| Objective: In order to provide new epidemiological evidence for comprehending the relationships between heavy metal concentrations and the development of preeclampsia(PE),the present study explore the associations of heavy metal concentrations and serum hormone levels with PE and the relationships between heavy metal concentrations and serum hormone levels,and whether serum hormones play the mediating roles in the relationships between heavy metal concentrations and PE.Methods: In the present study,160 PE patients were selected as the case group,and 160 healthy pregnant women as the control group among pregnant women who were admitted to the Songshan Lake Central Hospital in Dongguan City for delivery between October 2020 and October 2022.After obtaining informed consent,a venous blood sample was collected from the subject,and the medical record was used to obtain demographic information,disease history and pregnancy history.Inductively coupled plasma mass spectrometer was used to determine concentrations of manganese(Mn),nickel(Ni),copper(Cu),zinc(Zn),arsenic(As),cadmium(Cd)and lead(Pb).Electrochemiluminescence was used to determine the levels of β-human chorionic gonadotropin(β-h CG),estradiol(E2),progesterone(P),testosterone(T),cortisol(Cort)and cortisone(Cor)in serum.Logistic regression,restricted cubic splines(RCS),weighted quantile sum(WQS),bayesian kernel machine regression(BKMR)models,multiple linear regression,and mediation analysis model were used to analyze the associations of heavy metal concentrations and serum hormone levels with PE.Results:(1)Associations between single exposure to heavy metal and PE.Serum Mn concentrations were lower(9.63 μg/L)in the case group compared to the control group(12.84 μg/L).However,serum Cu and Zn concentrations were higher(2.17 mg/L and 0.72 mg/L)in the case group compared to the control group(1.95 mg/L and 0.64 mg/L).Logistic regression analysis showed that compared with low concentrations,high Mn concentrations reduced the risk of PE(OR = 0.27,95% CI: 0.09 ~ 0.85),middle Ni concentrations reduced the risk of PE(OR = 0.39,95% CI: 0.22 ~ 0.69),high Cu and Zn concentrations increased the risk of PE(OR = 3.97,95% CI: 1.61 ~ 9.82 and OR = 6.55,95% CI: 2.36 ~ 18.20).Further analysis revealed that high Cd concentrations increased the risk of PE(OR = 2.50,95% CI: 1.01 ~ 6.20)after adjusting for potential covariates and other heavy metals.The RCS revealed a non-linear doseresponse relationship between Ni,Cu,Zn,Cd,Cu and the risk of PE.Once heavy metal concentrations reachedcertain levels,the risk of PE increased as concentrations rose.(2)Associations between combined exposure to heavy metals and PE.The WQS model analysis showed that both the positive WQS index and the negative WQS index for combined exposure to heavy metals were associated with the risk of PE.In the positive association model,Zn(0.46)received the highest weight,followed by Cd(0.28)and Cu(0.19),indicating that Zn exposure contributed more to the positive association between WQS and PE.In the negative association model,Mn(0.54)received the highest weight,indicating that Mn exposure contributed more to the negative association between WQS and PE.The BKMR model analysis shows that Mn,Cu and Zn had greater posterior inclusion probabilities(PIPs).When other heavy metals were fixed at the median,Mn showed a negative exposure-response relationship with PE,whereas Zn and Cu showed a positive exposure-response relationship with PE.In addition,we did not find any interaction among heavy metals.In general,with rising concentrations of heavy metal,the risk of PE prevalence tended to rise.(3)Associations between serum hormone levels and PE.The median concentrations of E2,Cort and Cort/Cor were lower in the PE group compared to the control group.However,β-h CG and T were higher in the PE group compared to the control group(P < 0.05).Logistic regression analysis demonstrated that compared to low concentrations,high concentrations of β-h CG and T increased the risk of PE(OR = 3.24,95% CI: 1.49 ~ 7.05 and OR = 10.06,96% CI: 4.35 ~ 23.29),while high concentrations of E2 and Cort decreased the risk of PE(OR = 0.36,95% CI: 0.14 ~ 0.90 and OR = 0.28,95% CI: 0.09 ~ 0.80).In addition,middle and high concentrations of Cort/Cor were negatively associated with PE compared to low concentrations(OR = 0.44,95% CI: 0.21 ~ 0.93 and OR = 0.36,95% CI: 0.17 ~ 0.77).The dose-response association of β-h CG and P with the risk of PE showed a U-shape,with the risk of PE decreasing with increasing serum hormone levels at low levels and increasing with increasing serum hormone levels at high levels.In addition,with rising the serum levels of Cort/Cor,the risk of PE tended to decrease.(4)Associations of heavy metal concentrations with serum hormone levels.After adjusting for potential covariates,linear regression analysis showed that Cu was positively associated with β-h CG.Mn,Cu,and Zn were positively associated with E2.Cd was negatively associated with E2 and P.Cu was positively associated with T.Ni was negatively associated with Cort.Cu was positively associated with Cort.The RCS analysis showed a significant non-linear dose-response relationship between Mn and β-h CG.At low levels,β-h CG concentrations gradually decreased with increasing Mn concentrations.There was a non-linear dose-response association between Zn and E2,with E2 levels gradually rising with increasing Zn concentration when the Zn concentration was raised over 0.72 mg/L.The dose-response relationship between Ni,Zn,and P showed a U-shape.In detail,P levels gradually decreased with rising heavy metal concentrations at low levels,and increased with rising heavy metal concentrations at high levels.The dose-response relationship between Zn and T showed a U-shape,with T levels decreased with rising Zn concentrations at low levels and with increased with rising Zn concentrations at high levels when Zn concentrations exceeded 1.42 mg/L.Ni showed a significant non-linear association with Cort.When the Ni concentrations exceeded 3.95 μg/L,Ni exposure was negatively associated with Cort levels.The WQS model discovered a significant association between the WQS positive index for combined exposure to heavy metals and E2,P levels(OR = 1.09,95% CI: 1.01 ~ 1.18 and OR = 1.15,95% CI: 1.08 ~ 1.22),with Zn(0.85)having the highest weight in the relationship between the positive WQS index and E2,and Cu(0.74)having the highest weight in the relationship between the positive WQS index and P.(5)Mediation effect of serum hormone levels in the associations between heavy metal concentrations and PE.Mediation analysis showed that E2 mediated the associations of Cu and Zn with PE.P mediated the associations of Cu with PE.Furthermore,T mediated the association of Cu with PE.Cort mediated the associations of Cu and Zn with PE.In addition,Cort/Cor mediated the association of Cu with PE.Conclusion: In the present study,high Mn concentration reduced the risk of PE,while high concentrations of Cu and Zn increased the risk of PE.Combined exposure to heavy metals could increase the risk of PE.Heavy metal exposure can cause changes in serum hormone(E2 and Cort)levels,which in turn can have an effect on PE. |
PDF Full Text Request