| Backgroud:According to the World Health Organization(WHO),the American Society for Reproductive Medicine(ASRM),the International Committee for Monitoring Assisted Reproductive Technology(ICMART),Recurrent spontaneous abortion(RSA)has been defined as two consecutive unexplained terminations of pregnancy before 20 weeks.The prevalence of RSA has been reported to be as high as 3%-5%in the clinic,but the causes of RSA remain unexplained for approximately 50%of the women who experience RSA.Recently,heavy metal,PAEs may increase the risk of URSA,but the results was confilct.Recent years,oxidative stress has been implicated in the mechanis-m of URSA,the oxidative stress state may be related to the exposure of heavy metal,PAEs.Therefore,the association of heavy metal and PAEs exposure and oxidative stress with URSA is a public health issue that needs to be focused on the development of women and children health.Object:The study aims to explore the association of heavy metal and PAEs exposure and oxidative stress with URSA and provide suggestion to control the impact of environment pollution on the URSA.Method:We collected 96 URSA patients who were from the Beijing Maternal and Child Health Care Hospital affiliated to Capital Medical University from April to October 2018 as a case group.We tried to match 1 control of pregnant women with no history of adverse pregnancy in the same hospital with the following criteria:age(±3years),gestational age(±2 week).We used the questionare to collect the personal and family informations,and collected the blood sample 12ml,urine sample 50ml.We used the ICP-MS method to detect the level of lead,arsenic,cadimium,chromium and the HPLC-MS/MS method to detect the level of PAEs,also the ELSA method was used to detect the level of the biomarkers of oxidative stress(8-iso-PGF2a,8-OHdG).We used the linear regression to analyse the influence factors of heavy metals and PAEs.We used the conditional logistic regression to evaluate the association of heavy metals and PAEs exposure with the risk of URSA.In addition,we explored the association of heavy metals and PAEs exposure with oxidative stress in the URSA patients and normal pregnancy controls,respectively.Results:(a)The geomean value of blood arsenic level in the case group was 1.68μg/L(95%CI:1.50～1.86),significantly higher than in the control group of 1.26μg/L(95%CI:1.17～1.37)(P<0.001).After adjusting for confounding factors,compared to the group with blood lead level<7.00μg/L,the URSA odds ratios for the group with lead levels(>11.0μg/L)were 2.53(95%CI:1.08-5.91).Compared to the group with blood arsenic level(<1.00μg/L),the URSA odds ratios for the group with blood arsenic level(>1.50μg/L)were 2.62(95%CI:1.04-6.60).No significant differences in the blood cadmium were found in the URSA odds ratios.The blood lead level of URSA patients was positively related to tobacco exposure(p=0.291,P=0.004),blood arsenic level was also positively related to the frequency of eating internal organs of animals(≥1 time/month)(β=0.231,P=0.020),blood lead and arsenic level were different in different profession groups;Urinary cadmium level was positively associated with age(β=0.240,P=0.021).In the control group,the blood lead level was positively related to the frequency of eating internal organs of animals(≥1 time/month)(P=0.266,P=0.009)and the blood cadmium level was related to age and breakfast for take-out(β=0.255,P<0.001;β=0.240,P=0.024),the urinary cadmium level was related to the location(P=0.240,P=0.034).(b)The urinary level of MEHHP(>10.00μg/g)was significantly associated with elevated risk for URSA(OR =2.93,95%C1:1.08-7.94).The urinary level of MnBP was related to dinner for take-out(β=0.20,P=0.040).(c)After adjusting for creatinine,urinary 8-iso-PGF2a concentration(GM:42.53μg/g,95%CI:37.82～48.11)was significantly higher in the case group than in the control group(GM:31.11μg/g,95%CI:27.33～35.42)(P=0.001).Urinary 8-OHdG concentration(GM:4.86μg/g,95%CI:4.25～5.62)was significantly higher in the case group than in the control group(GM:3.84μg/g,95%CI:3.35-4.43)(P<0.001).After adjusting for possible confounders,there was a weak correlation between middle urinary 8-iso-PGF2a level and URSA(OR=2.80,95%CI:0.97-8.05),and high urinary 8-iso-PGF2a level increased the odds ratio of URSA(OR=3.45,95%CI:1.28～9.25).However,We did not find the association between urinary 8-OHdG level and URSA After adjusting for the confounding factors,urinary 8-iso-PGF2a levels were positively correlated with urinary lead and urinary chromium levels(P<0.001,P<0.001),MEHP levels of PAEs metabolites(P=0.025)in the case group;urinary 8-OHdG level was positively correlated with urinary lead and urinary chromium level(P=0.005,P<0.001).In the control group,urinary 8-iso-PGF2a level was positively correlated with urinary lead,urinary cadmium,urinary arsenic,urinary chromium levels(P=0.005,P=0.003,P=0.003,P<0.001),also with PAEs metabolites of MiBP,MEHP,MEHHP,and MEOHP levels(P=0.021,P=0.002,P=0.005,P=0.021);urinary 8-OHdG level was positively correlated with urinary lead,urinary arsenic and urinary chromium levels(P=0.026,P=0.001,P<0.001),also with MEHP,MEHHP,and MEOHP levels of PAEs metabolites(P=0.002,P=0.006,P=0.019).Conclusion:(a)The blood arsenic concentration in the URSA group was significantly higher than that in the control group.In addition,high blood lead and urinary MEHHP also had an increased risk of URSA.The results suggest that heavy metals,PAEs could be related to the risk of URSA.(b)The influencing factors of heavy metals exposure in URSA patients were related to age,tobacco exposure during pregnancy,occupation and personal dietary habits.The influencing factors of heavy metals exposure in normal pregnancy were related to age,tobacco exposure during pregnancy,occupation,personal dietary habits and location Moreover,the level of urinary MnBP was related to occupation and eating take-out for dinner during pregnancy in normal pregnancy(c)The oxidative stress biomarker of 8-iso-PGF2a was related to the risk of URSA,the result suggested that oxidative stress is related to the risk of URSA.In addition,the positive relationship between heavy metals,PAEs metabolites exposure and the biomarker of oxidative stress 8-iso-PGF2a,8-OHdG was observed in URSA patients. |
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