Background Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here, we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs). Methods Phthalate metabolites [including those of diethylhexyl phthalate (DEHP) and their molar sum (ΣDEHP)] were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as 'lower' and 'higher' stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress group) using adjusted multiple regression interaction models. Results In the lower stress group, first trimester ΣDEHP was inversely associated with two measures of male AGD: Anoscrotal distance (AGD-AS; β = -1.78; 95% CI -2.97, -0.59) and anopenile distance (AGD-AP; β = -1.61; 95% CI -3.01, -0.22). By contrast, associations in the higher stress group were mostly positive and non-significant in male infants. No associations were observed in girls. Conclusions Associations between prenatal phthalate exposure and altered genital development were only apparent in sons of mothers who reported no SLEs during pregnancy. Prenatal stress and phthalates may interact to shape fetal development in ways that have not been previously explored.
Bibliographical noteFunding Information:
We thank the TIDES Study Team for their contributions. Coordinating Center: Fan Liu, Erica Scher; UCSF: Marina Stasenko, Erin Ayash, Melissa Schirmer, Jason Farrell, Mari-Paule Thiet, Laurence Baskin; UMN: Heather L. Gray Chelsea Georgesen, Brooke J. Rody, Carrie A. Terrell, Kapilmeet Kaur; URMC: Erin Brantley, Heather Fiore, Lynda Kochman, Jessica Marino, William Hulbert, Robert Mevorach, Eva Pressman; UW/SCH: Richard Grady, Kristy Ivicek, Bobbie Salveson, Garry Alcedo; and the families who participated in the study. In addition, we thank Antonia Calafat (Centers for Disease Control) for urinary phthalate metabolite analyses, Dr Sally Thurston (URMC) for statistical advice, the TIDES families for their participation, and the residents at URMC and UCSF who assisted in birth exams. Funding for TIDES was provided by the following grants from the National Institute of Environmental Health Sciences: R01ES016863-04 and R01 ES016863-02S4. Funding for the current analysis was provided by K12ES019852-01.
- anogenital distance
- endocrine disrupting chemicals