Mount Sinai finds prenatal exposure to certain chemicals affects childhood neurodevelopment


A new study led by Mount Sinai researchers in collaboration with scientists from Cornell University and the U.S. Centers for Disease Control and Prevention, has found higher prenatal exposure to phthalates—manmade chemicals that interfere with hormonal messaging—to be connected with disruptive and problem behaviors in children between the ages of 4 and 9 years. The study, which is the first to examine the effects of prenatal phthalate exposure on child neurobehavioral development, will be published January 28, on the Environmental Health Perspectives website.

“There is increasing evidence that phthalate exposure is harmful to children at all stages of development,” said Stephanie Engel, PhD, lead study author and Associate Professor of Preventive Medicine at Mount Sinai School of Medicine. “We found a striking pattern of associations between low molecular weight phthalates – which are commonly found in personal care products – and disruptive childhood behaviors, such as aggressiveness and other conduct issues, and problems with attention. These same behavioral problems are commonly found in children diagnosed with Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder, or Conduct Disorder.”

Phthalates are part of a group of chemicals known as endocrine disruptors, that interfere with the body’s endocrine, or hormone system. They are a family of compounds found in a wide range of consumer products such as nail polishes, to increase their durability and reduce chips, and in cosmetics, perfumes, lotions and shampoos, to carry fragrance. Other phthalates are used to increase the flexibility and durability of plastics such as PVC, or included as coatings on medications or nutritional supplements to make them timed-release.

“Recently, the government instituted regulations limiting certain phthalates in things like child care articles or toys that a young child might put in their mouth,” continued Dr. Engel. “But it’s their mother’s contact with phthalate-containing products that causes prenatal exposure. The phthalates that we found most strongly related to neurodevelopment were those commonly found in cosmetics, perfumes, lotions and shampoos. Current US regulations do not address these kinds of phthalates.”

For the study, phthalate metabolite levels were analyzed in prenatal urine samples of a multiethnic group of 404 women who were pregnant for the first time. The women were invited to participate in follow-up interviews when their children were between the ages of 4 and 9. The mothers were not informed of their phthalate metabolite levels and the researchers were unaware of their exposures when testing the children.

Follow-up visits were completed by 188 of the women and their children. At each follow-up visit, the mothers completed validated questionnaires designed to assess their behavior and executive functions. The researchers found that mothers with higher concentrations of low molecular weight phthalates consistently reported poorer behavioral profiles in their children. The strongest trends were in the categories of conduct and externalizing problems, characteristics typically associated with Oppositional Defiant Disorder, Conduct Disorder and ADHD.

“These are high level, chronic exposures that start before the child is even born, but continue throughout their life. More research is needed to examine the effects of cumulative exposure to phthalates on child development. But what this study suggests is that it’s not enough to regulate childhood exposure to these chemicals. The regulations need to include products that moms use,” said Dr. Engel.

Reference: The Mount Sinai Hospital / Mount Sinai School of Medicine, Mount Sinai finds prenatal exposure to certain chemicals affects childhood neurodevelopment, Jan. 28, 2010

Common plastics chemicals linked to ADHD symptoms



Are phthalates really safe for children? 

Phthalates are important components of many consumer products, including toys, cleaning materials, plastics, and personal care items. Studies to date on phthalates have been inconsistent, with some linking exposure to these chemicals to hormone disruptions, birth defects, asthma, and reproductive problems, while others have found no significant association between exposure and adverse effects. 

A new report by Korean scientists, published by Elsevier in the November 15th issue of Biological Psychiatry, adds to the potentially alarming findings about phthalates. They measured urine phthalate concentrations and evaluated symptoms of attention-deficit/hyperactivity disorder (ADHD) using teacher-reported symptoms and computerized tests that measured attention and impulsivity. 

They found a significant positive association between phthalate exposure and ADHD, meaning that the higher the concentration of phthalate metabolites in the urine, the worse the ADHD symptoms and/or test scores. 

Senior author Yun-Chul Hong, MD, PhD, explained that “these data represent the first documented association between phthalate exposure and ADHD symptoms in school-aged children.” John Krystal, MD, the Editor of Biological Psychiatry, also commented: “This emerging link between phthalates and symptoms of ADHD raises the concern that accidental environmental exposure to phthalates may be contributing to behavioral and cognitive problems in children. This concern calls for more definitive research.” 

The U.S. Centers for Disease Control and Prevention, in the Summary of their 2005 Third National Report on Human Exposure to Environmental Chemicals, state that “very limited scientific information is available on potential human health effects of phthalates at levels” found in the U.S. population. Although this study was performed in a Korean population, their levels of exposure are likely comparable to a U.S. population.

The current findings do not prove that phthalate exposure caused ADHD symptoms. However, these initial findings provide a rationale for further research on this association. 

Reference: Elsevier, Common plastics chemicals linked to ADHD symptoms, November 19, 2009

Pilot study relates phthalate exposure to less-masculine play by boys

When Boys turn into Girls A study of 145 preschool children reports, for the first time, that when the concentrations of two common phthalates in mothers’ prenatal urine are elevated their sons are less likely to play with male-typical toys and games, such as trucks and play fighting.

The University of Rochester Medical Center-led study is published in the International Journal of Andrology.

Because testosterone produces the masculine brain, researchers are concerned that fetal exposure to anti-androgens such as phthalates “which are pervasive in the environment“ has the potential to alter masculine brain development, said lead author Shanna H. Swan, Ph.D., professor of Obstetrics and Gynecology, director of the URMC Center for Reproductive Epidemiology, and an expert in phthalates.

