus may not," said Muna Nahar, doctoral student in the School of Public Health's Department of Environmental Health Sciences and first author on the paper.

Previous animal studies have associated BPA with breast and prostate cancer, and reproductive and behavioral abnormalities. Some research on effects to human health has tied BPA to cardiovascular disease, miscarriage, decreased semen quality and childhood behavioral issues. The chemical also may impact metabolism, diabetes and obesity, although more studies are required to determine its effects.

"The finding of free BPA in fetuses is significant," said Dana Dolinoy, the John G. Searle Assistant Professor of Environmental Health Sciences and senior/corresponding author of the study.

After measuring a three-times-higher concentration of free BPA than the conjugated forms in the fetal livers, the researchers then examined the enzymes responsible for metabolizing the chemical and compared them with those at work in adult male and female livers.

"Our research shows that the argument that it's so rapidly metabolized is not true in fetuses," Dolinoy said.

The study appears online in the Journal of Biochemical and Molecular Toxicology

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Study: Chemical exposure and pollutants may impact ability to conceive

Researchers at the National Institutes of Health are reporting that couples with high levels of PCBs and similar environmental pollutants take longer to conceive a child.

PCBs (polychlorinated biphenyls) are chemicals that have been used as coolants and lubricants in electrical equipment. They are part of a category of chemicals known as persistent organochlorine pollutants and include industrial chemicals and chemical byproducts as well as pesticides.

The compounds are also resistant to decay, and may persist in the environment for decades. Some, known as persistent lipophilic organochlorine pollutants, accumulate in fatty tissues. Another type, called perfluorochemicals, are used in clothing, furniture, adhesives, food packaging, heat-resistant non-stick cooking surfaces, and the insulation of electrical wire.

Exposure to these chemical pollutants is known to have a number of effects on human health, but their effects on human fertility-- and the likelihood of couples achieving pregnancy-- have not been extensively studied.

To conduct the study, the researchers enrolled 501 couples from four counties in Michigan, and 12 counties in Texas, from 2005 to 2009. Couples provided blood samples for the analysis of organochlorines (PCBs) and perfluorochemicals (PFCs). Women kept journals to record their monthly menstrual cycles and the results of home pregnancy tests. The couples were followed until pregnancy or for up to one year of trying.

For each standardized increase in chemical concentration the researchers measured, the odds of pregnancy declined by 18 to 21 percent for females exposed to PCB congeners 118, 167, 209, and the perfluorchemical, perfluorooctane sulfonamide. Perfluorooctane sulfonamide is one of a broad class of compounds known as perfluoroalkyls, which have been used in fire fighting foams.

With increasing exposure, the odds for pregnancy declined by 17 to 29 percent for couples in which males were exposed to PCB congeners 138, 156, 157, 167, 170, 172, and 209 and to DDE, produced when the pesticide DDT degrades in the environment. DDT is banned for use in the United States, but is still used in some countries.

The investigators noted that they cannot rule out that some of the delays they observed may have been due to exposure to multiple chemicals. They added that these associations would need to be confirmed by other researchers.

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