Mixtures of phthalates and phthalate replacements in relation to size-for-gestational age in the LIFECODES Fetal Growth Study

Abstract

BACKGROUND AND AIM: Phthalate exposure has been previously associated with reductions in fetal growth, including small-for-gestational age (SGA) births. Little is known about how phthalate replacements may be associated with adverse growth outcomes, including changes at both the small and large ends of the growth spectrum. Thus, we estimated joint associations between phthalates and their replacements with size-for-gestational age, including both SGA and large-for-gestational age (LGA) births. METHODS: Using the LIFECODES Fetal Growth Study, a case-cohort of 249 SGA, 411 appropriate-for-gestational age (AGA), and 241 LGA births, we measured concentrations of metabolites for 13 phthalates and 4 phthalate replacements at three timepoints during pregnancy. We used quantile g-computation as a multipollutant approach to estimate the joint association between phthalates or phthalate replacements and the odds ratios (OR) (95% confidence intervals [CI]) of an SGA or LGA birth. RESULTS: Of the metabolites analyzed, 12 phthalate and 2 phthalate replacements were detected frequently (> 70% of participants). The highest correlations were observed within chemical classes. Phthalate replacement metabolites were negatively correlated with phthalate metabolites. A simultaneous one-quartile increase in the concentrations of all phthalate replacement metabolites was associated with higher odds of an SGA birth (OR: 1.33, 95% CI: 1.13, 1.57) and inverse, though null, associations were observed for phthalate metabolites (OR: 0.82, 95% CI: 0.64, 1.07). Associations with LGA births were generally inverse or null. Single-pollutant models were consistent with our mixtures results. For example, an interquartile range-increase in concentrations of the phthalate replacement metabolite mono-2-ethyl 5-carboxypentyl terephthalate (OR: 1.64, 95% CI: 1.25, 2.15) was associated with higher odds of an SGA birth. CONCLUSIONS: Phthalate replacements were associated with higher odds of an SGA birth. Given the increasing prevalence of exposure to phthalate replacements, further research should continue to examine their health impacts. KEYWORDS: phthalates, phthalate replacements, fetal growth, mixtures