Associations of pregnancy per- and polyfluoroalkyl substance concentrations and fibroid changes across pregnancy: NICHD Fetal Growth Studies - Singletons cohort

Abstract

BACKGROUND AND AIM: Uterine fibroids are common, hormonally responsive benign tumors. Because endocrine disrupting chemicals mimic hormones, they might affect fibroid growth. We tested associations of per- and polyfluoroalkyl substances (PFAS) and fibroid changes in pregnancy. METHODS: We quantified 11 PFAS, including perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanoic acid (PFOA) in first trimester blood from 2221 women. Sonographers recorded fibroid number and volume of the 3 largest fibroids in 1-6 ultrasounds at weeks 10-41. We used generalized linear mixed models with random intercepts and assessed associations of PFAS (quartiles) and changes in fibroid visualization (yes/no), number, and total volume by testing the PFAS*gestational age interaction, adjusted for race/ethnicity, body mass index, and age. Volume analyses were stratified by baseline total volume (equivalent to a 1cm (small), 1-3cm (medium), or 3cm (large) diameter fibroid). RESULTS:Visualized fibroid prevalence was 9.2% (n=204 women, 95% with ≥2 ultrasounds). PFAS were not associated with changes in fibroid number or visualization. Multiple PFAS were associated with volume changes. For example, among women with medium fibroids, PFDA and PFOA were inversely associated with volume growth. For PFDA, compared to Q1, fibroids in Q2 grew 4.7% (95%CI: 0.9, 8.4) less, Q3 grew 8.1% (95%CI: 4.2, 11.9) less, and Q4 grew 3.4% (95%CI: -0.1, 6.9) less per week; for PFOA, compared to Q1, fibroids in Q2 grew 0.4% (95%CI: -3.8, 4.8) more, Q3 grew 6.0% (95%CI: 2.2, 9.8) less, and Q4 grew 4.0% (95%CI: -0.0, 7.8) less per week. Among women with large fibroids, PFNA was positively associated with growth: compared to Q1, fibroids in Q2 shrank 4.7% (95%CI: 1.5, 7.9) less, Q3 shrank 4.6% (95%CI: 1.4, 8.0) less, and Q4 shrank 3.6% (95%CI: 0.9, 6.4) less per week. CONCLUSIONS:Certain PFAS were associated with changes in fibroid volume during pregnancy, varying by fibroid size. KEYWORDS: PFAS, Pregnancy outcomes