Part 1 PAHs exposure level of pregnant women in Zunyi and its influencing factors Objective: To detect the concentration of urinary OH-PAHs in pregnant women,describe the distribution of OH-PAHs,and analyze the predictors of urinary OH-PAHs concentration in pregnant women.Methods: During May 12,2020 to October 19,2021,in the medical university first affiliated hospital of zunyi,zunyi medical college second affiliated hospital,Meitan county people’s hospital and Xi Shui County people’s hospital,recruiting pregnant women whose were not serious infectious and chronic diseases,such as chronic cardiovascular disease,cancer,chronic renal failure and HIV infection.After signing informed consent,all participants were asked to complete face-to-face electronic questionnaires and urine samples were collected.The concentration of OH-PAHs was measure by Gas chromatography-triple quadrupole mass spectrometry(GC-MS/MS).Includes 1-OH-NAP,2-OH-NAP,2-OH-FLU,9-OH-FLU,1-OH-PHE,2-OH-PHE,3-OH-PHE,4-OH-PHE,9-OH-PHE,and 1-OH-PYR.The concentration of OH-PAHs as the dependent variable and demographic factors as the independent variable,the generalized linear model was used to analyze the predictor factors of OH-PAHs exposure in pregnant women.Results: A total of 5789 population were recruited,and 3140 completed questionnaires and provided urine samples.The detection rates of 1-OH-NAP,2-OH-NAP,2-OH-flu,9-OH-FLU,1-OH-PHE,2-OH-PHE,3-OH-PHE,4-OH-PHE,9-Oh-PHE and 1-Oh-PYR were 68.90%,74.32%,90.74% and 83,55%,78.49%,72.63%,78.52%,57.22%,79.09%,71.63%respectively.The concentrations of before creatinine correction were 0.53 μg/L,0.42 μg/L,0.36 μg/L,0.34 μg/L,0.08 μg/L,0.10 μg/L,0.02 μg/L,0.02 μg/L,0.02 μg/L,respectively.The concentrations by creatinine corrected were 0.47 μg/g Cr,0.45 μg/g Cr,0.34 μg/g Cr,0.31 μg/g Cr,0.07 μg/g Cr,0.06 μg/g Cr,0.10 μg/g Cr,0.03 μg/g Cr,0.02μg/g Cr,and 0.02 μg/g Cr respectively.The correlation among metabolites ranged from weak to moderate.The spearman correlation coefficient of 2-OH-Flu and 9-OH-Flu was0.67,that of 3-OH-PHE was 0.62,and that of 1-OH-PHE was 0.61.Spearman correlation coefficients between 1-OH-PRY and 2-OH-NAP,2-OH-FLU,9-OH-FLU,1-OH-PHE,2-OH-PHE,3-OH-PHE and 9-OH-PHE were 0.10,0.21,0.25,0.24,0.22,0.11 and 0.29 respectively,spearman correlation coefficient between 2-OH-NAP and 9-OH-PHE was0.24.Spearman correlation coefficients between the any other two metabolites ranged from0.30 to 0.59.Using generalized linear model analysis,it was found that the levels of urinary OH-PAHs in pregnant women who used fuel for cooking,lived near the main traffic road,had never given birth to children,were not planned for pregnancy had moderate to high annual household income,were overweight,and had low education level were significantly higher than those in the control population: the exposure levels of2-OH-NAP(β=0.89,95%CI,0.59-1.20)and 9-OH-Flu(β=0.33,95%CI,0.10-0.55)in pregnant women who used fuel for cooking were significantly higher than those who used electricity for cooking.Exposure to 9-OH-PHE,1-OH-PHE,and 4-OH-PHE is higher in pregnant women between 5 and 100 meters than in women with distance greater than 100 meters from housing to traffic.The exposure to 1-OH-NAP,2-OH-NAP,2-OH-FLU,9-OH-FLU,2-OH-PHE,3-OH-PHE,4-OH-PHE and 1-OH-PYR was higher in pregnant women less than 5 meters.The exposure to 2-OH-NAP,9-OH-FLU and 9-OH-PHE was lower in those who had given birth.The exposure to 2-OH-NAP,2-OH-PHE,3-OH-PHE and 4-PEH was lower in pregnant women with planned pregnancy.Compared with pregnant women with low annual household income,pregnant women with medium annual household income were exposed to higher levels of 2-OH-FLU,9-OH-Flu,1-OH-PHE,2-OH-PHE,3-OH-PHE and 4-OH-PHE.Pregnant women with high annual household income had higher exposure to 2-OH-FLU,1-OH-PHE,2-OH-PHE,3-OH-PHE,4-OH-PHE and 9-PEH.Overweight pregnant women had higher exposure to 1-OH-NAP,2-OH-NAP,2-OH-flu,9-OH-Flu,1-OH-PHE,2-OH-PHE,3-OH-PHE,4-OH-PHE and1-OH-PYR.The exposure to 2-OH-NAP,9-OH-FLU and 2-OH-PHE of pregnant women with secondary education was lower than that of pregnant women with lower education,while that of pregnant women with higher education was lower.Conclusion: Except for the lower concentrations of 1-OH-NAP and 2-OH-NAP,the concentration of urinary OH-PAHs in pregnant women in Zunyi was similar to that in economically developed areas.We found those used fuel for cooking,and the distance