Longitudinal biomonitoring of mycotoxin exposure during pregnancy in the Yale Pregnancy Outcome Prediction Study

Abstract

Mycotoxins are fungal toxins that may trigger adverse health effects in pregnant women and their unborn children. Yet, data is scarce on the dynamic exposure patterns of mycotoxins in pregnant women, especially in the United States. This study assessed mycotoxin exposure profiles in women (n = 50) from the Yale Pregnancy Outcome Prediction Study (YPOPS) cohort at four distinct time points. Multi-analyte human biomonitoring assays based on liquid chromatography tandem mass spectrometry (LC-MS/MS), were developed for human serum and plasma matrices. The serum method was applied, together with an established urine method, to quantify mycotoxin levels in longitudinally collected matched serum (n = 200) and spot urine (n = 200) samples throughout pregnancy. The serum samples were mostly contaminated by the potential carcinogen ochratoxin A (detection rate: 46 %; median: 0.09 ng/mL), the hepato- and nephrotoxic citrinin (detection rate: 32 %; median: 0.02 ng/mL) and two enniatins (EnnB; detection rate: 97 %; median: 0.01 ng/mL and EnnB₁; detection rate: 12 %; median: 0.003 ng/mL) which may act as immunotoxins. The most prevalent mycotoxins quantified in urine included deoxynivalenol (detection rate: 99 %; median: 23 ng/mL), alternariol monomethyl ether (detection rate: 69 %; median: 0.04 ng/mL), and zearalenone (detection rate: 63 %; median: 0.16 ng/mL). Seven other biomarkers of exposure including the highly estrogenic α-zearalenol and genotoxic Alternaria toxins, were also determined. Carcinogenic aflatoxins were not detected in any of the samples. Exposure assessment was based on the urinary data and performed by calculating probable daily intakes and comparing the human biomonitoring guidance value (HBM-GV) for deoxynivalenol. The results showed that the individuals exceeded the tolerable daily intake for deoxynivalenol and zearalenone on average at 28 % and 2 % over the different time points. Using the HBM-GV approach, the average exceedances for deoxynivalenol increased to 48 % indicating high exposure. For all the samples in which ochratoxin A was quantified, the estimated margin of exposure for neoplastic effects was below 10,000, indicating possible health concerns. Overall, this study showed that pregnant women were exposed to several regulated and emerging mycotoxins and that exposome-scale assessment should be a future priority in susceptible populations to better characterize xenobiotic exposure.