Maternal exposure to brominated flame retardants and infant Apgar scores

Abstract

Brominated flame retardants (BFRs) and other persistent organic pollutants have been associated with adverse health outcomes in humans and may be particularly toxic to the developing fetus. We investigated the association between in utero polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB) exposures and infant Apgar scores in a cohort of Michigan residents exposed to PBB through contaminated food after an industrial accident. PBB and PCB concentrations were measured in serum at the time the women were enrolled in the cohort. PBB concentrations were also estimated at the time of conception for each pregnancy using a validated elimination model. Apgar scores, a universal measure of infant health at birth, measured at 1 and 5 minutes, were taken from birth certificates for 613 offspring born to 330 women. Maternal PCB concentrations at enrollment were not associated with below–median Apgar scores in this cohort. However, maternal PBB exposure was associated with a dose–related increase in the odds of a below–median Apgar score at 1 minute and 5 minutes. Among infants whose mothers had an estimated PBB at conception above the limit of detection of 1 part per billion, the odds ratio was 2.32 (95 % CI: 1.22– 4.40); for those with PBB ≥ 2.5 ppb the OR=2.62 (95% CI: 1.38-4.96; test for trend p< 0.01). Likewise, the odds of a below–median 5–minute Apgar increased with higher maternal PBB at conception. It remains critical that future studies examine possible relationships between in utero exposures to brominated compounds and adverse health outcomes.

Quantification of Polybrominated and Polychlorinated Biphenyls in Human Matrices by Isotope-Dilution Gas Chromatography–Tandem Mass Spectrometry

“…However, limited method performance or validation data was provided other than internal standard recoveries, LOD and duplicate sample agreement. Average percent recovery and standard deviation were reported for the PBB-153 surrogate, 13 C 12 PBDE-153, as 50 ± 18, and for the PBB-209 surrogate, 13 C 12 PBDE-209, as 33 ± 22. LOD for PBB-153 was extrapolated from the lowest detected lipid-adjusted concentration in samples and reported as 0.01 ng/g.…”

“…Two transitions were then selected for each native analyte for quantification and confirmation. Only one transition was selected for each labeled analyte, 13 C-PBB-153, 13 C-PCB-118, 13 C-PCB-138, 13 C-PCB-153, and 13 C-PBB-180. All transitions were monitored in a multi-segment analysis using multiple reaction monitoring (MRM) mode, with wide resolution for MS1 and unit resolution for MS2.…”

“…Water was generated using a Milli-Q Ultrapure water purification system (Millipore, Billerica, MA C-ring labeled standard at 40 µg/mL in nonane (99% purity) and a mixed PCB congener 13 C-ring labeled standard at 5 µg/mL in nonane (98% purity) were also purchased from Cambridge Isotope Laboratories.…”

“…Not only were a large proportion of the reported data below the LOD but this also precluded evaluation of individual congener associations, which may contribute differently to toxicity and to related health outcomes. Even with such limited exposure characterization, research with this population has demonstrated intergenerational transfer of PBBs (12) and exposure-related health effects including poorer neonatal health (13), adverse reproductive outcomes (14), menstrual irregularities (15), accelerated pubertal development among females (16), increased incidence of urogenital problems (17), slower growth among males (18) and risk of digestive cancer and lymphoma (19) as well as a non-statistically significant increased incidence of breast cancer (19,20).…”

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

“…Additionally, because PBB can pass through the placental barrier and is present in breast milk, children born to exposed women are also exposed [23]. This cohort has reported many endocrine-related and reproductive health concerns, such as thyroid disease, spontaneous abortions, earlier age of menarche, and genitourinary conditions in male offspring, as well as breast cancer, digestive cancer, and lymphomas [24][25][26][27][28][29][30][31][32][33]. In general, the people who were exposed in utero or in childhood were found to be particularly susceptible to endocrine-related conditions [34].…”