Table 4.
Epidemiologic studies of gestational diabetes mellitus (GDM) and chemical exposures in pregnant women (24)
| Persistent Organic Pollutants and Pesticides (12 Studies) | |||||||
| [89] | Prospective Cohort. | N=258, 28 GDM, 27 PIH. | 2005–2009. | Participation in Longitudinal Investigation of Fertility and the Environment Study (LIFE) study in 16 counties of Michigan and Texas, USA. | Measured maternal serum levels of 6 OCPs: HCB, β-HCH, p,p′-DDE, p,p′-DDT, oxychlordane, and trans-nonachlor; and 7 PBDE congeners: 28, 47, 85, 99, 100, 153, 154; soon before pregnancy (with detectable levels in >80% of subjects). | GDM, PIH. |
OCPs Ln HCB and GDM: Adjusted OR=0.97 (95% CI: 0.60–1.57) per SD increase in exposure. Ln β-HCH and GDM: Adjusted OR=0.34 (95% CI: 0.07–1.67) per SD increase in exposure. Ln oxychlordane and GDM: Adjusted OR=1.26 (95% CI: 0.76–2.08) per SD increase in exposure. Adjusted OR for oxychlordane was similar to that of p,p′-DDE, p,p′-DDT, and trans-Nonachlor, with adjusted OR ranging between 0.94–1.1 and 95% CI that crossed 1.0. PBDE congeners Ln PBDE-153 and GDM: Adjusted OR=1.79, (95% CI: 1.18–2.74) per SD increase in exposure. Ln PBDE-100 and GDM: Adjusted OR=2.22 (95% CI: 0.96–5.17) per SD increase in exposure. Ln PBDE-154 and GDM: Adjusted OR=1.04 (95% CI: 0.34–3.17) per SD increase in exposure. Ln PBDE-47 and GDM: Adjusted OR=0.32 (95% CI: 0.10–1.01) per SD increase in exposure. Adjusted OR for PBDE-28, 85, 99 was similar to PBDE-47, ranging between 0.44 and 0.71, with 95% confidence intervals that crossed 1.0. |
| [124] | Case-control. | N=140, 70 GDM. | 2013–2015. | Prenatal care patients at one of three hospitals in Tehran, Iran. | Measured maternal serum levels of 8 PBDE congeners: 28, 47, 99, 100, 153, 154, 183, and 209; and 10 PCB congeners: 28, 52, 74, 99, 101, 118, 138, 153, 180, and 187; once in 3rd trimester. |
GDM. |
Total POPs (sum of total PCBs and PBDEs) and GDM: Adjusted OR=1.61 (95% CI: 1.31–1.97, p-value <0.0001). Total PCBs and GDM: Adjusted OR=1.75 (95% CI: 1.35–2.27, p-value <0.0001). Total PBDEs and GDM: Adjusted OR=2.21 (95% CI: 1.48–3.30, p-value <0.0001). Individual PCB congeners Ln PCB 28 and GDM: Adjusted OR=0.30 (95% CI: 0.14–0.66, p-value=0.003). Ln PCB 187 and GDM: Adjusted OR=1.85 (95% CI: 1.16–2.94, p-value=0.01); and Ln PCB 118 and GDM: Adjusted OR=8.61 (95% CI: 2.80–26.48, p-value <0.0001). Ln PCB-153 and GDM: Adjusted OR=2.41 (95% CI: 1.21–4.81, p-value=0.01) Individual PBDE congeners Ln PBDE 99 and GDM: Adjusted OR=2.14 (95% CI: 1.99–3.83, p-value=0.01). Ln PBDE 28 and GDM: Adjusted OR=2.73 (95% CI: 1.22–6.11, p-value=0.02). Ln BDE-153 and GDM: Adjusted OR=1.81 (95% CI: 1.00–3.26, p-value=0.05). |
| [130] | Nested Case-control. | N=231, 77 GDM. | 2013–2015. | Prenatal care patients at Xicheng Maternal & Child Health Hospital in Beijing, China. | Measured maternal serum levels of 7 PBDE congeners: BDE-28, 47, 99, 100, 153, 154, 183; in the 1st trimester. | GDM. |
Single PBDE Model (Continuous) Ln BDE-28 and GDM: Adjusted OR=1.30 (95: CI: 0.89–1.91). Similar result for BDE-99. Ln BDE-47 and GDM: Adjusted OR=1.67 (95: CI: 1.00–2.77). Similar results for BDE-100, 154, and 183. Ln BDE-153 and GDM: Adjusted OR=4.04 (95: CI: 1.92–8.52). Single PBDE Model (Categorical) Ln BDE-28 and GDM: Adjusted OR=1.39 (95: CI: 0.59–3.28), 2.02 (95% CI: 0.86–4.70), 2.39 (95% CI: 1.03–5.57) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.05). Ln BDE-47 and GDM: Adjusted OR=1.28 (95% CI: 0.55, 2.98), 1.52 (95% CI: 0.66, 3.49), 2.01 (95% CI: 0.88, 4.60) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.09). Ln BDE-99 and GDM: Adjusted OR=1.29 (95% CI: 0.56, 3.00), 1.67 (95% CI: 0.73, 3.81), 2.01 (95% CI: 0.88, 4.58) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.08). Ln BDE-100 and GDM: Adjusted OR=0.97 (95% CI: 0.40, 2.35), 2.06 (95% CI: 0.90, 4.68), 2.04 (95% CI: 0.89, 4.70) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.03). Ln BDE-153 and GDM: Adjusted OR=1.43 (95% CI: 0.60–3.37), 1.36 (95% CI: 0.57–3.25), and 3.42 (95% CI: 1.49–7.89) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.01). Ln BDE-154 and GDM: Adjusted OR=1.37 (95% CI: 0.58–3.24), 2.67 (95% CI: 1.17–6.12), and 1.70 (95% CI: 0.73–3.99) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.18). Ln BDE-183 and GDM: Adjusted OR=1.30 (95% CI: 0.53–3.22), 2.15 (95% CI: 0.89–5.16), and 3.70 (95% CI: 1.58–8.65) for women in the 2nd, 3rd, and 4th exposure quartiles