Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are chemicals widely used in industrial and household products. Because of their persistence, bioaccumulation, and toxic properties, PFASs have been recognized as emerging environmental pollutants. Therefore, several actions have been taken by industry and regulators to phase-out the production of some commonly detected long-chain PFASs. As a consequence, the production of these chemicals has shifted from developed countries toward developing countries, especially China. The most developed city in China, Shanghai, has the highest concentrations of PFASs in the soil, sediment, and surface water. Besides shifted countries of production, many manufacturers have begun to produce and use short-chained PFASs, such as perfluorobutane sulfonate (PFBS) as a replacement for PFOS. PFBS is also persistent and bioaccumulative. Additionally, the water-solubility of PFBS is higher than PFOS, which makes it more mobile and problematic if contaminated surface water is used as a drinking water source. Consequently, there is a significantly increasing trend of PFBS in the environment and in people worldwide. Currently, there are no restrictions on the production and use of PFBS which is assumed to be less toxic than PFOS, and there is a significant knowledge gap regarding the level of human exposure and public health impact of PFBS. It is imperative that the impact of exposure and subsequent toxicity of PFBS be assessed to better inform health policy and regulation of their use.

Humans are exposed to PFASs via various pathways, including drinking water, diet, outdoor air, indoor dust, and soil. Such exposure has been linked to a number of adverse health conditions including cancer and abnormal reproductive development (USEPA, 2014). Available data including our unpublished data suggest that widespread exposure to PFBS may adversely affect human health including reproductive health. Although a direct causal association between maternal exposure of PFBS and pregnancy-induced hypertension (PIH) has not yet been reported, the toxicity of PFBS as shown in previous studies correlates highly with the pathophysiology (abnormal placenta development) of PIH such as endocrine disrupting, differential toxicity in human placental trophoblast cells, immunotoxicity; and transcriptional effects. Our pilot epidemiology study showed a positive association between PFBS exposure and risk of PIH which is the leading cause of maternal and fetal morbidity and mortality. In addition, a recent study showed that exposure of pregnant mice to PFBS causes hypothyroxinemia and abnormal development of female offspring. Our pilot study took a step further and demonstrated that cord blood level of PFBS is associated with lower levels of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in both maternal and cord blood in our pregnant human cohort. Proper thyroid hormone levels are critical for fetal growth and the maintenance of healthy pregnancy. Thus, maternal exposure of PFSB could affect short- and long-term health of both mothers and babies. The proposed study is uniquely positioned to answer critical public health questions about how perinatal exposure of PFBS impacts maternal and fetal health conditions. This study is a critical step towards exposure reduction policies for improving public health. We aims to determine the maternal PFBS exposure and the maternal and fetal outcomes and the underlining mechanisms.