Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism.
Autism spectrum disorder
Cadmium
Epidemiology
ExWAS
Metals exposure
Pregnancy cohort
Journal
Environmental health : a global access science source
ISSN: 1476-069X
Titre abrégé: Environ Health
Pays: England
ID NLM: 101147645
Informations de publication
Date de publication:
05 Jul 2024
05 Jul 2024
Historique:
received:
23
01
2024
accepted:
25
06
2024
medline:
6
7
2024
pubmed:
6
7
2024
entrez:
5
7
2024
Statut:
epublish
Résumé
Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized. In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts. In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD. Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.
Sections du résumé
BACKGROUND
BACKGROUND
Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.
METHODS
METHODS
In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts.
RESULTS
RESULTS
In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD.
CONCLUSION
CONCLUSIONS
Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.
Identifiants
pubmed: 38970053
doi: 10.1186/s12940-024-01101-2
pii: 10.1186/s12940-024-01101-2
doi:
Substances chimiques
Metals, Heavy
0
Environmental Pollutants
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
62Informations de copyright
© 2024. The Author(s).
Références
American Psychiatric Association. APA Publishing information: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders : DSM-5. 5th ed. American Psychiatric Association Publishing; 2013.
Maenner MJ, Warren Z, Williams AR, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2020. MMWR Surveill Summ. 2023;72(2):1–14. https://doi.org/10.15585/mmwr.ss7202a1 .
doi: 10.15585/mmwr.ss7202a1
Rogge N, Janssen J. The economic costs of autism spectrum disorder: a literature review. J Autism Dev Disord. 2019;49(7):2873–900. https://doi.org/10.1007/s10803-019-04014-z .
doi: 10.1007/s10803-019-04014-z
Cakir J, Frye RE, Walker SJ. The lifetime social cost of autism: 1990–2029. Res Autism Spectr Disord. 2020;72(January):1–18. https://doi.org/10.1016/j.rasd.2019.101502 .
doi: 10.1016/j.rasd.2019.101502
Keyes KM, Susser E, Cheslack-postava K, Fountain C, Liu K, Bearman PS. Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California. Int J Epidemiol. 2012;41(2):495–503. https://doi.org/10.1093/ije/dyr193 .
doi: 10.1093/ije/dyr193
Hansen SN, Schendel DE, Parner ET. Explaining the increase in the prevalence of autism spectrum disorders: the proportion attributable to changes in reporting practices. JAMA Pediatr. 2015;169(1):56–62. https://doi.org/10.1001/jamapediatrics.2014.1893 .
doi: 10.1001/jamapediatrics.2014.1893
Worley JA, Matson JL, Sipes M, Kozlowski AM. Prevalence of autism spectrum disorders in toddlers receiving early intervention services. Res Autism Spectr Disord. 2011;5(2):920–5. https://doi.org/10.1016/j.rasd.2010.10.007 .
doi: 10.1016/j.rasd.2010.10.007
Ding M, Shi S, Qie S, Li J, Xi X. Association between heavy metals exposure (cadmium, lead, arsenic, mercury) and child autistic disorder: a systematic review and meta-analysis. Front Pediatr. 2023;11:1169733. https://doi.org/10.3389/fped.2023.1169733
doi: 10.3389/fped.2023.1169733
Jafari T, Rostampour N, Fallah AA, Hesami A. The association between mercury levels and autism spectrum disorders: a systematic review and meta-analysis. J Trace Elem Med Biol. 2017;44(May):289–97. https://doi.org/10.1016/j.jtemb.2017.09.002 .
doi: 10.1016/j.jtemb.2017.09.002
Zhang J, Li X, Shen L, et al. Trace elements in children with autism spectrum disorder : a meta-analysis based on case-control studies. J Trace Elem Med Biol. 2021;67(May):126782.
doi: 10.1016/j.jtemb.2021.126782
Saghazadeh A, Rezaei N. Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79(July):340–68. https://doi.org/10.1016/j.pnpbp.2017.07.011 .
doi: 10.1016/j.pnpbp.2017.07.011
Rashaid AHB, Nusair SD, Alqhazo MT, Adams JB, Abu-Dalo MA, Bashtawi MA. Heavy metals and trace elements in scalp hair samples of children with severe autism spectrum disorder: a case-control study on Jordanian children. J Trace Elem Med Biol. 2021;67(May). https://doi.org/10.1016/j.jtemb.2021.126790 .
Baj J, Flieger W, Flieger M, et al. Autism spectrum disorder: trace elements imbalances and the pathogenesis and severity of autistic symptoms. Neurosci Biobehav Rev. 2021;129(July):117–32. https://doi.org/10.1016/j.neubiorev.2021.07.029 .
doi: 10.1016/j.neubiorev.2021.07.029
Martin EM, Fry RC. Environmental influences on the epigenome: exposure- associated DNA methylation in human populations. Annu Rev Public Health. 2018;39:309–33. https://doi.org/10.1146/annurev-publhealth-040617-014629 .
doi: 10.1146/annurev-publhealth-040617-014629
Watson CV, Lewin M, Ragin-Wilson A, et al. Characterization of trace elements exposure in pregnant women in the United States, NHANES 1999–2016. Environ Res. 2020;183. https://doi.org/10.1016/j.envres.2020.109208 .
