Prenatal exposure to mycoestrogens in relation to early childhood neurodevelopment in a U.S. pregnancy cohort

Zearalenone (ZEN) is a ubiquitous mycotoxin that contaminates global food supplies. In the U.S., biomonitoring studies suggest widespread exposure to ZEN and its metabolites, collectively referred to as “mycoestrogens.” Extensive animal literature, alongside human studies, implicates ZEN as a potential contributor to adverse pregnancy and fetal outcomes. To our knowledge, no studies have investigated mycoestrogen exposure in relation to neurodevelopment. Here, we examine associations of prenatal mycoestrogen exposure with childhood neurodevelopmental outcomes. Utilizing data from a U.S. pregnancy cohort (UPSIDE; Rochester, NY; n = 215), we examined three mycoestrogen measures (ZEN; its metabolite alpha-zearalenol, aZOL; and a composite sum of ZEN and five metabolites, ∑mycoestrogens) in relation to two neurodevelopmental measures: (1) Language and Cognition sub-scores of the Bayley Scales of Infant Development at 6, 12, and 24mos and (2) Snack Delay Test for inhibitory control at 24mos. Mycoestrogens were measured in urine samples from each trimester (T1-3) using LC-MS/MS. Adjusted multivariable linear and Poisson regression models were fitted for analyses examining Bayley and inhibito​ry scores as outcomes, respectively. All models were refitted stratified by infant sex. In females, a log-unit increase in mycoestrogens was associated with a lower cognition score at 24mos (∑mycoestrogens: β:-2.67, 95%CI:-5.25, -0.10; ZEN: β:-5.37; 95%CI:-8.87, -1.87). Few associations were observed in males aside from positive associations between T1 ZEN and aZOL exposure and language scores at 6mos (ZEN: β:3.30, 95%CI:0.368, 6.23; AZOL: β:3.10, 95%CI:0.02, 6.19). For inhibitory control, across all children, a log-unit increase in T1 ZEN was associated with a 17% lower rate of succeeding in successive trials (95% CI: 0.72, 0.96). Mycoestrogens may be associated with adverse effects on neurodevelopmental outcomes, particularly in females. This study provides the first evidence that mycoestrogens may impact neurodevelopment in children. Not applicable.