Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure

Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 b...

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Published in:	Environmental health perspectives Vol. 113; no. 8; pp. 1056 - 1061
Main Authors:	Swan, Shanna H., Main, Katharina M., Liu, Fan, Stewart, Sara L., Kruse, Robin L., Calafat, Antonia M., Mao, Catherine S., Redmon, J. Bruce, Ternand, Christine L., Sullivan, Shannon, Teague, J. Lynn, The Study for Future Families Research Team
Format:	Journal Article
Language:	English
Published:	United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01-08-2005 National Institute of Environmental Health Sciences
Subjects:	Adusted gross income Chemical hazards Child, Preschool Children's Health Environmental health Environmental Pollutants - metabolism Environmental Pollutants - toxicity Female Genitalia Genitalia, Male - drug effects Genitalia, Male - growth & development Humans Infant Infants Male Maternal Exposure Metabolites Phthalates Phthalic Acids - metabolism Phthalic Acids - toxicity Pregnancy Prenatal Exposure Delayed Effects Rats Rodents Urine
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Summary:	Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2-36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 The Study for Future Families Research Team included, from the University of Missouri-Columbia: E.Z. Drobnis, B.S. Carter, D. Kelly, and T.M. Simmons. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center: C. Wang, L. Lumbreras, S. Villanueva, M. Diaz-Romero, M.B. Lomeli, and E. Otero-Salazar. Cedars-Sinai Medical Center: C. Hobel and B. Brock. University of Minnesota: C. Kwong and A. Muehlen. University of Iowa: A. Sparks, A. Wolf, J. Whitham, M. Hatterman-Zogg, and M. Maifeld. The authors declare they have no competing financial interests.
ISSN:	0091-6765 1552-9924
DOI:	10.1289/ehp.8100