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Decrease in anogenital distance among male infants with prenatal phthalate exposure
Environmental Health Perspectives, August, 2005 by Shanna H. Swan, Katharina M. Main, Fan Liu, Sara L. Stewart, Robin L. Kruse, Antonia M. Calafat, Catherine S. Mao, J. Bruce Redmon, Christine L. Ternand, Shannon Sullivan, J. Lynn Teague
Newborn male rodents have no scrotum, and the external genitalia are undeveloped; only a genital tubercle is apparent for both sexes. The distance from the anus to the insertion of this tubercle, the AGD, is androgen dependent and about twice as long in males as in females. The AGD has been shown to be a sensitive measure of prenatal antiandrogen exposure (Rhees et al. 1997). Recently, Salazar-Martinez et al. (2004) studied AGD in 45 male and 42 female infants. They measured the distance from the anus to the base of the scrotum in males and from the anus to the base of the genitals (the fourchette) in females. By these measures, AGD was sexually dimorphic and about twice as long in males as in females. No other studies have examined AGD among human males, although two other studies have evaluated AGD in female infants (Callegari et al. 1987; Phillip et al. 1996).
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Materials and Methods
Study participants. Women included in our study were originally recruited into the first phase of the Study for Future Families (SFFI), a multicenter pregnancy cohort study, at prenatal clinics in Los Angeles, California (Harbor-UCLA and Cedars-Sinai), Minneapolis, Minnesota (University of Minnesota Health Center), and Columbia, Missouri (University Physicians), from September 1999 through August 2002. Data collection is still ongoing in Iowa, where a center was added late in SFFI, so Iowa participants are not included in this analysis. Methods are described in detail elsewhere (Swan et al. 2003). Briefly, couples whose pregnancy was not medically assisted were eligible unless the woman or her partner was < 18 years of age, either partner did not read and speak Spanish or English, or the father was unavailable or unknown. All participants completed a questionnaire, most gave blood samples, and after urine collection was added midway through the study, most also gave a urine sample.
Eighty-five percent of SFFI participants agreed to be recontacted, and we invited these mothers to take part in our follow-up study. The family was eligible for the follow-up study (SFFII) if the pregnancy ended in a live birth, the baby was 2-36 months of age, and the mother lived within 50 mi of the clinic and could attend at least one study visit. Here we report on results from the first study visit only. Human subject committees at all participating institutions approved SFFI and SFFII, and all participants signed informed consents for each study.
Physical examination. After standard anthropometric measurements (height, weight, head circumference, and skin-fold thickness) were obtained, a detailed examination of the breast and genitals was conducted under the supervision of pediatric physicians who were trained in its administration. Every attempt was made to standardize the examination, which was developed specifically for this study. These methods included training sessions before and during the study and the use of standardized equipment. Neither the pediatric physicians nor the support staff had any knowledge of the mother's phthalate concentrations.
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