Dioxin-like compounds in paired maternal serum and breast milk under long sampling intervals.

Serum and breast milk are both important biological samples to evaluate body burden of dioxin-like compounds which include polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs). We collected maternal serum at early pregnancy, and breast milk at 3-8 weeks after delivery from 55 mothers living in Beijing, China, and measured 29 dioxin-like compounds in these samples. The sampling intervals in this study were extended up to 10 months to analyze differences of contents between serum and breast milk under long sampling intervals. The results showed that mean TEq level of PCDD/Fs in serum (9.8 pg TEq g-1 lipid) was 1.7 times higher than that in milk (4.5 pg TEq g-1 lipid), while the TEq concentrations of dl-PCBs in serum (1.2 pg TEq g-1 lipid) was significantly lower than that in milk (2.0 pg TEq g-1 lipid). There were only two congeners, OCDD (r = 0.32) and PCB105 (r = 0.33), the correlations of which between serum and milk were significant. The differences in distributions of congeners in serum and milk might be influenced by number of chlorine substituents and structures of congeners. In addition, maternal age and BMI were positively and negatively correlated with mass concentrations of dioxin-like compounds in milk and serum respectively. These results suggest that, compared with serum, it is limited to use breast milk to assess long-term exposure for the wider population.

Relative Effect Potency Estimates for Dioxin-Like Compounds in Pregnant Women with Gestational Diabetes Mellitus and Blood Glucose Outcomes Based on a Nested Case-control Study.

To improve the applicability of the toxic equivalents principle for human health risk assessment, systemic relative effect potencies (REPs) for dioxin-like compounds (DLCs) deriving from human in vivo data are required. A prospective nested case-control study was performed to determine REPs from the human serum concentration of DLCs using gestational diabetes mellitus (GDM) and fasting blood glucose (FBG) as the end points of concern. Serum concentration of 29 DLCs from 77 cases and 154 controls were measured. Logistic and linear regression were used to estimate the effects of individual congeners on GDM and FBG, respectively. The REPs based on GDM and FBG were calculated from the ratios of regression coefficients, ßi (DLCs)/ßTCDD. Two sets of consistent human serum-based REPs, that is, GDM-REP and FBG-REP, were established and largely agree with REPs from other human studies. These human-serum REPs show much smaller variation compared to the 4 to 5 orders of magnitude span in REPs database for the present WHO-TEF determination. Moreover, the established REPs fitted well with WHO-TEFs, especially for polychlorinated dibenzo- p-dioxins, furans. These REPs reflecting real human exposure scenarios exhibited validity and could be used to improve health risk assessment of human body burden of DLCs.

Structure-based investigation on the association between perfluoroalkyl acids exposure and both gestational diabetes mellitus and glucose homeostasis in pregnant women.

BACKGROUND: Biomonitoring studies have shown the presence of structurally diverse perfluoroalkyl acids (PFAAs) in humans but only a few studies are available regarding the differential structural effects of PFAAs on human health. OBJECTIVE: The specific association between different structural PFAAs and both gestational diabetes mellitus (GDM) and glucose homeostasis in pregnant women was investigated. METHODS: A prospective nested case-control study including 439 women was conducted during 2013-2015 in Beijing, China. First trimester maternal serum was collected and analyzed for 25 diverse PFAAs with varying carbon chain lengths, linear/branched isomers and carboxylate or sulfonate functional groups. The analyzed PFAAs were grouped into different exposure variables depending on structure characteristics. GDM cases were diagnosed at 24-28 weeks of gestation and individually matched in a 1:2 ratio to controls. Conditional logistic and linear regression was used to evaluate the association between structurally grouped PFAAs and both GDM risk and glucose homeostasis parameters. RESULTS: Among the 25 PFAAs, 12 perfluoroalkyl carboxylates (PFCAs) and 8 perfluoroalkyl sulfonates (PFSAs) were detected in >55.0% of samples and were respectively grouped into different structural groups. The structural-based effect was observed for PFCAs, where short-chain (C4-C7) PFCAs continuous level was significantly associated with GDM with an estimated odds ratio (OR) of 1.99 (95% CI: 1.29, 3.09), and the multivariable-adjusted ORs (95% CI) of GDM for increasing tertiles of short-chain PFCAs were 1.00 (ref.), 1.82 (0.80, 4.16) and 3.01 (1.31, 6.94), P trend = 0.011. Additionally, increased concentration of short-chain PFCAs was significantly associated with higher postprandial glucose levels (P < 0.05). Non-significant association was observed between structure grouped PFSAs and GDM as well as glucose homeostasis. CONCLUSION: This investigation suggests a structure-specific association between short-chain PFCAs exposure and both GDM risk and impaired glucose homeostasis in pregnant women. These findings warrant further investigation with larger samples and a wide range of short-chain PFCAs exposure.

