Assessment Of The Correlation And Cumulative Health Risk Of Antibiotic Exposure In Couples Of Childbearing Age

ObjectivesTo describe the distribution characteristics and co-exposure patterns of 40 antibiotics and two metabolites,to evaluate the cumulative health risk assessment of low dose long-term continuous exposure to antibiotics,and to explore the correlation and influencing factors of exposure level of couples in reproductive health of childbearing couples of Anhui province.MethodsThis study included 1 500 couples of reproductive age from Reproductive Health of Childbearing Couples-Anhui Cohort.Demographic information,lifestyle and dietary habits of the included couples were collected using self-designed baseline questionnaires from August 2019 to August 2020.At the same time,urine samples of the couple were collected and frozen separately in a-80 ℃ refrigerator.A stratified sample of 1,500 randomly selected couples of reproductive age who had completed the first healthy follow-up was used for testing.From August 2021 to December 2021,40 antibiotics and 2 metabolites exposure levels in urine samples of couples were detected by liquid chromatography-triple quadrupole tandem mass spectrometry,and urine specific gravity value was detected by urine hydrometer.The distribution of positive detection rate and exposure level of antibiotics in couples was described by converting the original concentration below the detection limit and calculating the concentration of antibiotics in urine corrected by specific gravity.Cumulative exposure to antibiotics in couples was assessed by calculating daily intake estimates,hazard quotient/hazard index;To illustrate the correlation between antibiotic exposure in couples by spearman correlation analysis,to reveal the gender difference between antibiotic exposure in couples by paired t test,and to analyze the influencing factors of antibiotic exposure level in families,to analyze the correlation between the proportion correction concentration of antibiotics in urine and demographic characteristics by GLMs,then,to find out the influencing factors related to antibiotic exposure level.ResultsThere were significant differences in demographic information such as age,body mass index and education level among the included couples（n = 1 500）.The total detection rates of all antibiotics were 98.9% and 99.3%,respectively.The detection rates of VAs and PVAs were above 90%.The highest detection rates of eight antibiotics were sulfonamides and fluoroquinolones.The detection rate of coexposure of antibiotics in couples was similar to that in couples,and the single antibiotic with the highest detection rate was trimethoprime（60.1%）.The range of antibiotic concentration corrected by urinary specific gravity was basically consistent with the original concentration.Regardless of single antibiotic or different use antibiotics,the husband’s antibiotic concentration was always higher than the wife’s,especially in HAs and PHAs,but not significantly in VAs and PVAs.Wilcoxon signed-rank test showed that there were significant differences in the original and SG adjusted concentrations of chloramphenicol and lincomycin antibiotics between the couple.About four-fifths of couples of reproductive age were simultaneously exposed to at least three different uses of antibiotics,and more than half had low levels of antibiotic exposure.The total EDI of antibiotics in couples was concentrated in 0.20～0.50 μg/kg/day,and the total EDI of antibiotics in couples was less than 1.00 μg/kg/day in about two-thirds of couples.HQ or HI > 1 indicates that the couple is facing potential health risks.The proportion of Ciprofloxacin HQ > 1 was the highest,which was 2.0% in wives and 1.4% in husbands,respectively.Among all antibiotics in couples,the same antibiotics showed a low to moderate correlation between couples,among which macrolides（r = 0.51,P < 0.01）,tetracycline（r = 0.63,P < 0.01）,and lincomycin（r = 0.55,P < 0.01）showed a moderate correlation.There were significant differences in exposure levels between couples with18 single antibiotics.The exposure level of four kinds of antibiotics in northern Anhui was much higher than that in central Anhui,The exposure level of HAs and PHAs in southern Anhui were lower than those in central Anhui.The exposure level of PVAs in spring were higher than those in other three seasons,while the exposure levels of macrolides and lincomycin were higher in spring.The results were similar between husbands and wives.ConclusionsIn Anhui province,antibiotic exposure of couples of child-bearing age was mainly in low dose long-term continuous exposure mode.PVAs including ciprofloxacin were confirmed to have potential health risks to human body.Antibiotic exposure levels were correlated between couples,with gender differences.Residence and urine sampling season were important factors affecting the distribution of antibiotic exposure.This study provides new research evidence for the exploration of factors affecting reproductive health of couples of child-bearing age,and also provides potential ideas for the influence of pre-pregnancy environmental cumulative exposure on fertility.