A National Study of the Associations between Hormonal Modulators in Hydraulic Fracturing Fluid Chemicals and Birth Outcomes in the United States of America: A County-Level Analysis.

BACKGROUND Risk of preterm birth (PTB) and low birth weight (LBW) due to hydraulic fracturing (HF) exposure is a growing concern. Regional studies have demonstrated links, but results are often contradictory among studies. OBJECTIVES This is the first US national study to our knowledge linking fracturing fluid ingredients to the human hormone pathways targeted-estrogen, testosterone, or other hormones (e.g., thyroid hormone)-to assess the effect of HF ingredients on rates of PTB and LBW. METHODS We constructed generalized linear regression models of the impact of HF well density and hormone targeting chemicals in HF fluids (2001-2018) on the county-level average period prevalence rates of PTB and LBW (2015-2018) with each outcome measured in separate models. Our data sources consisted of publicly available datasets, including the WellExplorer database, which uses data from FracFocus, the March of Dimes Peristats, the US Census Bureau, the US Department of Agriculture, and the Centers for Disease Control and Prevention. We conducted additional stratified analyses to address issues of confounding. We used stratification to address issues regarding outcomes in rural vs. urban communities by assessing whether our models achieved similar results in nonmetro counties, as well as farming and mining counties. We also stratified by the year of the HF data to include HF data that was closer to the time of the birth outcomes. We also added covariate adjustment to address other important factors linked to adverse birth outcomes, including the proportion of the population belonging to various racial and ethnic minority populations (each modeled as a separate variable); education (bachelor's degree and high school); use of fertilizers, herbicides, and insecticides, acres of agricultural land per square mile; poverty; insurance status; marital status; population per square mile; maternal care deserts; and drug deaths per 100,000 people. RESULTS We found that the density of HF wells in a county was significantly associated with both PTB and LBW rates (percentage of live births) in our fully adjusted models. We report the results from our more restrictive stratified analysis with a subset including only the 2014-2018 data, because this resulted in the most meaningful time frame for comparison. Across all models, the magnitude of effect was highest for wells with ingredients that include estrogen targeting chemicals (ETCs), testosterone targeting chemicals (TTCs) and other hormone targeting chemicals (OHTCs), and, finally, all wells grouped regardless of chemical type. For every unit increase in well density per square mile of wells that use chemicals that include an ETC, we observed a 3.789-higher PTB rate (95% CI: 1.83, 5.74) compared with counties with no ETC wells from 2014 to 2018 and likewise, we observed a 1.964-higher LBW rate (95% CI: 0.41, 3.52). Similarly, for every unit increase in well density per square mile of wells that use TTC, we observed a 3.192-higher PTB rate (95% CI: 1.62, 4.77) compared with counties with no TTC wells. Likewise, for LBW, we found a 1.619-higher LBW rate (95% CI: 0.37, 2.87). We also found that an increase in well density per square mile among wells that use chemicals that include an OHTC resulting in a 2.276-higher PTB rate (95% CI: 1.25, 3.30) compared with counties with no OHTC wells, and for LBW, we found a 1.244-higher LBW rate (95% CI: 0.43, 2.06). We also explored the role of HF well exposure in general (regardless of the chemicals used) and found that an increase in total well density (grouped regardless of hormonal targeting status of the chemicals used) resulted in a 1.228-higher PTB rate (95% CI: 0.66, 1.80) compared with counties with no wells, and for LBW, we found a 0.602-higher LBW rate (95% CI: 0.15, 1.05) compared with counties with no wells. We found similar results in our primary analysis that used all data without any exclusions and the statistical significance did not change. DISCUSSION Our findings reinforce previously identified regional associations between HF and PTB and LBW, but on a national scale. Our findings point to dysregulation of hormonal pathways underpinning HF exposure risk on birth outcomes, which warrants further exploration. Future research must consider the specific ingredients used in HF fluids to properly understand the differential effects of exposure. https://doi.org/10.1289/EHP12628.