Preterm birth in relation to the bisphenol A replacement, bisphenol S, and other phenols and parabens

Abstract

Introduction: Preterm birth continues to be a significant public heath concern and is a leading cause of perinatal and infant mortality. Environmental exposures to phenols and parabens are suspected to potentially contribute to the pathology of preterm birth, yet limited human studies have characterized the extent to which these toxicants are associated with birth outcomes.

Methods: We examined the associations between phenols, parabens, and preterm birth, within pregnant women who were recruited early in gestation into the LIFECODES cohort at Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points in pregnancy and analyzed for phenols and parabens. We selected 130 cases of preterm birth (defined as delivery before 37 weeks gestation), and 350 random controls. We categorized preterm birth subtypes based on clinical presentation and identified 75 cases of spontaneous preterm birth (characterized by spontaneous preterm labor and/or preterm premature rupture of membranes), and 37 cases of placental preterm birth (characterized by preeclampsia and/or intrauterine growth restriction). We used multivariate logistic regression with visit specific and geometric averages of phenols and parabens to determine associations with preterm birth.

Results: We observed moderate variability in urinary phenol and paraben concentrations over pregnancy with intraclass correlation coefficients ranging between 0.45 and 0.68. Regression analyses indicated mostly null associations. We observed inverse associations, notably between 2,5-dichlorophenol and overall preterm birth (adjusted odds ratio [95% confidence interval, CI]: 0.79 [0.67 - 0.94]), and this relationship was consistent by study visit. Conversely, ethyl paraben was associated with increased risk for placental preterm birth (adjusted odds ratio [95% CI]: 1.47 [1.14 - 1.91]). Bisphenol-S detection at visit 4 was associated with overall preterm birth (adjusted odds ratio [95% CI]: 2.05 [1.09, 3.89]).

Conclusions: While the findings from this study largely indicate null associations, we observed some relationships between select phenols, parabens and preterm birth, which warrants further investigation of these toxicants and birth outcomes.

Keywords: Parabens; Phenols; Preterm birth and subtypes; Repeated measures.

Figure 1.

Odds ratios for overall preterm birth in relation to individual phenols and parabens. Logistic regression models are adjusted for specific gravity at each study visit, maternal age (continuous), maternal race (categorical), pre-pregnancy BMI (continuous), insurance provider (categorical), maternal education level (categorical). Abbreviations: 2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); benzophenone-3 (BP3); triclosan (TCS); bisphenol-S (BPS); triclocarban (TCB). *BPS and TCB are modeled as categorical variables (detected in any of the repeated samples vs. all non-detect)