compared to the lowest exposure quartile (p-trend <0.01). Ln Total BDE and GDM: Adjusted OR=1.00 (95% CI: 0.43–2.34), 1.48 (95% CI: 0.65–3.37), and 2.23 (95% CI: 1.04–5.00) for women in the 2nd, 3rd, and 4th PBDE exposure groups compared to the lowest exposure quartile (p-trend=0.03). Multiple PBDE congener model Ln BDE-28 and GDM: Adjusted OR=1.09 (95: CI: 0.71–1.67). Similar result for BDE-100 and BDE-154. Ln BDE-47 and GDM: Adjusted OR=1.33 (95: CI: 0.55–3.21). Ln BDE-99 and GDM: Adjusted OR=0.71 (95: CI: 0.18–2.75). Ln BDE-153 and GDM: Adjusted OR=2.76 (95: CI: 1.07–7.11). Ln BDE-183 and GDM: Adjusted OR=1.56 (95: CI: 1.02–2.40). Tests for the trends in BDE-28, −100, −153, −183 and summed PBDE exposure were all statistically significant (p <0.05), non-monotonic patterns also observed for BDE-100 and −183. |
| [125] | Prospective Cohort. | N=939, 68 GDM. | 2007–2008. | Participation in Rhea Study at prefecture of Heraklion, Crete, Greece. | Measured maternal serum levels of 2 OCPs (HCB and DDE) and 6 PCB congeners: non-dioxin-like (153, 138, 170 180) and dioxin like (118 and 156); once in 1st trimester. | GDM. |
OCPs and GDM HCB and GDM: Adjusted OR=1.62 (95% CI: 0.67–3.95) and 1.21 (95% CI: 0.45–3.20) for women in medium and high tertiles of HCB exposure compared to women in the lowest exposure tertile. DDE and GDM: Adjusted OR=0.83 (95% CI: 0.38–1.82) and 0.65 (95% CI: 0.28–1.47) for women in the medium and high tertiles of exposure, compared to women in the lowest exposure tertile. Total PCB metrics and GDM Total PCBs and GDM: Adjusted OR=3.90 (95% CI: 1.37–11.06) and 3.60 (95% CI: 1.14–11.39) for women in the medium and high tertiles of PCB exposure, respectively, compared to women in the lowest tertile of PCB exposure. Dioxin-like PCBs and GDM: Adjusted OR=5.63 (95% CI: 1.81–17.51) and 4.71 (95% CI: 1.38–16.01) for women in the medium and high exposure tertiles, respectively, compared to women in the lowest exposure tertile. Non-dioxin-like PCBs and GDM: Adjusted OR=2.36 (95% CI: 0.89–6.23) and 2.26 (95% CI: 0.77–6.68) for women in the medium and high tertiles of non-dioxin-like PCB exposure groups, compared to women in the lowest tertile of PCB exposure group. |
| [126] | Nested Case-control. | N=231, 77 GDM. | 2013–2015. | Prenatal care patients at Xicheng Maternal and Child Care Hospital, Beijing, China. | Measured maternal serum levels of 6 non-dioxin-like PCB congeners: 28, 52, 101, 138, 153, and 180; in 1st trimester. | GDM, Glucose Homeostasis. |
PCB summary metrics Ln Low chlorinated PCBs (ΣPCB-28,−52,−101) and GDM: Unadjusted OR=2.28 (95% CI: 1.25–4.17). Dose response observed in cubic spline graphs. Ln High chlorinated PCBs (ΣPCB-138,−153 −180) and GDM: Unadjusted OR=1.45 (95% CI: 0.87–2.42). Ln Total ΣPCB (six congeners) and GDM: Unadjusted OR=4.70 (95% CI: 1.02–21.7). Individual PCB congeners Ln PCB-28 and GDM: Unadjusted OR=1.86 (95% CI: 1.05–3.27). Similar result for PCB-52 and PCB-101. Ln PCB-138 and GDM: Unadjusted OR=1.51 (95% CI: 0.90–2.53). Similar result for PCB-153 and PCB-180. PCB-52 and GDM: Adjusted OR=1.97 (95% CI: 1.27–3.07), with evidence of a dose response relationship. Note: PCB-52 was the only congener that remained significant in adjusted models and the only for which adjusted results were reported. Similar findings observed for PCB-52 and glucose homeostasis. |
| [134] | Prospective Cohort. | N=604, 49 GDM. | 1997–2000. | Delivery at National Hospital in Torshavn, Faroe Islands. | Measured maternal serum levels of 3 PCB congeners: 138, 153, 180; DDT/DDE; and 5 PFAS: PFOS, PFOA, PFHxS, PFDA, and PFNA; at 34 weeks gestation; and hair and cord blood levels of mercury at delivery. | GDM. |
Serum Ln ΣPCB and GDM: Adjusted OR=0.97 (95% CI: 0.71, 1.33) per doubling of exposure and. When modeled as three categories: Adjusted OR=1.08 (95% CI: 0.49, 2.39) and 1.26 (95% CI: 0.57–2.75). Serum Ln DDE and GDM: Adjusted OR=1.29 (95% CI: 0.94, 1.77) per doubling of exposure. Adjusted OR=1.17 (95% CI: 0.44–3.09) and 1.89 (95% CI: 0.75–4.76) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Serum Ln PFOS and GDM: Adjusted OR=0.86 (95% CI: 0.43–1.70) per doubling of exposure. Adjusted OR=0.85 (95% CI: 0.43–1.70) and 0.56 (95% CI: 0.26–1.19) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Serum Ln PFOA and GDM: Adjusted OR=0.79 (95% CI: 0.44–1.41) per doubling of exposure. Adjusted OR=1.01 (95% CI: 0.50–2.06) and 0.66 (95% CI: 