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Per- and Polyfluoroalkyl Substance Exposure Among Pediatric Patients Undergoing Orchiopexy
Maya M. Eldin, MD, MPH, Evelyn James, MPH, Lily C. Wang, MD, PhD.
MaineHealth Maine Medical Center, Portland, ME, USA.
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with recognized endocrine-disrupting properties. While PFAS exposure has been associated with adverse reproductive and developmental outcomes, its relationship with pediatric genitourinary conditions remains poorly understood. Testicular descent is partially hormonally mediated through pathways involving insulin-like factor 3 (INSL3), G protein-coupled receptor signaling, and androgen-dependent transinguinal descent. We evaluated whether PFAS exposure differed among pediatric patients with cryptorchidism undergoing orchiopexy compared to male controls.
METHODS: A retrospective case-control study was performed using pediatric patients ages 0-5 years evaluated between 2021 and 2026 within a large clinical database. Patients with cryptorchidism undergoing orchiopexy were identified using CPT codes. Controls consisted of male patients who did not undergo orchiopexy. ZIP code-level PFAS well water data were linked to patients using publicly available environmental monitoring datasets. For patients without directly matched PFAS data, exposure values were imputed using the nearest ZIP code with available PFAS measurements. PFAS exposure distributions between groups were compared using Kolmogorov-Smirnov (KS) testing. Threshold analysis was performed using a PFAS cutoff of 4 ng/L, which reflects the current EPA drinking water standard for select PFAS compounds.
RESULTS: A total of 215 orchiopexy patients and 27,766 male controls were included. Mean PFAS exposure was higher among orchiopexy patients compared to controls (7.90 vs 7.12 ng/L). KS testing demonstrated a difference in PFAS exposure distributions between groups (p=0.050). Threshold analysis demonstrated that 33.5% of orchiopexy patients exceeded the 4 ng/L exposure threshold compared to 24.3% of male controls (OR 1.57, p=0.002).
CONCLUSIONS: Pediatric patients with cryptorchidism undergoing orchiopexy demonstrated a higher prevalence of PFAS exposure above current EPA drinking water thresholds compared to male controls. These findings support a potential association between PFAS exposure and cryptorchidism-related surgical intervention. Given the multifactorial and hormonally mediated nature of testicular descent, PFAS exposure may represent one environmental contributor to abnormal testicular development. Limitations include inability to distinguish congenital cryptorchidism from ascending testes. Future studies evaluating cryptorchidism severity and testicular position are warranted.
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