Estes ML, McAllister AK. Maternal immune activation: implications for neuropsychiatric disorders. Science. 2016;353(6301):772–7. https://doi.org/10.1126/science.aag3194 .
doi: 10.1126/science.aag3194
Bölte S, Girdler S, Marschik PB. The contribution of environmental exposure to the etiology of autism spectrum disorder. Cell Mol Life Sci. 2019;76(7):1275–97. https://doi.org/10.1007/s00018-018-2988-4 .
doi: 10.1007/s00018-018-2988-4
Heyer DB, Meredith RM. Environmental toxicology: sensitive periods of development and neurodevelopmental disorders. Neurotoxicology. 2017;58:23–41. https://doi.org/10.1016/j.neuro.2016.10.017 .
doi: 10.1016/j.neuro.2016.10.017
Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int J Epidemiol. 2014;43(2):443–64. https://doi.org/10.1093/ije/dyt282 .
doi: 10.1093/ije/dyt282
Doherty BT, Romano ME, Gui J, et al. Periconceptional and prenatal exposure to metal mixtures in relation to behavioral development at 3 years of age. Environ Epidemiol. 2020;4(4). https://doi.org/10.1097/EE9.0000000000000106 .
Fruh V, Rifas-Shiman SL, Amarasiriwardena C, et al. Prenatal lead exposure and childhood executive function and behavioral difficulties in project viva. Neurotoxicology. 2019;75(May):105–15. https://doi.org/10.1016/j.neuro.2019.09.006 .
doi: 10.1016/j.neuro.2019.09.006
Jedynak P, Maitre L, Guxens M, et al. Prenatal exposure to a wide range of environmental chemicals and child behaviour between 3 and 7 years of age – an exposome-based approach in 5 European cohorts. Sci Total Environ. 2021;763(December 2020):144115. https://doi.org/10.1016/j.scitotenv.2020
doi: 10.1016/j.scitotenv.2020
Austin C, Curtin P, Arora M, et al. Elemental dynamics in hair accurately predict future autism spectrum disorder diagnosis: an international multi-center study. J Clin Med. 2022;11(23):7154. https://doi.org/10.3390/jcm11237154
doi: 10.3390/jcm11237154
Skogheim TS, Weyde KVF, Engel SM, et al. Metal and essential element concentrations during pregnancy and associations with autism spectrum disorder and attention-deficit/hyperactivity disorder in children. Environ Int. 2021;152(October 2020):106468.
doi: 10.1136/openhrt-2015-000290
Chung MK, House JS, Akhtari FS, et al. Decoding the exposome: data science methodologies and implications in exposome-wide association studies (ExWASs). Exposome. 2024;4(1). https://doi.org/10.1093/exposome/osae001
doi: 10.1093/exposome/osae001
Zheng Y, Chen Z, Pearson T, Zhao J, Hu H, Prosperi M. Design and methodology challenges of environment-wide association studies: a systematic review. Environ Res. 2020;183:109275. https://doi.org/10.1016/j.envres.2020.109275
doi: 10.1016/j.envres.2020.109275
Newschaffer CJ, Croen LA, Fallin MD, et al. Infant siblings and the investigation of autism risk factors. J Neurodev Disord. 2012;4(1):7. https://doi.org/10.1186/1866-1955-4-7
doi: 10.1186/1866-1955-4-7
Hertz-Picciotto I, Schmidt RJ, Walker CK, et al. A prospective study of environmental exposures and early biomarkers in autism spectrum disorder: design, protocols, and preliminary data from the MARBLES study. Environ Health Perspect. 126(11):117004. https://doi.org/10.1289/EHP535 .
Hansen SN, Schendel DE, Francis RW, et al. Recurrence risk of autism in siblings and cousins: a multi-national, population-based study. J Am Acad Child Adolesc Psychiatry. 2019;58(9):866–75. https://doi.org/10.1016/j.jaac.2018.11.017 .
doi: 10.1016/j.jaac.2018.11.017
Miller M, Musser ED, Young GS, Olson B, Steiner RD, Nigg JT. Sibling recurrence risk and cross-aggregation of attention-deficit/hyperactivity disorder and autism spectrum disorder. JAMA Pediatr. 2019;173(2):147–52. https://doi.org/10.1001/jamapediatrics.2018.4076 .
doi: 10.1001/jamapediatrics.2018.4076
Ozonoff S, Young GS, Belding A, et al. The broader autism phenotype in infancy: when does it emerge? J Am Acad Child Adolesc Psychiatry. 2014;53(4):398-407.e2. https://doi.org/10.1016/j.jaac.2013.12.020 .
doi: 10.1016/j.jaac.2013.12.020
Mordaunt CE, Park BY, Bakulski KM, et al. A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood. Mol Autism. 2019;10:36. https://doi.org/10.1186/s13229-019-0287-z .
doi: 10.1186/s13229-019-0287-z
Philippat C, Barkoski J, Tancredi DJ, et al. Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort. Int J Hyg Environ Health. 2018;221(3):548–55. https://doi.org/10.1016/j.ijheh.2018.02.004 .
doi: 10.1016/j.ijheh.2018.02.004
Martinez-Morata I, Sobel M, Tellez-Plaza M, Navas-Acien A, Howe CG, