Maternal mycoestrogen exposure in relation to timing of birth and placental corticotropin releasing hormone concentrations in a U.S. pregnancy cohort.

Zearalenone (ZEN) is a mycotoxin that widely contaminates human food supplies. In animal models, exposure to ZEN has extensive impacts on reproduction and pregnancy including contributing to early parturition. Here, we translate that research to humans by examining gestational exposure to ZEN in relation to the timing of birth and placental corticotropin releasing hormone (pCRH), a hormone that regulates the timing of parturition. Utilizing data from a pregnancy cohort (UPSIDE; Rochester, NY; n = 299), we investigated exposure to ZEN and its metabolites in relation to: 1) gestational age at birth; and 2) pCRH across pregnancy. Adjusted linear regression models were fitted to examine gestational age at birth and pCRH in relation to three maternal urinary mycoestrogen measures in each trimester: (1) ZEN; (2) its metabolite, α-zearalenol (aZOL); and (3) the sum of ZEN and its five metabolites (∑mycoestrogens). For models examining pCRH, we additionally fitted linear mixed effects models to account for repeated measures. All models were refitted stratified by fetal sex. Mycoestrogens were detected in over 90% of samples in each trimester. Sex-stratified analyses showed distinct sex differences in trimester 2 in relation to exposure, with higher gestational age at birth in males (β:2.35 days, 95%CI:0.14, 4.56) and lower gestational age at birth in females (β:-1.70 days, 95%CI:-3.35, -0.07). In linear mixed effects models examining pCRH, ZEN was positively associated with pCRH concentrations: ZEN (%Δ:5.17, 95%CI:1.09, 9.36). Mycoestrogen exposure may be associated with sex-specific changes in gestational age at birth and higher pCRH, a risk factor for preterm birth.