期刊
JAMA NETWORK OPEN
卷 5, 期 7, 页码 -出版社
AMER MEDICAL ASSOC
DOI: 10.1001/jamanetworkopen.2022.20176
关键词
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资金
- NIEHS [R21ES029681, R01ES029944, R01ES030364, R21ES028903, P30ES007048, R21ES029328, R01ES028903, P30ES023515]
- European Community [308333]
- Instituto de Salud Carlos III
- Centro de Investigacion Biomedica en Red Epidemiologia y Salud Publica
- Generalitat de Catalunya-CIRIT
- Lithuanian Agency for Science Innovation and Technology [6-04-2014_31V-66, 31V-77]
- Etude des Determinants Pre et Postnatals du Developpement et de la Sante de l'Enfant (EDEN)
- Norwegian Ministry of Health and Care Services
- Ministry of Education and Research
- European projects
- Greek Ministry of Health
- Wellcome Trust [101597]
- UK Medical Research Council [MR/N024391/1]
- UK Economic and Social Science Research Council
- National Institute for Health Research Yorkshire and Humber Applied Research collaboration
- Instituto de Salud Carlos III [CP16/00128]
- European Social Fund Investing in Your Future
- Juan de la Cierva-Incorporacion fellowship - Spanish Ministerio de Economia, Industria y Competitividad [IJC2018-035394-I]
- Centro de Excelencia Severo Ochoa 2019-2023 Program from the Spanish Ministry of Science and Innovation [2018-000806-S]
- Generalitat de Catalunya through the Centres de Recerca de Catalunya Program
Prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase the risk of liver injury in children. Specific EDCs, including organochlorine pesticides, PBDEs, perfluoroalkyl substances, and metals, were associated with an increased risk of liver injury, while high-molecular-weight phthalates and phenols were associated with a decreased risk. Additionally, polychlorinated biphenyls and PBDEs were associated with higher levels of hepatocellular apoptosis. These findings suggest that prenatal exposure to EDCs may be a potential risk factor for pediatric nonalcoholic fatty liver disease.
IMPORTANCE Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. OBJECTIVE To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. EXPOSURES Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. MAIN OUTCOMES AND MEASURES Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. RESULTS The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (beta, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (beta, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. CONCLUSIONS AND RELEVANCE With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.
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