Associations of Maternal Pregnancy Urine Estrogen Levels with Phthalate and Phthalate Replacement (1,2-Cyclohexane Dicarboxylic Acid Diisononyl Ester, DiNCH) Metabolites

摘要

Rationale: Pregnant women are exposed to phthalates in food, personal care and household products. Phthalates alter estrogen levels in experimental models but their potential to impact levels in human pregnancy is not well characterized. Methods: 291 participants in an Illinois pregnancy cohort collected 5 urines across pregnancy for pooling and quantification of 16 phthalate/DiNCH metabolites. Exposures were expressed as the molar sum of metabolites for: ΣDiNCH, ΣDEHP, ΣDBP, ΣDiBP, ΣDiNP, ΣPCP, and ΣAA (respective personal care product and anti-androgenic phthalates). At 10-14, 28-30 and 34-36 gestational weeks (GW), urine estradiol, estrone, estriol and metabolites were measured and summed (ΣE). Specific gravity adjusted exposure and ZE data were log-transformed. Linear mixed-effects models assessed relationships of phthalates/ΣDiNCH with ΣE controlling for fetal sex, maternal age, pre-pregnancy BMI, ΣE analytic batch, and GA at urine collection for ΣE evaluation. Interactions of phthalates/ΣDiNCH, fetal sex, ΣE batch, and GA at ZE urine collection were explored. Results: Participants were 82% white, 72% had income >$60,000/yr, 84% had a college+ education, and urine biomarker levels were similar to U.S. women. At 10-14 weeks, ZE increased with increasing: ΣDBP (b=1.5, 95% Cl=0.5, 2.5), ΣDiNP (b=1.3, 95% Cl=0.6, 2.0), ΣPCP (b=0.5, 95% Cl=0.1, 0.8), and ΣAA (b=0.4, 95% Cl=0.01, 0.7); associations in late pregnancy were attenuated and non-significant. ΣE increased with increasing ΣDEHP in women carrying females (b=0.7, 95% Cl=0.2, 1.3) and ΣDiBP in women carrying males for ΣE measured in only one analytic batch. ΣE was not associated with ΣDiNCH. Conclusions: ΣDBP, ΣDiNP, ΣPCP, and ΣAA phthalates were associated with higher gestational ΣE in early but not later pregnancy. For other phthalates, associations were only in small sub-group analyses. Whether pregnancy estrogen levels mediate associations between phthalates and pregnancy outcomes merits investigation.