January 27, 2006
A leading scientific research firm has given a failing grade to a recent study by Shanna Swan and others that claimed prenatal exposure to phthalates affected the reproductive development of infant boys. The review of the Swan paper by Exponent Inc. concludes that the hypothesis of the Swan team “is not supported,” because it fails on five key counts, detailed below.
In an attempt to resolve the apparent problems with the published report, the Exponent team asked Dr. Swan by personal letter to explain her methodology and to provide her full set of data, but both requests were refused.
“It is fundamental to the progress of science for researchers to provide others with the opportunity to either confirm or refute published findings,” said Marian Stanley, Manager of the Phthalate Esters Panel, which commissioned the Exponent study. “The unwillingness to release all of the data to scientific reviewers raises serious questions about the quality of the study.”
In the Swan study, single urine samples were collected from pregnant women, and the levels of metabolites of various phthalates were measured. Boys born to these women were later measured at varying ages for their AGD, or anogenital distance, which is the distance from the anus to the base of the penis. In an attempt to compensate for the varying ages of the infants, the Swan researchers divided the AGD by the infant’s weight and called the results an AGI, or anogenital index. They then compared the AGI measurements with phthalate metabolite levels in urine samples from the mothers, and reported a statistical correlation between the levels of metabolites of four phthalates and the AGI. They also attempted to relate AGI to certain genital effects (penis size and occurrence of undescended testicles), while stating these changes were “subtle” and could not be considered either genital malformations or damage (a qualifier largely ignored by the media in reporting on the study).
The report has come under serious criticism by experts in statistics, toxicology and pediatrics. Recently, a government panel reviewing a particular phthalate reported it was unable to duplicate the Swan paper’s mathematical computations that allegedly showed a correlation between AGI and genital effects. Dr. Swan has since stated to a reporter that she is submitting a letter of “clarification” to the journal that published her paper, but it is not clear what she is clarifying.
The Exponent team reported five major flaws in the Swan study:
- The urine samples collected from the pregnant women are neither reliable nor valid for measuring their exposure to phthalates. The samples taken were not adjusted for variable fluid intake, were not adjusted for the time of day the samples were taken, and otherwise did not follow standard procedures, making the samples useless for obtaining accurate measurements of phthalate exposures.
- The AGD measurement is of no known significance in humans. It is not a standard measurement in the practice of medicine and has never been related to any reproductive system problems. It is also difficult to measure accurately. Twenty per cent of the boys measured were dropped from the analysis because the researchers judged that reliable measurements could not be obtained for those boys. It is quite possible that many of the measurements on the remaining 80 percent also were not accurate.
- Converting the AGD to an AGI was an attempt to correct for varying weight and age, but ignores the fact that while the AGD does change with those two variables, the changes are not linear, and the correction is therefore incorrect. Also, the researchers did not compensate for other variables, like height or premature birth, in the infant’s history.
- In addition to the normal variations in weight and age, some measured infants were pre-term or even premature (which could well affect variables such as AGD, and genital effects), but were not excluded from the study.
- It appears the researchers used the wrong statistical model to get their results. The statistical association claimed by the researchers is based on a model that predicts a relatively rapid decrease in AGI at low phthalate levels and much smaller decreases at higher levels. But this relationship is not biologically plausible; it should be the other way around. Thus, the Exponent researchers question the results of a study that used a model that is probably wrong.
“This Exponent report, combined with a critique just published in Environmental Health Perspectives (see http://ehp.niehs.nih.gov/docs/2005/8688/letter.html#lett,) and the government panel’s report that some of the Swan study’s math is wrong, should give pause even to the report’s propagandists,” said Ms. Stanley. “Those who are using the Swan report to stampede federal and state governments into creating new barriers to the use of phthalates—a group that includes its principal author – may be serving their own goals, but they are not serving science or the public well.”
