Phthalates heighten risk for childhood asthma

Researchers at the Columbia Center for Children's Environmental Health at the Mailman School of Public Health are the first to demonstrate an association between childhood asthma and prenatal exposure to two phthalates used in a diverse array of household products. Results appear online in the journal Environmental Health Perspectives.

Children born to mothers exposed during pregnancy to higher levels of the chemicals, butylbenzyl phthalate (BBzP) and di-n-butyl phthalate (DnBP) had a 72 percent and 78 percent increase in risk of developing asthma between age 5 and 11, respectively, compared with children of mothers with lower levels of exposure, the researchers found.

"Everyone from parents to policymakers is concerned by the steep rise in the number of children who develop asthma. Our goal is to try and uncover causes of this epidemic so we can better protect young children from this debilitating condition," says first author Robin Whyatt, DrPH, professor of Environmental Health Sciences and co-deputy director of the Columbia Center for Children's Environmental Health at the Mailman School.

"Our study presents evidence that these two phthalates are among a range of known risk factors for asthma," adds Dr. Whyatt. Other risk factors include tobacco smoke, air pollution, obesity, and a history of allergies.

Phthalates are used in everything from synthetic fragrances to plastic food containers, vinyl flooring, insect repellent, shower curtains, even steering wheels and dashboards ("new car smell" contains phthalates). Since 2009, several phthalates—including BBzP and DnBP—have been banned from children's toys and other childcare articles in the United States. However, no steps have been taken to protect the developing fetus by alerting pregnant women to potential exposures. In the U.S., phthalates are rarely listed as ingredients on products in which they are used.

"The fetus is extremely vulnerable during pregnancy. While it is incumbent on mothers to do everything they can to protect their child, they are virtually helpless when it comes to phthalates like BBzP and DnBP that are unavoidable. If we want to protect children, we have to protect pregnant women," says the study's senior author Rachel Miller, MD, professor of Medicine (in Pediatrics) and Environmental Health Sciences; and chief of Pediatric Allergy, Immunology, and Rheumatology at Columbia University Medical Center; and co-deputy director of the Columbia Center for Children's Environmental Health at Columbia's Mailman School of Public Health.

The researchers followed 300 pregnant women and their children enrolled in the Center's longitudinal cohort study in New York City. Levels of exposure to four suspect phthalates were measured through chemical metabolites in urine. Samples were collected from mothers during the third trimester and in children at ages 3, 5, and 7. Chemical analysis was done at the Centers for Disease Control and Prevention. The researchers compared asthma risk in the children between ages 5 and 11 year who were born to mothers with concentrations of the phthalates in the upper third versus the lower third.

Almost a third of the children (94) developed physician-diagnosed asthma. Another 60 children had a history of wheeze and other asthma-like symptoms without a diagnosis of asthma. In this group too, the researchers found a link between prenatal exposure to DnBP and the symptoms. Two phthalates studied—di-2-ethylhexyl phthalate (DEHP) and diethyl phthalate (DEP)—were not associated with a diagnosis of asthma or asthma-like symptoms.

All but one of the urinary samples from mothers and children contained metabolites for all four phthalates. Samples had a wide range of concentrations—from not detected to 550 ng/ml for the BBzP metabolites and from 1 to 1,110 ng/mL for DnBP metabolites. It is unclear what behaviors or products contributed to the greater exposures.

The current findings build on the team's 2012 studies on the same cohort of mothers and children and reporting that children exposed to DEP or BBzP had elevated risk of asthma-related airway inflammation and prenatal exposure to BBzP was associated with elevated risk of childhood eczema. In 2013, the researchers reported that early childhood exposure to bisphenol A (BPA) also was associated with risk for asthma. More recently, they found that the risk from BPA exposure during childhood increased substantially if the mothers also had higher exposure to BBzP during pregnancy, indicating these endocrine disruptors interact to increase childhood asthma risk (results were published in August in the Journal of Allergy and Clinical Immunology).

For now, it's not known how phthalates increase risk for asthma. Studies of prenatal exposure to BBzP hint that inflammation and oxidative stress may play a role.

The research was supported by grants from the National Institute of Environmental Health Sciences (NIEHS) (R01ES014393, R01ES13163) and NIEHS/U.S. Environmental Protection Agency (P01 ES09600/RD 83214101, P30ES009089). The researchers declare no competing financial interests.

Co-authors include Columbia Center for Children's Environmental Health director Frederica Perera, Matthew Perzanowski, Andrew Rundle, and Lori Hoepner—all of Columbia's Mailman School; Kathleen Donohue of Columbia University Medical Center; Allan Just of the Harvard School of Public Health; and Antonia Calafat of the Centers for Disease Control and Prevention.

Founded in 1922, Columbia University's Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master's and doctoral degree programs. The Mailman School is also home to numerous world-renowned research centers including ICAP (formerly the International Center for AIDS Care and Treatment Programs) and the Center for Infection and Immunity. For more information, please visit http://www.mailman.columbia.edu.