Associations of Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Uterine Fibroid Changes across Pregnancy: NICHD Fetal Growth Studies - Singletons Cohort

Abstract

Background: Fibroids (hormonally responsive benign tumors) often undergo volume changes in pregnancy. Because per- and polyfluoroalkyl substances (PFAS) disrupt hormonal signaling, they might affect fibroid growth. We assessed associations between PFAS and fibroid changes in pregnancy.

Methods: We analyzed seven PFAS, including perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), in plasma collected at 10-13 wk gestation from 2,621 women in the NICHD Fetal Growth Studies - Singletons cohort (2009-2013). Sonographers recorded fibroid number and volume of the three largest fibroids during up to six timed ultrasounds. Generalized linear models assessed associations of baseline ${\log }_2-\text{transformed}$ PFAS and fibroid number, volume, and presence, and weighted quantile sum regression evaluated the PFAS mixture. Generalized linear mixed models with random intercepts assessed associations of PFAS and longitudinal fibroid number and total volume. Volume analyses were stratified by total volume at first visualization [equivalent to a fibroid $<1\mathrm{cm}$ (small), $1\text{to}<3\mathrm{cm}$ (medium), or $\ge 3\mathrm{cm}$ (large) in diameter].

Results: Fibroid prevalence was 9.4% ($n=245$ women). PFAS were not associated with changes in fibroid number, but were associated with volume trajectory, depending on baseline volume. Among women with small volume, PFAS were associated with fibroid growth: Each doubling in PFHxS and PFOS concentrations was associated with 3.6% [95% confidence interval (CI): 0.2, 7.0 and 5.2% (95% CI: $-0.4$, 11.1)] greater weekly fibroid growth, respectively. Among women with medium volume, PFAS were associated with shrinking: Doublings in PFOS, PFDA, and PFUnDA concentrations were associated with 1.9% (95% CI: 0.4, 3.3), 1.2% (95% CI: 0.1, 2.4), and 1.6% (95% CI: 0.4, 2.8) greater weekly fibroid volume reduction, respectively.

Discussion: Certain PFAS were associated with fibroid growth among women with small fibroids and decreases among women with medium fibroids. PFAS were not associated with fibroid prevalence or number; therefore, PFAS may influence prevalent fibroids rather than initiating fibroid development. https://doi.org/10.1289/EHP11606.

Trial registration: ClinicalTrials.gov NCT00912132.

Figure 1.

Cross-sectional associations of first trimester (10–13 wk) PFAS concentrations and total fibroid volume ($n=161$ for all PFAS except NMeFOSAA; $n=132$ for NMeFOSAA). Effect estimates and 95% CIs represent percentage difference in total fibroid volume per doubling in PFAS concentration, based on parameter estimates from multivariable linear regression models adjusted for age, race/ethnicity, BMI, and education. Plotted values are listed in Supplemental Table S5. Note: BMI, body mass index; CI, confidence interval; NMeFOSAA, N-methylperfluoro-1-octane-sulfonamidoacetic acid; PFAS, per- and polyfluoroalkyl substances; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexanesulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctanesulfonic acid; PFUnDA, perfluoroundecanoic acid.

Figure 2.

Longitudinal associations of first trimester (10–13 wk) PFAS concentrations and change in total fibroid volume across pregnancy [$n=45$ (small volume), $n=111$ (medium volume), $n=89$ (large volume) for all PFAS except NMeFOSAA; $n=40$ (small volume), $n=97$ (medium volume), $n=67$ (large volume) for NMeFOSAA]. Effect estimates and 95% CIs are weekly percentage change in total fibroid volume per doubling in PFAS concentration, based on parameter estimates from multivariable generalized linear mixed models adjusted for age, race/ethnicity, BMI, and education. Plotted values are listed in Supplemental Table S8. Note: BMI, body mass index; COI, confidence interval; NMeFOSAA, N-methylperfluoro-1-octane-sulfonamidoacetic acid; PFAS, per- and polyfluoroalkyl substances.