Association of blood isobutyronitrile with infertility among reproductive-aged women: Results from the NHANES cohort

Isobutyronitrile finds extensive application in organic synthesis for the production of the insecticide diazinon. Apart from occupational exposure, cigarette smoking may also expose the general population to isobutyronitrile. However, to date, the association between isobutyronitrile and female infertility has not been explored in a population-based study. Hence, we analysed data from 1254 women, aged 18–44, with blood isobutyronitrile results and infertility questionnaires, from National Health and Nutrition Examination Survey (NHANES) 2015–2016 and NHANES 2017-March 2020. To compare differences, weighted chi-square tests were conducted for categorical variables and weighted regression models were performed for continuous variables. Logistic regression and generalized linear models were applied to examine the associations. Each standard deviation increment (SD=0.026) of isobutyronitrile increased the risk of infertility by 24 % after adjusting for potential confounders in logistic regression model (aOR=1.24; 95 % CI: 1.06–1.46). In women who had been pregnant and gave birth, the results exhibited a consistent linear relationship. The participants were classified into two groups, namely positive and negative, using an isobutyronitrile cut-off value that exceeded 0.040 ng/mL. The positive group did not demonstrate a statistically significant correlation (aOR=1.55; 95 % CI: 0.66–3.65). According to smooth curve fitting, isobutyronitrile and infertility was linearly related across the entire range, and no threshold effect was found. Particularly, non-Hispanic Black women had a significantly stronger association with isobutyronitrile exposure and infertility (aOR=4.27; 95 % CI: 1.32–13.83). In conclusion, our study was the first report of an independent association of isobutyronitrile with infertility, especially in non-Hispanic Black women. Additional fundamental research on nonhuman primates, along with comprehensive clinical studies, are necessary to fully elucidate the intricate mechanisms underlying isobutyronitrile activity.