Associations of prenatal concentrations of environmental phthalates and phenols with preeclampsia

Endocrine-disrupting chemicals (EDCs) like phthalates and phenols are ubiquitous in consumer products, raising concerns about fetal development and pregnancy complications such as hypertensive disorders of pregnancy (HDP). While usage of some EDCs is declining, substitutes with limited safety data are increasing. Prior research suggests a potential link between EDCs and HDP, but findings remain inconsistent. The objective of our study was to investigate the association between prenatal concentrations of phthalates, including replacements, and phenols and the risk of preeclampsia and gestational hypertension.

We analyzed individual-level pooled data from 4050 singleton pregnant individuals in the Environmental Influences on Child Health Outcomes consortium. A total of 7836 urine samples, collected at least once during pregnancy, were analyzed for 13 phthalate metabolites and 11 phenols. The outcomes were preeclampsia and gestational hypertension. Generalized estimating equations models with Poisson distribution and robust variance, and quantile-based g-computation fit with four quantiles, were used to estimate relative risks (RR) with 95% confidence intervals (95%CI).

Significant associations with preeclampsia were found for a 1-IQR increase in urinary concentrations of specific phthalates and phenols, including di-2-ethylhexyl phthalate (DEHP) (aRR, 1.34 [95% CI, 1.17-1.54]), Di-n-octyl phthalate (DOP) (aRR, 1.22 [95% CI, 1.03-1.44]), bisphenol A (aRR, 1.20 [95% CI, 1.03-1.39]), bisphenols (aRR, 1.22 [95% CI, 1.03-1.45]), parabens (aRR, 1.52 [95% CI, 1.12-2.06]), and mixture of plastic additives and plasticizers (aRR, 1.40 [95% CI, 1.03-1.92]). No significant associations were observed with phthalate replacements, including di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di(2-ethylhexyl) terephthalate (DEHTP). Interaction studies showed stronger associations in male fetuses. No significant associations were identified of any phthalate or phenol concentrations with gestational hypertension.

Results from this large US study raise the possibility that certain phthalate and phenol concentrations during pregnancy may be potentially modifiable risk factors for preeclampsia.