0.30–1.48) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Serum Ln PFHxS and GDM: Adjusted OR=1.03 (95% CI: 0.80–1.33) per doubling of exposure. Adjusted OR=0.98 (95% CI: 0.47–2.05) and 1.00 (95% CI: 0.48–2.07) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Serum Ln PFDA and GDM: Adjusted OR=1.20 (95% CI: 0.73–1.96) per doubling of exposure. Adjusted OR=1.97 (95% CI: 0.94–4.12) and 1.02 (95% CI: 0.45–2.30) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Serum Ln PFNA and GDM: Adjusted OR=0.88 (95% CI: 0.53–1.47) per doubling of exposure. Adjusted OR=0.62 (95% CI: 0.30–1.30) and 0.65 (95% CI: 0.31–1.36) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Hair mercury and GDM: Adjusted OR=0.79 (95% CI: 0.62–0.99) per doubling of exposure. Adjusted OR=0.92 (95% CI: 0.44–1.90) and 0.73 (95% CI: 0.34–1.59) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. Cord blood mercury and GDM: Adjusted OR=0.87 (95% CI: 0.66–1.15) per doubling of exposure. Adjusted OR=1.08 (95% CI: 0.52–2.26) and 0.73 (95% CI: 0.33–1.62) for women in the 2nd and 3rd exposure group compared to women in the lowest exposure group. In the multiple pollutant adjusted structural equation models (SEMs), only the positive association between OC exposure (which included ΣPCB and DDT/DDE) and GDM remained significant (change in GDM probit per doubling of OC exposure = 0.45, 95% CI: 0.05–0.86). |
| [127] | Prospective Cohort. | N=1274, 48 GDM, 59 IGT. | 2008–2011. | Participation in Maternal-Infant Research on Environmental Chemicals (MIREC) study from 10 sites in six Canadian provinces, Canada. | Measured urine levels of 3 OP pesticide metabolites: diethyl-, dimethyl-, and dimethylthio-phosphate (DEP, DMP, and DMTP, respectively); plasma levels of 3 OCPs: p,p′-DDE, oxychlordane, and trans-nonachlor; 3 PFAS: PFOA, PFOS, and PFHxS; and 4 PCB congeners: 118, 138, 153, 180; once during 1st trimester (with detectable levels in >75% of subjects). | GDM, IGT. |
OP pesticide metabolites and GDM: Except for comparing the 3rd and the 4th to the lowest quartile of DMP exposure [adjusted OR=0.2 (95% CI: 0.1–0.7) and 0.3 (95% CI: 0.1–0.8) respectively], comparing the 4th to the lowest quartile of DMTP exposure [0.3 (95% CI: 0.1–0.9)], and comparing the 4th to the lowest quartile of dimethyl OP metabolites (DMP and DMTP) exposure [0.3 (95% CI: 0.1–0.8)], no statistically significant associations comparing higher exposure to the lowest exposure quartile were reported. Significant trend associations were found for DMP, DMTP, and DMP/DMTP OP metabolites. OP pesticide metabolites and IGT: Except for comparing the 3rd to the lowest quartile of DEP exposure [adjusted OR=0.2 (95% CI: 0.1–0.6)], no statistically significant associations comparing higher exposure to the lowest exposure quartile were reported. Significant trend association was found for DMP. OP pesticide metabolites and GDM/IGT: Except for comparing the 3rd to the lowest quartile of DEP exposure [adjusted OR=0.4 (95% CI: 0.2–0.9)], the 3rd and the 4th to the lowest quartile of DMP exposure [adjusted OR=0.2 (95% CI: 0.1–0.7) and 0.3 (95% CI: 0.1–0.8) respectively], the 4th to the lowest quartile of DMTP exposure [0.3 (95% CI: 0.1–0.9)], and the 3rd and 4th to the lowest quartile of dimethyl OP metabolites (DMP and DMTP) exposure [0.5 (95% CI: 0.3–0.9) and 0.5 (95% CI: 0.2–0.9)], no statistically significant associations comparing higher exposure to the lowest exposure quartile were reported. Significant trend associations were found for DMP, DMTP, and DMP/DMTP OP metabolites. OCPs and GDM: Adjusted ORs ranging from 0.5–1.4, with 95% CI that crossed 1.0]. OCPs and IGT: Adjusted ORs ranged from 0.6–1.0, with confidence intervals that crossed 1.0. OCPs and GDM/IGT: No significant associations were reported [adjusted OR ranging from 0.6 to 1.0, with confidence intervals that crossed 1.0]. PCBs and GDM: No significant associations reported between GDM and individual PCBs, sum of all PCBs, and sum of non-dioxin-like PCBs [adjusted OR ranging from 0.7 to 1.9, with confidence intervals that crossed 1.0]. PCBs and IGT: No significant associations were reported between GDM and individual PCBs, sum of all PCBs, and sum of non-dioxin-like PCBs [adjusted OR ranging from 0.4 to 0.9, with confidence intervals that crossed 1.0]. PCBs and GDM/IGT: No significant associations were reported between GDM and individual PCBs, sum of all PCBs, and sum of non-dioxin-like PCBs [adjusted OR ranging from 0.5 to 1.1, with confidence intervals that crossed 1.0]. PFAS and GDM: Adjusted ORs ranging from 0.6 to 1.6, with confidence intervals that crossed 1.0. PFAS and IGT: Except for comparing the 2nd to the lowest quartile of PFHxS exposure [adjusted OR=3.5 (95% CI: 1.4–8.9)], no statistically significant associations comparing higher exposure to the lowest exposure quartile were reported. PFAS and GDM/IGT: Except for comparing the 2nd to the lowest quartile of PFHxS exposure [adjusted OR=2.4 (95% CI: 1.3–4.4)], no statistically significant associations comparing higher exposure to the lowest exposure quartile were reported. |