A nested case-control study of the association between exposure to polybrominated diphenyl ethers and the risk of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is rapidly increasing worldwide. Exposure to endocrine-disrupting chemicals such as polybrominated diphenyl ethers (PBDEs) is thought to be a contributor to GDM, independent of diet and physical activity. OBJECTIVE: The prospective association between PBDEs body burden in early pregnancy and GDM risk was investigated. METHODS: A nested case-control study of 439 pregnant women was conducted between 2013 and 2015 in Beijing, China. Seven predominant PBDE congeners were measured in first trimester maternal serum by gas chromatography-high resolution mass spectrometry. Pregnant women were screened for GDM at 24-28 weeks of gestation using the oral glucose tolerance test. GDM was defined based on the diagnostic criteria set by China Ministry of Health. Conditional logistic and linear regression were used to estimate the association between PBDEs exposure and GDM risk, and PBDEs exposure and glucose level, respectively. RESULTS: A total of 77 (17.5%) women developed GDM in this study. Median concentrations of PBDEs were higher in women with GDM. Analyses parameterizing PBDE concentrations as continuous variables suggested significant associations between BDE-153, -154, -183 and GDM risk with an estimated odds ratio of 4.04 (95%CI: 1.92, 8.52), 1.88 (95%CI: 1.15, 3.09) and 1.91 (95%CI: 1.31, 2.08), respectively. In the quartile analyses, a significant increase in the odds ratio of GDM was associated with the highest levels of BDE-153 (OR = 3.42 95%CI: 1.49, 7.89) and BDE-183 (OR = 3.70, 95%CI: 1.58, 8.65), whereas, BDE-154 demonstrated an inverted U-shaped association with GDM. In addition, BDE-153 and -154 were significantly positively associated with fasting glucose, and both 1 h and 2 h glucose level (p < 0.05). CONCLUSIONS: These results suggest that exposure to PBDEs disturbs maternal glucose homeostasis and increases the risk of GDM. These findings should be replicated in future studies with a larger population and wider range of exposure.

Non-dioxin-like polychlorinated biphenyls in early pregnancy and risk of gestational diabetes mellitus.

Several studies support a plausible association of human exposure to polychlorinated biphenyls (PCBs) with type 2 diabetes mellitus. However, little is known about the potential link between circulating PCBs levels in early pregnancy and development of gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to determine the association of PCB exposure in early pregnancy with GDM risk. Concentrations of selected so-called 'indicator PCBs' were determined in sera of women in the first trimester of pregnancy via gas chromatography - high resolution mass spectrometry. Pregnant women were screened for GDM at 24-28 weeks of gestation using the oral glucose test (OGTT). GDM was defined based on the diagnostic criteria set by China Ministry of Health. Conditional logistic and linear regression models were employed to evaluate the association of PCB exposure with GDM risk and OGTT values, respectively. The odds ratios (OR) of PCB-28, PCB-52, and PCB-101 for GDM were 1.86 (95% CI: 1.05-3.27), 1.90 (95% CI: 1.28-2.82) and 1.85 (95% CI: 1.22-2.82), respectively. No statistical association was evident for other PCBs. However, after adjusting for confounders including some PCB congeners, only PCB-52 remained significantly associated with GDM with OR of 1.97 (95% CI: 1.27-3.07). Moreover, PCB-52 was positively associated with all blood glucose values of OGTT (p < 0.05). Our findings collectively suggest that serum levels of specific non-dioxin-like PCBs in early pregnancy disturb the glucose metabolism and increase the risk of GDM.