title: Decrease in anogenital distance among male infants with prenatal phthalate exposure.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York [corrected] USA. shanna_swan@urmc.rochester.edu
authors.forename: Shanna H
authors.initials: SH
authors.lastname: Swan
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Sara L
authors.initials: SL
authors.lastname: Stewart
authors.forename: Robin L
authors.initials: RL
authors.lastname: Kruse
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Calafat
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Mao
authors.forename: J Bruce
authors.initials: JB
authors.lastname: Redmon
authors.forename: Christine L
authors.initials: CL
authors.lastname: Ternand
authors.forename: Shannon
authors.initials: S
authors.lastname: Sullivan
authors.forename: J Lynn
authors.initials: JL
authors.lastname: Teague
mesh_terms: D002675:Child, Preschool; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure; D010795:Phthalic Acids / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D004785:Environmental Pollutants; D010795:Phthalic Acids