| [129] | Prospective Cohort. | N=258, 28 GDM. | 2005–2007. | Participation in Longitudinal Investigation of Fertility and the Environment (LIFE) Study and residence in sixteen counties in Michigan and Texas, USA. | Measured maternal serum levels of PBB-153 and 36 PCBs: PCB 28, 44, 66, 74, 99, 101, 105, 110, 114, 118, 146, 157, 170, 177, 183, 197, 195, 196, 201, 206, and 209); once soon before pregnancy. | GDM. |
Individual congeners PCB 28 and GDM: Adjusted OR=0.90 (95% CI: 0.24–3.31). Results for PCB 44, 66, 74, 99, 101, 105, 110, 114, 118, 146, 157, 170, 177, 183, 197, 195, 196, 201, 206, and 209 were similar, with adjusted OR’s between 0.46–0.96 and confidence intervals that contained 1.0. PCB-101 and GDM: Adjusted OR=1.0 (95% CI: 0.69–1.47) PCB-170 and GDM: Adjusted OR=0.4 (95% CI: 0.18–0.88). Results for PCB 138, 153, 156, 167, 172, 180, and 194 were similar, with adjusted OR’s between 0.42–0.53 and confidence intervals that were less than 1.0. PBB-153 and GDM: Adjusted OR=0.68 (95% CI: 0.31–1.49). Congener sums Dioxin-like PCBs and GDM: Adjusted OR=0.65 (95% CI: 0.37–1.15). Non-dioxin-like PCBs and GDM: Adjusted OR=0.37 (95% CI: 0.13–1.04). |
| [133] | Retrospective Cohort. | N=11,273, 506 GDM. | 1993–1997. | Licensed pesticide applicators and spouses enrolled in Agricultural Health Study (AHS), Iowa and North Carolina, USA. | Modeled pesticide exposure from self-reported activity in 1 st trimester as four ordered categories: 1) No exposure; 2) Indirect exposure (planting, pruning, weeding, picking, harvesting); 3) Residential exposure (use in garden or home); and 4) Agricultural exposure (mixing, applying, repairing equipment). | GDM. |
Pesticides and GDM: Adjusted OR=0.9 (95% CI: 0.7–1.1), 1.0 (95% CI: 0.8–1.3), and 2.2 (95% CI: 1.5–3.3) for women in the 2nd (indirect), 3rd (residential), and 4th (agricultural) exposure groups compared to women in the 1st (non-exposed) group. Elevated GDM associated with ever-use of four herbicides (2,4,5-T; 2,4,5-TP; atrazine, and butylate), two OP insecticides (diazinon and phorate), and one carbamate insecticide (carbofuran) among women in the agricultural exposure group (specific values not reported). |
| [93] | Prospective Cohort. | N=779, 71 GDM. | 2004–2007. | Participation in prospective mother-child cohort study, Timoun, Guadeloupe. | Measured plasma levels of chlordecone in 3rd trimester (DDE and PCB-153 analyzed as potential confounders in a subset of samples). | GDM, PE, PIH. |
Log10 Chlordecone and GDM: Adjusted OR=0.7 (95% CI: 0.5–1.1). When modeled as quartiles: Adjusted OR=1.1 (95% CI: 0.6–2.2), 0.5 (95% CI: 0.2–1.1), and 0.7 (95% CI: 0.3–1.5) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to women in the lowest exposure quartile. |
| [132] | Prospective Cohort. | N=1240, 53 GDM, 137 IGT. | 2003–2008. | Participation in Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort, Spanish regions of Valencia, Sabadell, and Gipuzkoa, Spain. | Measured maternal plasma levels of 4 PFAS: PFOS, PFHxS, PFNA, and PFOA; once in 1st trimester. | GDM, IGT. |
Log10 PFOA and GDM: Adjusted OR=1.20 (0.62–2.30). Similar result when exposure modeled categorically and for Log10 PFOA and IGT. PFOA and total cholesterol: %Difference=1.26% (95% CI: 0.01%–2.54%) per log10-unit increase. Log10 PFOS and GDM: Adjusted OR=2.40 (0.93–6.18). When exposure was modeled as four categories: Adjusted OR=1.89 (0.77–4.64), 1.54 (0.61–3.87), and 2.07 (0.85–5.01). Log10 PFOS and IGT: Adjusted OR=1.99 (95% CI: 1.06–3.78). Adjusted OR=2.11 (1.13–3.94), 2.08 (1.12–3.86), and 2.22 (1.19–4.13). PFOS and triglyceride: %Difference=−5:86 (95% CI: −9:91%–1:63%) per log10-unit increase. Log10 PFHxS and GDM: Adjusted OR=1.58 (0.73–3.44). When exposure was modeled as four categories: Adjusted OR=1.25 (0.51–3.03), 1.81 (0.76–4.28), and 1.15 (0.42–3.12). Log10 PFHxS and IGT: 1.65 (0.99–2.76). Adjusted OR=1.51 (0.76–3.02), 1.99 (1.01–3.90), and 1.72 (0.85–3.49). Log10 PFNA and GDM: Adjusted OR=0.85 (0.40–1.80). OR=1.01 (0.62–2.23), 1.27 (0.59–2.73), and 0.70 (0.28–1.75). Similar result for Log10 PFNA and IGT. PFNA and triglyceride: %Difference=−4:75% (95% CI: −8:16%–−0.61%) per log10-unit increase. |
