Associations between brominated and organophosphate flame retardant levels and inflammatory biomarkers in maternal blood, cord blood, and placental tissue at mid-gestation.

OBJECTIVE

Prenatal exposures to flame retardants (FRs), including legacy polybrominated diphenyl ethers (PBDEs) and alternative organophosphate FRs (OPFRs), are associated with adverse pregnancy outcomes. In animal and cell models, inflammation has been proposed as a potential pathway of FR-toxicity; however, data in humans is limited. In this study, we assessed whether levels of FRs are associated with diverse inflammatory biomarkers, reflecting potential mediating pathways. We leveraged mid-gestation maternal and fetal biospecimens, a timepoint that is often difficult to study due to ethical challenges.

MATERIAL AND

METHODS

Participants in this study included a demographically diverse group of pregnant women undergoing elective mid-pregnancy terminations and for whom measurements of maternal OPFRs and PBDEs and maternal and fetal inflammation biomarkers were available (N = 65). Four PBDEs (BDE-47, BDE-99, BDE-100, BDE-153) and four OPFRs (BCEP, BCIPP, BDCIPP, DPHP) were quantified via mass spectrometry in mid-gestation maternal serum and urine samples, respectively. We measured 20 unique cytokines in matched maternal serum, cord blood, and placental tissue. We used quantile g-computation to assess mixture effects and linear regression to assess associations between individual FRs and cytokines. All models were adjusted for gestational age at time of sample collection, maternal age, education, and insurance.

RESULTS

A one-quartile increase in the mixture of PBDEs alone was positively associated with most maternal inflammatory mediators, including CCL-17 (Ѱ = 0.22, 95 % CI = 0.02, 0.42) and CCL-2 (Ѱ = 0.21, 95 % CI = 0.06, 0.37). Additionally, a one-quartile increase in the combined mixture of PBDEs and OPFRs was associated with increases in maternal serum levels of CCL-2, CCL-3, CC-17, and CCL-22. In contrast, BDE-47 and BDE-100 were individually associated with reductions in placental CCL-2 (β = -0.59, 95 % CI = -1.08, -0.1; β = -0.46, 95 % CI = -0.84, -0.07, respectively). No significant associations between levels of FRs in cord blood and cytokines were observed.

CONCLUSION

Prenatal exposure to FRs, particularly PBDEs, was significantly associated with differences in biomarkers of inflammation in maternal serum during mid-pregnancy.