Influence of race on prenatal phthalate exposure and anogenital measurements among boys and girls

Background: Select phthalates have antiandrogenic activity, which raises concern for adverse developmental outcomes given widespread exposure of pregnant women. Investigators have reported associations between maternal urinary phthalates and altered anogenital distance (AGD), a marker of in utero androgen activity, among offspring. However, data assessing the impact of race on these associations is sparse. Objectives: To evaluate associations between prenatal phthalate exposure and AGD in a racially diverse newborn population. Methods: We prospectively collected second trimester urine from 187 African American and 193 white mothers, and used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure eight phthalate metabolites and calculate molar sums. We measured anopenile (APD) and anoscrotal (ASD) distances of 171 boys and anoclitoral (ACD) and anofourchette (AFD) distances of 128 girls at delivery. We collected sociodemographic and clinical data from questionnaires and delivery records. Results: We identified a statistically significant inverse association for mono-2-ethylhexyl phthalate (MEHP) and APD in boys (B = -1.57 mm, p = 0.02), which was stronger for African Americans (B = -2.07 mm, p = 0.04) than for whites (B = -1.23 mm, p = 0.22), although the racial interaction was not statistically significant (p = 0.56). We found a longer ASD for higher molar sums of dibutyl phthalate (Sigma DBP; B = 0.99 mm, p = 0.04), with stronger associations for whites (B = 1.30 mm, p = 0.04) than for African Americans (B = 0.39 mm, p = 0.59), again without a statistically significant racial interaction (p = 0.34). Among girls, we found inverse associations for tertiles of MEHP with AFD and ACD, and statistically significant race-based interactions, in which ACD was longer for whites and shorter for African Americans, following exposure to monoethyl phthalate (MEP; p = 0.01) and SDBP (p = 0.08). Conclusions: Our findings suggest race and sex play important roles in phthalate-associated reproductive developmental toxicity, with important implications for designing future investigations and health interventions.