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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

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We then examined models that included individual phthalate metabolites. Other than age and age squared, no covariates altered regression coefficients for the phthalate metabolites by > 15%, and none were included in final models. All regression coefficients for individual metabolites (logarithmically transformed to normalize distributions) were negative (Table 4). MEP, mono-n-butyl phthalate (MBP), MBzP, and monoisobutyl phthalate (MiBP) were (inversely) related to AGI; p-values for regression coefficients were between 0.007 and 0.097. We also measured three metabolites of DEHP. Although the hydrolytic monoester metabolite mono-2-ethylhexyl phthalate (MEHP) was unrelated to AGI [regression coefficient = -0.05; 95% confidence interval (CI), -0.53 to 0.43], regression coefficients for the oxidative monoester metabolites of DEHP, mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) were of a magnitude comparable with those for MEP and MBzP (p-values = 0.114 and 0.145 for MEOHP and MEHHP, respectively). AGI appeared to be independent of the concentrations of monomethyl phthalate (MMP) and MCPP, metabolites of dimethyl phthalate and di-n-octyl phthalate, respectively.

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Categorical analyses. The 25 boys with AGI below the 25th percentile for age were classified as having a short AGI. This group had an AGI that was, on average, 18.3% (range, 10-32%) shorter than expected based on the final regression model. Boys with AGI [greater than or equal to] 75th percentile of expected were classified as having a long AGI, and boys with AGI between the 25th and 75th percentile of expected were considered intermediate. Boys' weight and age did not differ appreciably among these groups.

Table 5 shows mean and median values for the AGI-associated metabolites for boys in the short, intermediate, and long categories of AGI. We calculated the ORs for short AGI for each monoester metabolite (Table 6). For high compared with low concentration of MBP, the OR for a short AGI was 10.2 (95% CI, 2.5 to 42.2), whereas for medium concentration compared with low the OR was 3.8 (95% CI, 1.2 to 12.3). The corresponding ORs for high compared with low concentration of MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05).

Other genital parameters. Degree of testicular descent was associated with AGD (R = 0.20, p = 0.02). The proportions of boys with one or both testicles incompletely descended were 20.0, 9.5, and 5.9% for boys classified as having short, intermediate, and long AGI (p-value for short AGI compared with all other boys < 0.001). The proportion of boys with a scrotum categorized as small and/or "not distinct from surrounding tissue" was also elevated for boys with short AGI (p < 0.001). AGD was significantly associated with penile volume (R = 0.27, p = 0.001), and penile volume divided by weight was correlated with AGI (R = 0.43, p = 0.001). Testicular volume, which was measured by orchidometer, is not shown here because participating physicians considered the measurement to be unreliable--a decision made before analyses of phthalate exposure.

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

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