| [131] | Prospective Cohort. | N=272, 28 GDM. | 2005–2009. | Participation in Longitudinal Investigation of Fertility and the Environment (LIFE) Study in 16 counties of Michigan and Texas, USA. | Measured maternal serum levels of 7 PFAS: PFOA, PFOS, PFOSA, PFNA, PFDeA, Me-PFOSA-AcOH, Et-PFOSA-AcOH; soon before pregnancy. | GDM. |
Ln PFOA and GDM: Adjusted OR=1.85 (95% CI: 1.15–2.98) per SD increment. Ln PFOS and GDM: Adjusted OR=1.16 (95% CI: 0.77–1.76) per SD increment. Similar results for Ln PFOSA, Ln PFNA, Ln PFDeA, Ln Me-PFOSA-AcOH, and Ln Et-PFOSA-AcOH. |
| Non-persistent Chemicals (5 Studies) | |||||||
| [136] | Case-control. | N=94, 22 GDM. | 2009–2010. | Prenatal care patients at University of Oklahoma Medical Center Women’s and High Risk Pregnancy clinics, Oklahoma City, Oklahoma, USA. | Measured urine levels of total BPA (free BPA and conjugate) in banked samples at 27 weeks gestation. | GDM, Blood Glucose. | BPA and GDM: Adjusted OR=0.58 (95% CI: 0.18–1.19) and 0.37 (95% CI: 0.09–1.60) for women in the 2nd and 3rd tertiles of BPA exposure compared to women in the lowest exposure tertile. Note: There was no association between BPA and blood glucose levels, but the values were not reported. |
| [138] | Prospective Cohort. | N=1274, 48 GDM, 59 IGT. | 2008–2011. | Participation in Maternal-Infant Research on Environmental Chemicals (MIREC) study at 10 sites in six provinces, Canada. | Measured urine levels of total BPA and 11 phthalate metabolites: MEP, MnBP, MBzP, MCPP, DEHP metabolites; and blood levels of 4 metals: lead, cadmium, mercury, and arsenic; once in 1st trimester. | GDM, IGT. |
MEP: Adjusted OR (95% CI) GDM: Adjusted OR=0.7 (95% CI: 0.3–1.8), p-value=0.25; IGT: 1.5 (95% CI: 0.6–3.8), p-value=0.72; GDM or IGT: 1.0 (95% CI: 0.5–2.0), p-value=0.29. GDM: Adjusted OR=0.8 (0.3–2.1); IGT: 0.8 (0.3–2.4); GDM or IGT: 0.8 (0.4–1.7). GDM: Adjusted OR=0.5 (0.2–1.4), IGT: 1.0 (0.4–3.0), GDM or IGT: 0.7 (0.3–1.5). MBP: Adjusted OR (95% CI) GDM: 1.7 (0.6–4.4), IGT: 1.9 (0.7–5.2), GDM or IGT 1.8 (0.9–3.6) GDM: 1.0 (0.3–3.2), IGT: 1.7 (0.5–5.4), GDM or IGT 1.3 (0.6–3.0) GDM: 0.6 (0.1–2.2), IGT: 1.2 (0.3–4.6), GDM or IGT 0.8 (0.3–2.2) p-Value c GDM: 0.29, IGT: 0.95, GDM or IGT 0.51 MBzP: Adjusted OR (95% CI) GDM: 0.7 (0.2–2.2), IGT: 2.3 (0.8–7.2), GDM or IGT 1.3 (0.6–2.8) GDM: 1.5 (0.6–4.2), IGT: 2.9 (0.9–9.4), GDM or IGT 2.0 (0.9–4.4) GDM: 1.5 (0.5–4.7), IGT: 2.9 (0.8–10.4), GDM or IGT 2.0 (0.9–4.8) p-Value c GDM: 0.28, IGT: 0.13, GDM or IGT 0.07 MCPP: Adjusted OR (95% CI GDM: 1.2 (0.5–2.9), IGT: 1.8 (0.7–4.5), GDM or IGT 1.5 (0.7–2.8) GDM: 0.6 (0.2–1.8), IGT: 0.5 (0.1–1.8), GDM or IGT 0.6 (0.2–1.3) GDM: 0.6 (0.2–1.9), IGT: 1.6 (0.5–4.8), GDM or IGT 1.0 (0.4–2.3) p-Value c GDM: 0.27, IGT: 0.70, GDM or IGT 0.63 ΣDEHP: Adjusted OR (95% CI GDM: 1.0 (0.4–2.5), IGT: 1.1 (0.4–2.8), GDM or IGT 1.0 (0.5–2.0) GDM: 0.4 (0.1–1.5), IGT: 0.9 (0.3–2.7), GDM or IGT 0.6 (0.3–1.5) GDM: 0.9 (0.3–2.9), IGT: 1.0 (0.3–3.4), GDM or IGT 0.9 (0.4–2.3) p-Value c GDM: 0.72, IGT: 0.91 0.75 BPA: Adjusted OR (95% CI GDM: 1.8 (0.7–4.5), IGT: 1.2 (0.5–2.9), GDM or IGT 1.5 (0.8–2.9) GDM: 1.5 (0.5–4.5), IGT: 0.6 (0.2–1.7), GDM or IGT 0.9 (0.4–2.0) GDM: 1.1 (0.3–3.6), IGT: 1.3 (0.5–3.6), GDM or IGT 1.2 (0.5–2.7) p-Value c GDM: 0.99, IGT: 0.79, GDM or IGT 0.92 |
| [137] | Prospective Cohort. | N=1795,42 GDM, 43 IGT. | 2008–2011. | Participation in Maternal-Infant Research on Environmental Chemicals (MIREC) study at 10 sites in six provinces, Canada. | Measured urine levels of triclosan in 1st trimester. | GDM, IGT, Other complications. |
Ln Triclosan and GDM: Adjusted OR=1.7 (95% CI: 0.7–4.2), 0.9 (95% CI: 0.3–2.5), and 0.9 (95% CI: 0.4–2.5) for women in the 2nd, 3rd, and 4th exposure quartiles compared to women in the lowest exposure quartile (p-trend=0.54). Ln Triclosan and IGT: Adjusted OR=0.3 (95% CI: 0.1–1.0), 0.5 (95% CI: 0.2–1.3), and 0.7 (95% CI: 0.3–1.5) for women in the 2nd, 3rd, and 4th exposure quartiles compared to women in the lowest exposure quartile (p-trend=0.55). Ln Triclosan and GDM or IGT: Adjusted OR=0.8 (95% CI: 0.4–1.5), 0.7 (95% CI: 0.3–1.3), and 0.8 (95% CI: 0.4–1.5) for women in the 2nd, 3rd, and 4th exposure quartiles compared to women in the lowest exposure quartile (p-trend=0.40). |
