September 17, 2014

expert reaction to phthalates in pregnancy and asthma in children

A study in the journal Environmental Health Perspectives has reported a link between prenatal exposure to phthalate and risk of asthma.

Prof Ieuan Hughes, Head of Pediatrics, University of Cambridge, said:

“The sample size of 300, set against asthma being very common in children, is a small number for this epidemiological study.

“There were a large number of variables and many women excluded from the study, so it is unclear how representative this study is of the normal population.

“The authors claim the relevance of these chemicals as being harmful to the fetus when the lung is developing – however, phthalate metabolite levels were measured from a spot urine test collected only 6-7 weeks before delivery; this will be of limited relevance to a developing lung which is all but developed at this stage of pregnancy.

“The authors have analysed their data by focusing on the extremes of the results (lowest vs highest chemical levels) and then use relative risks. A risk of 1 means there is no difference between two groups.  So the 72 and 78% figures of an increased risk (as portrayed by the authors to be alarming) are actually only plus 0.72 and plus 0.78, respectively. This is hardly worrisome in the context of chemicals that are ubiquitous in the environment.

“What about exposure?  The levels to which humans are exposed are much lower than those in animal studies to study the effects of chemicals such as phthalates and BPA. They have short half-lives and are rapidly cleared from the circulation. As to the fetus, there is the added protection of the placenta to guard against chemicals in the mother’s blood.

“It is noteworthy that the phthalate levels were no different in association with children who had a proper diagnosis of asthma versus those with asthma-like symptoms but not physician-proven to have asthma, so it is unclear how reliable the results are. It must also be emphasised that these results, if accepted to be robust, only show a possible association with asthma, NOT a cause of asthma.

“By their own admission, the authors state these results should be interpreted with caution.  I would add that pregnant women should not be unnecessarily alarmed by these results.”

Prof Jean Golding, Professor of Paediatric and Perinatal Epidemiology, University of Bristol, said:

“This is a very useful addition to the literature. Although a small study, it has the benefit of starting in pregnancy and collecting biological measures as the child progresses. The results concern a population of African-American and Dominican families living in New York. Its careful analysis of information provides evidence that exposure of the mother to specific phthalate chemicals during pregnancy may have a deleterious effect on the developing fetus. Moreover it adds some depth to an earlier study from the Children of the Nineties (ALSPAC) project involving over 7000 children which demonstrated that those whose mothers used the greatest levels of domestic chemical products in their homes were at increased risk of developing asthma. Whether or not the phthalates are causing asthma is not clear. This paper provides a small piece of evidence which needs to be confirmed in another study. Even if similar results are found, though, individuals exposed to one type of chemical are frequently exposed to many others, and untangling the possible causal pathways is for larger studies in the future.”

Prof Warren Foster, CIHR/Ontario Women’s Health Council Professor & Director, McMaster University, said:

“Overview: This paper describes a longitudinal study designed to evaluate the relationship between developmental exposure to phthalates and postnatal asthma in children. The study involved 300 pregnant inner city women from New York. 154/300 children were examined by a physician for wheeze or asthma. From this cohort 146 children were classified as non-asthmatic. Spot urine samples from the pregnant women were examined for phthalate metabolites using state of the art techniques. Results of the study revealed that developmental exposure to butylbenzyl phthalate (BBzP) and Di-n-butyl phthalate (DnBP) are associated with increased risk of current asthma in children. Metabolites for the other phthalates measured were not associated in asthma in this study.

“Impressions: Overall, the study has several strengths including the longitudinal study design and the sample size included. Physician examination and diagnosis of cases and controls is another strength of the study. Finally, the analytical methods and data analysis are appropriate for this sample.

“Weaknesses of the study include the reliance on single spot urine samples during pregnancy and lack of information concerning when in pregnancy these samples were collected for analysis. Phthalate exposure is wide spread and asthma was a common diagnosis in this population and thus the potential for finding associations is elevated by chance alone. Moreover, the study explored for potential associations between several different phthalates and asthma without correction for multiple independent comparisons thus increasing the likelihood for type I errors and spurious findings. Regardless, the data reveal a potential link between phthalate exposure and current asthma that requires further study. It is noted that this is but a single study that reveals a potential link between phthalate exposure and asthma whereas other studies, for multiple reasons, have not shown similar results. It also should be emphasized that causal associations are not demonstrated by this study. Therefore, it would be erroneous and thus misleading to conclude from this work that phthalate exposure causes asthma or augments the pathophysiology of asthma. Never-the-less this study has advanced an interesting proposal concerning phthalate exposure and inflammation that will require further investigation in carefully designed studies to establish this mode of action as both important and relevant.

“Implications: The data presented in this article will be of interest to regulatory bodies and toxicologists internationally. Although a solid contribution to the literature, the data presented in this study, on their own, are unlikely to affect regulator decisions and are of limited value to clinicians. Similarly, without independent confirmation of the results by additional epidemiological studies and further mechanistic insight from animal and tissue culture studies, it is proposed that the data are of very limited value to the public.”

Prof Andrew Bush, Professor of Paediatrics and Head of Section (Paediatrics) at Imperial College London; Professor of Paediatric Respirology at the National Heart and Lung Institute; and Consultant Paediatric Chest Physician at the Royal Brompton & Harefield NHS Foundation Trust, said:

“As the authors themselves state, this relatively small study requires confirmation in a larger cohort and among a different group of people; and it should be noted it is in a subgroup of a larger study, raising the question as to whether despite the authors’ best efforts, this could be a biased sample.  While the possible association between phthalate exposure in pregnant women and asthma risk in their children is of potential interest, this is a preliminary study that should not become the basis of any health recommendations.  Pregnant women should not worry about this potential association – no plausible biological mechanism has been put forward, and there is certainly no suggestion that phthalate exposure causes increased asthma risk.”

‘Asthma in Inner-City Children at 5-11 Years of Age and Prenatal Exposure to Phthalates: The Columbia Center for Children’s Environmental Health Cohort’ by Robin M. Whyatt et al. published in Environmental Health Perspectives on Wednesday 17 September 2014.

Declared interests

Dr Warren Foster: “I have not published with any of the authors on this paper. My research funding is in areas unrelated to the issue addressed in this paper. I am frequently invited to provide advice to research grant councils, industry, non-government organizations, and government bodies locally, nationally, and internationally on issues of toxicology and women’s health. I do not currently work with phthalates or research in the area of asthma.”