Maternal and paternal serum concentrations of perfluoroalkyl and polyfluoroalkyl substances and the secondary sex ratio

Select persistent environmental chemicals have been associated with a reduction in the secondary sex ratio (SSR), or the ratio of male to female live births. We evaluated preconception maternal, paternal, and couple serum concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in relation to the SSR, given the absence of previous investigation. Two hundred thirty-three couples from Michigan and Texas were enrolled prior to conception and prospectively followed through delivery of a singleton birth, 2005-2009. Maternal and paternal serum concentrations (ng mL(-1)) were measured at baseline for seven PFASs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a male birth, after adjusting for potential confounders. When maternal and paternal PFAS concentrations were modeled jointly, five of the seven PFASs, including the two most prominent PFASs, perfluorooctane sulfonic acid and perfluorooctanoic acid, were not significantly associated with the SSR. However, paternal N-methyl-perfluorooctane sulfonamidoacetic acid (MeFOSAA) and perfluorononanoic acid (2nd versus 1st tertile, OR, 0.43, 95% CI, 0.21-0.88) were significantly associated with an excess of female births. Meanwhile, a dose-response relation was observed only for paternal MeFOSAA (2nd versus 1st tertile, OR, 0.53, 95% CI, 0.26-1.10; 3rd versus 1st tertile, OR, 0.34, 95% CI, 0.13-0.89). This study suggests a possible dose-response relation between a less prevalent PFAS and a reversal in the SSR, though the underlying mechanisms remain unknown and the findings await corroboration to eliminate other explanations including chance.