| [135] | Retrospective Nested Case-control. | N=232, 47 GDM. | 2001–2009. | Male pregnancy and participation in Cambridge Baby Growth Study (CBGS), Rosie Maternity Unit, Cambridge, United Kingdom. | Measured maternal serum levels of 3 phenols: BPA, triclosan, and BP-3; and 6 phthalate metabolites: MEP, MiBP, MnBP, MEHP, MECPP, and MCiOP; once at 10–17 weeks gestation (detected in > 60% of samples). | GDM, Glucose Homeostasis. |
Ln BPA and Incident GDM: Adjusted OR=1.16 (95% CI: 0.48–2.78, p-value=0.74). When exposure was modeled in quartiles: Adjusted OR=2.58 (95% CI: 0.84–7.94), 1.04 (95% CI: 0.31–3.53), and 0.56 (95% CI: 0.14–2.28) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.07, p-trend=0.24). Ln Triclosan and GDM: Adjusted OR=0.54 (95% CI: 0.34–0.86, p-value=0.010). When exposure was modeled in quartiles: Adjusted OR=0.25 (95% CI: 0.07–0.86), 0.12 (95% CI: 0.03–0.55), and 0.35 (95% CI: 0.12–0.98) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.009, p-trend=0.022). BP-3 and Incident GDM: Adjusted OR=0.80 (95% CI: 0.44–1.44, p-value=0.45). Adjusted OR (95% CI: 95% CI), a Referent 1.09 (95% CI: 0.38–3.14), 1.40 (95% CI: 0.52–3.77), and 0.86 (95% CI: 0.29–2.51) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.83, p-trend=0.95). Ln MEP and Incident GDM: Adjusted OR=0.81 (95% CI: 0.39–1.70, p-value= 0.58). When exposure was modeled in quartiles: Adjusted OR=1.65 (95% CI: 0.60–4.56), 0.67 (95% CI: 0.21–2.07), and 1.19 (95% CI: 0.42–3.37) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.45,-trend=0.87). Ln MiBP and Incident GDM: Adjusted OR=1.48 (95% CI: 0.51–4.34, p-value=0.47). When exposure was modeled in quartiles: Adjusted OR=5.69 (95% CI: 1.56–20.73), 0.37 (95% CI: 0.06–2.26), and 4.89 (95% CI: 1.32–18.14) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (phet = 0.001, p-trend = 0.41).. Ln MnBP and Incident GDM: Adjusted OR=1.55 (95% CI: 0.45–5.33, p-value=0.49). When exposure was modeled in quartiles: Adjusted OR=1.17 (95% CI: 0.40–3.41), 0.43 (95% CI: 0.13–1.44), and 1.42 (95% CI: 0.52–3.88) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.26, p-trend=0.81). Ln MEHP and Incident GDM: Adjusted OR=0.93 (95% CI: 0.66–1.31, p-value=0.67). When exposure was modeled in quartiles: Adjusted OR=2.14 (95% CI: 0.72–6.35), 1.14 (95% CI: 0.42–3.09), and 1.03 (95% CI: 0.38–2.79) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.53, p-trend=0.77). Ln MECPP and Incident GDM: Adjusted OR=0.75 (95% CI: 0.27–2.06, p-value= 0.57). When exposure was modeled in quartiles: Adjusted OR=0.61 (95% CI: 0.20–1.81), 0.42 (95% CI: 0.13–1.36), and 1.19 (95% CI: 0.44–3.17) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.29, p-trend=0.78). Ln MCiOP and Incident GDM: Adjusted OR=1.12 (95% CI: 0.47–2.66, p-value= 0.81). When exposure was modeled in quartiles: Adjusted OR=1.54 (95% CI: 0.53–4.52), 1.18 (95% CI: 0.38–3.67), and 1.39 (95% CI: 0.47–4.14) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-het=0.87, p-trend=0.89). Note: Among women without GDM, first-trimester MEHP levels were positively associated with 120-min plasma glucose (adjusted β = 0.268 and 0.183, p-value = 0.0002 and 0.010, respectively) in mid-pregnancy. |
| [146]) | Retrospective Case-control. | N=81,205, 119 GDM (mani), 299 GDM (cosmet). | 1996–2009. | Licensed cosmetologists and manicurists in California, USA. | Modeled non-persistent chemicals in beauty products using California cosmetology license (hair and nail care services) and/or manicurist license during 1996–2006 as proxies for occupational exposure. | GDM, PE, Other complications. |
Compared to other working women Manicurist and GDM: Adjusted OR=1.19 (95% CI: 0.93–1.51). Restricted to Vietnamese manicurists: Adjusted OR=1.18 (95% CI: 0.47–2.97). Cosmetologist and GDM: Adjusted OR=1.14 (95% CI: 0.94–1.39). Restricted to Vietnamese cosmetologists: Adjusted OR=1.11 (95% CI: 0.43–2.86). Compared to the general population Manicurist and GDM: Adjusted OR=1.28 (95% CI: 1.10–1.50). Restricted to Vietnamese manicurists: Adjusted OR=1.59 (95% CI: 1.20–2.11). Cosmetologist and GDM: Adjusted OR=1.19 (95% CI: 1.07–1.33). Restricted to Vietnamese cosmetologists: Adjusted OR=1.49 (95% CI: 1.04–2.11). |
| Heavy Metals/Metalloids (7 Studies) | |||||||
