Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study
Background: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the ris...
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Elsevier
2023-01-01
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author | Shanshan Shao Weijun Pan Baolin Wang Yuwei Liu Hong Gan Mengdie Li Tierong Liao Xinliu Yang Qianhui Yang Cun Huang Menglong Geng Guixia Pan Kaiyong Liu Peng Zhu Fangbiao Tao |
author_facet | Shanshan Shao Weijun Pan Baolin Wang Yuwei Liu Hong Gan Mengdie Li Tierong Liao Xinliu Yang Qianhui Yang Cun Huang Menglong Geng Guixia Pan Kaiyong Liu Peng Zhu Fangbiao Tao |
author_sort | Shanshan Shao |
collection | DOAJ |
description | Background: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. Methods: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20–49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography–triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). Results: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. Conclusion: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors. |
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spelling | doaj.art-4897c63df1ab4c528db535630bb553e62023-01-05T04:30:35ZengElsevierEcotoxicology and Environmental Safety0147-65132023-01-01249114414Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control studyShanshan Shao0Weijun Pan1Baolin Wang2Yuwei Liu3Hong Gan4Mengdie Li5Tierong Liao6Xinliu Yang7Qianhui Yang8Cun Huang9Menglong Geng10Guixia Pan11Kaiyong Liu12Peng Zhu13Fangbiao Tao14School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaClinical Center of Reproductive Medicine, Ma'anshan Maternal and Child Health Hospital, Ma'anshan, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaClinical Center of Reproductive Medicine, Ma'anshan Maternal and Child Health Hospital, Ma'anshan, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, ChinaSchool of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, China; Correspondence to: Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.Background: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. Methods: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20–49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography–triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). Results: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. Conclusion: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.http://www.sciencedirect.com/science/article/pii/S0147651322012544AntibioticsBiomonitoringUrine samplesFemale infertility |
spellingShingle | Shanshan Shao Weijun Pan Baolin Wang Yuwei Liu Hong Gan Mengdie Li Tierong Liao Xinliu Yang Qianhui Yang Cun Huang Menglong Geng Guixia Pan Kaiyong Liu Peng Zhu Fangbiao Tao Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study Ecotoxicology and Environmental Safety Antibiotics Biomonitoring Urine samples Female infertility |
title | Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study |
title_full | Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study |
title_fullStr | Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study |
title_full_unstemmed | Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study |
title_short | Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study |
title_sort | association between antibiotic exposure and the risk of infertility in women of childbearing age a case control study |
topic | Antibiotics Biomonitoring Urine samples Female infertility |
url | http://www.sciencedirect.com/science/article/pii/S0147651322012544 |
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