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

Results

The population for the present analysis was identified from families recruited in California, Minnesota, or Missouri for whom data entry was complete by 17 December 2004, the cutoff date for the present analysis. At that time, 654 participants from these three centers had completed SFFI and given permission to be recontacted. Of these, 477 (72.9%) were eligible for SFFII and 346 (72.5%) participated (Table 1). SFFII participants were demographically similar to nonparticipants except that nonparticipants were more likely to be Hispanic because of a lower eligibility rate (60%) in CA, where most participants were Hispanic. Of the 172 boys born to these mothers, we excluded 5 boys in twin births, 10 boys with incomplete data, and 23 boys for whom AGD was not recorded [two whose mothers declined the genital exam, with the remainder older boys (mean age, 19.6 months), for whom the study examiner felt the measurement was not reliable, usually because of the boys' activity level]. The remaining 134 boys comprise the sample used for the analysis of AGD and other genital measurements. Among the 134 boys for whom we have genital measurements, no frank genital malformations or disease were detected, and no parameters appeared grossly abnormal. The mean age at first examination was 15.9 months, and mean weight was 10.5 kg (Table 2). Mean ([ or -] SD) AGD was 70.3 [ or -] 11.0 mm, with a distribution that was well approximated by a normal curve. Overall, 86.6% of boys had both testes classified as normal or normal-retractile.

A prenatal urine sample was assayed for phthalate metabolites for mothers of 85 of these boys. These mother-son pairs comprise the data set for the analysis of AGD and phthalate metabolite concentration. Because urine collection began midway through SFFI, mothers with a stored urine sample were recruited later in the study, and their sons tended to be younger at examination (mean age, 12.6 months; interquartile range, 5-16 months). Summary statistics for all boys included in the analysis of physical measurements, and the subset of boys for whom mothers' prenatal phthatate concentrations were also available are shown separately in Table 2.

All phthalate metabolites tested were above the LOD in > 49% of women, and most tested were above the LOD in > 90% of the samples (Table 3). Concentrations spanned four orders of magnitude, from below the LOD (estimated value = 0.71 ng/mL) to 13,700 ng/mL for MEP. Means ranged from 2.68 for mono-3-carboxypropyl phthalate (MCPP) to 629.8 for MEP. Three of the four AGI-associated metabolites (other than MEP) were significantly correlated (p < 0.005).

Regression analyses. We initially modeled AGD as a linear function of age and weight, but this model fit poorly (adjusted [R.sup.2] = 0.22). We found that using AGI (AGD/weight) as a function of age provided the best fit, as has been shown in rodent models (Vandenbergh and Huggett 1995). The best-fitting model for AGI includes linear and quadratic terms for age and is given by AGI = 10.8835 - 0.3798 (age) 0.0068 ([age.sup.2]) (adjusted [R.sup.2] = 0.61). Using this model, we calculated mean AGI and its 5th, 25th, 75th, and 95th percentiles (Figure 1).