| [139] | Cross-sectional. | N=532. | 2002–2008. | Participation in prospective birth cohort and residence near Tar Creek Superfund site, Ottawa County, Oklahoma, USA. | Measured maternal blood and hair levels of arsenic, once at delivery. | IGT. |
Arsenic and IGT (Blood): Adjusted OR=1.65 (95% CI: 1.52–1.79) per IQR increase in blood arsenic levels. When exposure was modeled in quartiles: Adjusted OR=1.02 (95% CI: 0.39–2.69), 2.65 (95% CI: 1.12–6.36), and 2.79 (95% CI: 1.13–6.87) for women in the 2nd, 3rd, and 4th arsenic exposure groups compared to the lowest exposure quartile (p-trend=0.008). Arsenic and IGT (Hair): Adjusted OR=2.32 (95% CI: 0.52–10.39) per IQR increase in hair arsenic levels. When exposure was modeled in quartiles: Adjusted OR=3.97 (95% CI: 0.62–25.37). 5.77 (95% CI: 0.98–33.88), and 4.20 (95% CI: 0.74–23.86) for women in the 2nd, 3rd, and 4th exposure quartiles compared to the lowest exposure quartile (p-trend=0.40). |
| [143] | Retrospective Nested Case-control. | N=327, 137 GDM. | 2012. | Patients who delivered at hospital in Xiamen, China. | Measured meconium levels of 4 metals: arsenic, cadmium, lead, and mercury; 1–2 days after delivery. | GDM. |
Arsenic and GDM: Adjusted OR=3.28 (95% CI: 1.24–8.71, p-value=0.017), 3.35 (95% CI: 1.28–8.75, p-value=0.014), and 5.25 (95% CI: 1.99–13.86, p-value=0.001) for women in the 2nd, 3rd, and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile (p-trend <0.001). Mercury and GDM: Adjusted OR=1.68 (95% CI: 0.72–3.89, p-value=0.228), 1.69 (95% CI: 0.72–3.96, p-value=0.226), and 1.75 (95% CI: 0.76–4.03, p-value=0.185) for women in the 2nd, 3rd, and 4th exposure groups, respectively, compared to the lowest exposure quartile (p-trend =0.004). Lead and GDM: Adjusted OR=0.37 (95% CI: 0.16–0.86, p-value=0.020), 0.16 (95% CI: 0.06–0.44, p-value <0.001), and 0.90 (95% CI: 0.46–1.78, p=value=0.772) for women in the 2nd, 3rd, and 4th exposure groups, respectively, compared to the lowest exposure quartile (p-trend=0.498). Chromium and GDM: Adjusted OR=1.74 (95% CI: 0.51–5.96, p-value=0.377), 1.65 (95% CI: 0.45–6.10, p-value=0.450), and 4.48 (95% CI: 1.40–14.31, p-value=0.011) for women in the 2nd, 3rd, and 4th exposure groups, respectively, compared to the lowest exposure quartile (p-trend=0.002). Cadmium and GDM: 3.07 (95% CI: 0.69–13.74, p-value <0.001), 16.87 (95% CI: 4.19–67.86, p-value <0.001), and 11.95 (95% CI: 2.97–48.04, p-value=0.142) for women in the 2nd, 3rd, and 4th exposure groups, respectively, compared to the lowest exposure quartile (p-trend <0.001). |
| [140] | Prospective Cohort. | N=1151, 14 GDM, 105 IGT. | 2009–2016. | Use of private well in household and participation in New Hampshire Birth Cohort Study, New Hampshire, USA. | Measured urine levels of total arsenic (iAs), metabolites [monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)], and methylation ratios (MMA/iAs and DMA/MMA) (once at 24–28 weeks gestation); toenail clippings (at 2 weeks postpartum); and home well water (once during pregnancy). | GDM, IGT. |
Arsenic and GDM Water: Adjusted OR=1.1 (95% CI: 1.0–1.2). Urine: Adjusted OR= 0.8 (95% CI: 0.3–2.4). Toenail: Adjusted OR= 4.5 (95% CI: 1.2–6.6). Arsenic and combined IGT and GDM Water: Adjusted OR=1.0 (95% CI: 0.9–1.1). Urine: Adjusted OR=1.0 (95% CI: 1.0–1.1). Toenail: Adjusted OR=0.9 (95% CI: 0.7–1.3). Arsenic and IGT Water: Adjusted OR=1.0 (95% CI: 0.9–1.1). Urinary: Adjusted OR=1.0 (95% CI: 1.0–1.1). Toenail: Adjusted OR=0.9 (95% CI: 0.6–1.3). |
| [138] | Prospective Cohort. | N=1274, 289 GDM, 59 IGT. | 2008–2011. | Participation in Maternal-Infant Research on Environmental Chemicals (MIREC) study at 10 sites in six provinces, Canada. | Measured blood levels of 4 metals: lead, cadmium, mercury, and arsenic; and urine levels of total BPA and 11 phthalates; once in 1st trimester. | GDM, IGT. |
Arsenic and GDM: Adjusted OR=0.7 (95% CI: 0.2–2.3), 2.5 (95% CI: 0.9–6.9), and 3.7 (95% CI: 1.4–9.6) for women in the 2nd, 3rd and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile (p-trend <0.01). Dose-response in cubic-spline model (p <0.01); test of linear null hypothesis (p-value=0.92). Arsenic and IGT: Adjusted OR=0.8 (95% CI: 0.4–1.8), 0.8 (95% CI: 0.3–1.9), and 1.2 (95% CI: 0.5–2.6) for women in the 2nd, 3rd and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile. Arsenic and combined GDM or IGT: Adjusted OR=0.8 (95% CI: 0.4–1.5), 1.3 (95% CI: 0.7–2.5), and 1.9 (95% CI: 1.1–3.5) for women in the 2nd, 3rd and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile (p-trend=0.01). Dose-response in cubic-spline model (p <0.03); test of linear null hypothesis (p-value=0.09). Cadmium and GDM: Adjusted OR=2.5 (95% CI: 1.0–6.4) for women in the highest cadmium exposure group compared to the lowest exposure quartile. |