“Our results need to be confirmed, but are intriguing on several fronts,” Swan said. “Not only are they consistent with our prior findings that link phthalates to altered male genital development, but they also are compatible with current knowledge about how hormones mold sex differences in the brain, and thus behavior. We have more work to do, but the implications are potentially profound.”

Phthalates are chemicals used to soften plastics. Recent studies have shown that the major source of human exposure to the two phthalates of most concern (DEHP and DBP) is through food. These phthalates are used primarily in polyvinyl chloride (PVC), so any steps in the processing, packaging, storage, or heating of food that use PVC-containing products can introduce them into the food chain.

Phthalates are also found in vinyl and plastic tubing, household products, and many personal care products such as soaps and lotions. Phthalates are becoming more controversial as scientific research increasingly associates them with genital defects, metabolic abnormalities, and reduced testosterone in babies and adults. A federal law passed in 2008 banned six phthalates from use in toys such as teethers, play bath items, soft books, dolls and plastic figures.

In Swan’s study, higher concentrations of metabolites of two phthalates, di(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP), were associated with less male-typical behavior in boys on a standard play questionnaire. No other phthalate metabolites measured in-utero was linked to the less-masculine behavior. Girls’ play behavior was not associated with phthalate levels in their mothers, the study concluded.

Swan’s interest in phthalates stems from an investigation into the environmental causes of reproductive health problems. Since 1998 she has led the federally funded, multi-center Study for Future Families (SFF), which established a large database from which to explore various scientific questions about toxins.

The current study focused on a small sample of SFF mothers who delivered children between 2000 and 2003. The mothers provided urine samples around the 28th week of pregnancy. The urine was analyzed for phthalate metabolites by the Centers for Disease Control and Prevention (CDC).

Swan hypothesized that phthalates may lower fetal testosterone production during a critical window of development – somewhere within eight to 24 weeks gestation, when the testes begin to function – thereby altering brain sexual differentiation.

To explore the question, researchers reconnected with mothers from the SFF sample and asked them to complete a standard research questionnaire, called the Preschool Activities Inventory (PSAI), for their children ages 3 1/2 to 6 1/2 years.

The PSAI is designed to discriminate play behavior within and between the sexes, and in the past has been shown to reflect the endocrine-disrupting properties of other toxins, such as PCBs and dioxins. The PSAI addressed three aspects of play: types of toys children choose (trucks versus dolls), activities (rough-and-tumble play, for example), and child characteristics.

However, researchers were concerned about how the choice of toys available in any given household might skew results, so in addition they asked about parental views toward atypical play. For example, the survey asked, “What would you do if you had a boy who preferred toys that girls usually play with?” The possible answers included “strongly encourage” (him to play this way) to “strongly discourage.”

The final survey scores are designed to reflect sex-typical play. Higher scores meant more male-typical play and lower scores meant more female-typical play.

Researchers then examined boys play-behavior scores in relation to the concentration of phthalate metabolites in their mothers’ prenatal urine samples, finding that higher concentrations of DEHP and DBP metabolites were associated with less masculine play behavior scores.

Earlier studies by Swan and others have shown that phthalate exposure during pregnancy might affect the development of genitals of both male rodents and baby boys. Scientists refer to this cluster of genital alterations as the “phthalate syndrome,” and research suggests that in rodent pups, the syndrome can have adverse consequences for later sexual development.

If endocrine disrupters such as phthalates can impair genital development and hormone levels in the body, the play-behavior study noted, then a deeper examination of how these chemicals impact the brain is warranted.

Reference: University of Rochester Medical Center, Pilot study relates phthalate exposure to less-masculine play by boys, Nov. 16, 2009

Exposure to phthalates may be a risk factor for low birth weight in infants

Phthalates are ubiquitous in newbornsMany parents worry about their child’s exposure to phthalates, the chemical compounds used as plasticizers in a wide variety of personal care products, children’s toys, and medical devices. Phthalate exposure can begin in the womb and has been associated with negative changes in endocrine function. A new study soon to be published in the Journal of Pediatrics examines the possibility that in utero phthalate exposure contributes to low birth weight in infants. Low birth weight is the leading cause of death in children under 5 years of age and increases the risk of cardiovascular and metabolic disease in adulthood.  

To investigate the associations between in utero phthalate exposure and low birth weight, Dr. Renshan Ge of the Population Council and colleagues from Fudan University and Second Military Medical University in Shanghai studied 201 pairs of newborns and their mothers between 2005 and 2006. Of the 201 infants studied, 88 were born with low birth weight. The researchers analyzed samples of the infants’ meconium, the first bowel movement that occurs after birth, and cord blood to determine phthalate levels.  

They found quantifiable levels of phthalate and phthalate metabolites in more than 70% of the samples. Infants with low birth weight had consistently higher levels of phthalates. According to Dr. Ge, “The results showed that phthalate exposure was ubiquitous in these newborns, and that prenatal phthalate exposure might be an environmental risk factor for low birth weight in infants.” Although these associations are not conclusive, this study supports the accelerating efforts to minimize phthalate exposure. 

Reference: The study, reported in “Phthalate Levels and Low Birth Weight: A Nested Case-Control Study of Chinese Newborns” by Zhang Y, PhD, Lin L, MD, Cao Y, PhD, Chen B, MD, Zheng L, MSC, Ge R, MD, appears in the Journal of Pediatrics, DOI 10.1016/j.jpeds.2009.04.007, published by Elsevier. EurekAlert, June 25, 2009.