Phthalate Exposure and Suggested Male Reproductive Development
Recently, there has been a lot of public concern raised about exposure to some phthalates, based on reports of developmental effects in male infants born to mothers who were exposed during pregnancy. These reports from the research of Dr. Shanna Swan1 and others are quite controversial in the scientific community. The researchers originally published an article in 2005 suggesting that maternal exposure to certain phthalates resulted in a “subtle” difference in the genitalia of male infants. It is important to note that it is not clear that the physical effect described in this research is outside the normal differences in any group of infant boys, as there was no control group.
Dr. Swan was among the authors of a commentary on this research in 2006 and she authored an additional article in 2008 that, in part, reanalyzed the data presented in the earlier publications. In 2009, Dr. Swan and her colleagues published a report suggesting reduced “male play behavior” in these same young boys.
By All Measured Parameters, the Boys Were Normal
In the original 2005 publication, Dr. Swan and her colleagues indicate that, by all measured parameters, the boys’ genitalia were normal. They suggested, however, that a reduction in the anogenital index (or AGI) among male offspring of women with higher urinary concentrations of four phthalate metabolites was suggestive of an adverse effect on male reproductive development. The researchers created the AGI in an attempt to standardize measurement of the distance between the anus and the scrotum in infant boys ranging in age from newborn to 18-months-old by incorporating consideration of the boys’ weight.
“Novel Index” Has Not Been Replicated
In evaluating the finding in a review of some phthalates, an expert panel of the National Toxicology Program (NTP) considered the AGI measurement developed by Dr. Swan to be a “novel index” whose relevance in humans “has not been established.” To date, Dr. Swan’s results have not been repeated by other researchers and Dr. Swan has declined requests by other scientists to review her data.
In reviewing the 2005 publication, Drs. Gerard McEwen and Gerald Renner wrote –
“[a]ll male infants evaluated in the study appeared normal (Swan et al. 2005). Therefore, there is no evidence for potential adverse effect in the test population. Because little is known about AGD in human infants and its variation, no conclusion can be drawn whether the reported values are normal or abnormal. The range of AGD values seen among study subjects likely represents typical biologic variation that would be expected to occur among normal study subjects.”
In a follow-up study published in 2009, Dr. Swan and her colleagues asked mothers who had participated in the 2005 study to now evaluate the play habits of their sons. Although they used a standard questionnaire about the child’s choice of toys, activities and type of play – the Preschool Activities Inventory (PSAI) – the researchers indicate in the paper that the questionnaire was altered for the study to incorporate “parental attitudes about male behavior,” and to eliminate some questions. The authors themselves note that such adjustments “have not been used previously” in evaluating PSAI results and that they “remain to be validated.”
Despite this astonishing acknowledgement, Dr. Swan suggests that the mothers’ exposure to two phthalates was significantly associated with less masculine play behavior in boys. As with her 2005 study, Dr. Swan’s use of unvalidated methodologies and unconventional data analysis have been criticized by the scientific community. Dr. Swan has subsequently acknowledged that “[t]he study needs to be replicated at a larger scale in a different population.”
Criticism about Dr. Swan’s 2009 study has come from a variety of sources, including the following:
NHS Choices, a publication of Britain’s National Health Services, indicated: “The limitations of this research mean that this evidence alone is too weak to form any definite conclusions, and parents should not be concerned about claims of “gender-bending” phthalates affecting their children’s brains or habits.” -- NHS Choices
Trevor Butterworth, editor, STATS.org: said “So what the reports failed to mention was the weak statistical data the authors of the study employed to reach this conclusion--after using an unvalidated methodology to collect it, which, for good measure, may also have been contaminated by survey bias.” -- Forbes
The British Plastics Federation (BPF) spokesperson said: “The British Plastics Federation urges great caution when assessing the results of the study. The author’s recognition that the study’s results are ‘not straightforward’ is an understatement. This study uses a relatively small sample and a simplistic approach which has produced conclusions that fly in the face of the body of scientific evidence.” -- Plastics & Rubber Weekly
Dr. Elizabeth Whelan, President, American Council on Science and Health, said: “If this sounds absurdly unscientific to you, it's because it is …Shanna Swan has made a career out of studying phthalates and trying to find reproductive effects from them… This is junk science at its worst.” -- FOXBusiness
Dr. Sheela Sathyanarayana, assistant professor of pediatrics at the University of Washington: “There are other caveats to the research. The number of boys in the study is very small and it's not clear if the difference between the boys is significant.” -- HealthDay Reporter
“Educated Guesses Dressed Up in Evening Clothes"
Dr. Swan is no stranger to generating scientific controversy, and her methodologies have long been criticized. Her expert testimony played a pivotal role in the landmark Supreme Court ruling in Daubert v. Merrell Dow Pharmaceuticals, Inc (1993) that established the standard for admitting expert testimony in federal courts. In upholding the lower court’s ruling that testimony by Dr. Swan and other witness was inadmissible, the Court cited the lower court’s conclusion that “expert opinion based on a scientific technique is inadmissible unless the technique is generally accepted as reliable in the relevant scientific community.” The Court ruling further opined that “expert opinion based on a methodology that diverges significantly from the procedures accepted by recognized authorities in the field cannot be shown to be generally accepted as a reliable technique.”
In a similar fashion Dr. Swan's expert testimony was ruled inadmissible in Hall v. Baxter Healthcare (1996), where the U.S. District Court for the District of Oregon described Dr. Swan’s testimony as "no more than educated guesses dressed up in evening clothes."
1Shanna Swann, Ph.D., is director of the Center for Reproductive Epidemiology at the University of Rochester School of Medicine and Dentistry.