| [141] | Semi-ecological. | N=5053, 268 GDM. | 2003, 2006, 2010. | Delivery at Clermont-Ferrand University Hospital in Auvergne, France. | Measured tap water levels of arsenic from routine testing of water supply units during 12-month period before birth. | GDM. | Arsenic and GDM: Adjusted OR=1.62 (95% CI: 1.01–2.53) for women in the high arsenic exposure group (≥ 10 μg/L) compared to the low arsenic exposure group (< 10 μg/L). When exposure was considered in three categories: Adjusted OR=1.43 (95% CI: 0.85–2.29) and 6.24 (95% CI: 1.64–19.49) for women in the 2nd and 3rd arsenic exposure groups (10–30 μg/L and ≥ 30 μg/L, respectively) compared to the lowest arsenic exposure group (< 10 μg/L). |
| [142] | Cross-sectional. | N=244, 21 GDM. | 2013–2014. | Patients at primary health centers in Arica, Chile. | Measured urine levels of inorganic arsenic once in 2nd trimester. | GDM. | Arsenic and GDM: Adjusted OR=2.98 (95% CI: 0.87–10.18) and 1.07 (95% CI: 0.26–4.33) for women in the 2nd and 3rd arsenic exposure groups, respectively, compared to the lowest tertile of exposure. |
| [147] | Prospective Cohort. | N=3260, 419 GDM. | 2013–2014. | Participation in Ma’anshan Birth Cohort Study in Anhui Province, China. | Measured blood levels of arsenic twice in 1st and 2nd trimesters, and cord blood levels once at delivery (3rd trimester). | GDM. |
Arsenic and GDM (1st
trimester): Adjusted OR=1.29 (95% CI: 0.92–1.82), 1.32 (95% CI: 0.94–1.85), and 1.71 (95% CI: 1.23–2.38) for women in the 2nd, 3rd, and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile. Incident GDM=12.53, 12.41, and 15.75 for women in the 2nd, 3rd, and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile (p-trend=0.001). Arsenic and GDM (2nd trimester): Adjusted OR=0.96 (95% CI: 0.71–1.31), 0.97 (95% CI: 0.71–1.32), and 0.89 (95% CI: 0.65–1.22) for women in the 2nd, 3rd, and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile. Incident GDM=13.82, 13.06, and 11.76 for women in the 2nd, 3rd, and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile (p-trend=0.211). Arsenic and GDM (3rd trimester): Adjusted OR=0.96 (95% CI: 0.67–1.37), 1.12 (95% CI: 0.79–1.58), and 1.39 (95% CI: 0.99–1.93) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile. Incident GDM=11.11, 12.52, and 14.73 for women in the 2nd, 3rd, and 4th arsenic exposure groups, respectively, compared to the lowest exposure quartile (p-trend=0.041). |
| [145] | Restrospectiv e Cohort. | N=6837. | 2012–2014. | Delivery at Wuhan Women and Children Medical Care Center in Wuhan, China. | Measured urine levels of cadmium (arsenic and chromium as potential confounders); once at delivery. | GDM. | Ln Cd and GDM: Adjusted RR=1.16 (95% CI: 1.03–1.33). When exposure was considered in four categories: Adjusted RR=1.21 (95% CI: 0.97–1.50), 1.24 (95% CI: 1.00–1.53), and 1.30 (95% CI: 1.05–1.61) for women in the 2nd, 3rd, and 4th exposure quartiles, respectively, compared to the lowest exposure quartile (p-trend <0.05). |
BPA = Bisphenol A; BP-3 = Benzophenone-3; CI = Confidence Interval; DDE = Dichlorodiphenyldichloroethylene; DDT = Dichlorodiphenyltricloroethane; Di-2-ethylhexyl phthalate metabolites (ΣDEHP = MEHHP, MECPP, MEOHP, and MEHP); HR = Hazard Ratio; HCB = Hexachlorobenzene; HCH = β-Hexachlorocyclohexane; IQR = Interquartile range; MnBP = Mono-n-butyl phthalate; MCiOP = Mono(carboxyisooctyl) phthalate; MCPP = Mono (3-carboxypropyl) phthalate; MECPP = Mono-(2-ethyl-5-carboxypentyl) phthalate; MEHP = Mono-(2-ethylhexyl) phthalate; MEP = Monoethyl phthalate; MiBP = Mono-isobutyl phthalate; OR = Odds Ratio; OCP = Organochlorine Pesticide; PFAS = Perfluoroalkyl substances; PFDeA = Perfluorodecanoic acid; PFHxS = Perfluorohexane sulfonate; PFNA = Perfluorononanoic acid; PFOSA = Perfluorooctane sulfonamide; PFOS = Perfluorooctane sulfonic acid; PFOA = Perfluorooctanoic acid; PFUA = Perfluoroundecanoic acid; PBPK = Physiologically based pharmacokinetic; PBDE = Polybrominated diphenyl ether; PCB = Polychlorinated biphenyl; PCDD = Polychlorinated dibenzo-p-dioxins. PCDF = Polychlorinated dibenzofurans. PIH = Pregnancy-induced hypertension; RR = Relative Risk; SD = Standard Deviation.