between houses and main traffic roads was shorter,low education level are at high risk of PAH exposure and may be at risk of PAH exposure.Measures should be taken to reduce the PAH exposure level of these high-risk groups to protect maternal and fetal health.Part 2 The relationship between exposure to OH-PAHs in early pregnancy and spontaneous abortionObjective: To explore the correlation between OH-PAHs and spontaneous abortion in pregnant women.Methods: 1445 were registered,111 of whom had spontaneous abortion,and the incidence of spontaneous abortion was 7.69%.The study population was from the pregnancy cohort of Zunyi,southwest China,and volunteers were recruited in the First Affiliated Hospital of Zunyi Medical University,the Second Affiliated Hospital of Zunyi Medical University,Meitan County People’s Hospital,and Xishui County People’s Hospital.Women who are confirmed to be pregnant and free of serious chronic or infectious diseases(such as cancer,chronic cardiovascular disease,chronic kidney failure and HIV infection)are eligible to participate.After the informed consent was signed,all participants completed face-to-face electronic questionnaires and urine samples were collected.GC-MS /MS was used to detect PAH metabolic concentration.Includes 1-OH-NAP,2-OH-NAP,2-OH-FLU,9-OH-FLU,1-OH-PHE,2-OH-PHE,3-OH-PHE,4-OH-PHE,9-OH-PHE,and 1-OH-PYR.Follow up pregnant women until abortion,delivery,or termination of pregnancy for other reasons.The ratio of case group to control group was 1:1 according to maternal age(±2)and gestational week(±1),and the relationship between PAH metabolite concentration and spontaneous abortion was analyzed.Results: A total of 1018 pregnant women were recruited in the early stages of pregnancy and follow-up was completed.There were 77 cases and 77 pairs were successfully matched.The number of pregnancies in the control group was significantly lower than those in the case group(P=0.005).The passive smoking rate of pregnant women in the control group was significantly lower than that in the case group(P<0.001).Pregnant women who drink alcohol in the control group were significantly less than those who drink alcohol in the case group(P=0.003).The proportion of pregnant women’s husbands drinking more than 1 time per week in the control group was significantly lower than those who in the case group(P=0.005).Univariate analysis showed that 2-OH-NAP in case group was significantly higher than that in control group(P=0.002).Logistic regression analysis of OH-PAHs after lg conversion showed that without adjusting for any confounding factors,the risk of spontaneous abortion increased by 2.33-fold for every 1 unit increase of lg2-OH-NAP in urine of pregnant women(OR=2.33,95%CI: 1.38-3.93),P=0.002.After adjusting for History of abortion,the risk of spontaneous abortion increased 2.36-fold for each unit increase in urine lg2-OH-NAP(OR=2.36,95%CI: 1.39-4.00),P=0.001.After further adjustment was made for the number of pregnancies,passive smoking,alcohol consumption and frequency of alcohol consumption by the husband,the risk of spontaneous abortion increased 2.39-fold for each unit increase in lg2-OH-PHE(OR=2.39,95%CI: 1.34-4.26),P=0.003.The 2-OH-NAP was further analyzed by ROC analysis,and the ROC curve for predicting spontaneous abortion was drawn.The area under the curve was 0.644,and the 95%CI was 0.557~0.732,P=0.002.When the concentration of 2-OH-NAP was 0.33μg/g Cr,the corresponding correct diagnostic index was the largest,which was 26%.The sensitivity and specificity were 58.44% and 67.53% respectively.Restricted cubic spline analysis showed that when lg2-OH-NAP was less than-0.54(that is,the level of 2-OH-NAP was 0.29 μg/g Cr),OR did not change significantly.When lg2-OH-NAP was above 0.29μg/g Cr,OR gradually increased with the increase of 2-OH-NAP level.Conclusion: PAH metabolite 2-OH-NAP exposure during gestation was an independent risk factor for spontaneous abortion,which significantly increased the risk of spontaneous abortion in pregnant women.The 2-OH-NAP concentration of 0.33μg/g Cr was the cut-off point for predicting spontaneous abortion,but the overall predictive power was limited.When 2-OH-NAP level was lower than 0.29 μg/g Cr,the risk of spontaneous abortion did not change significantly with the change of 2-OH-NAP level.When 2-OH-NAP was greater than 0.29 μg/g Cr,the risk of spontaneous abortion increased with the increase of 2-OH-NAP level. |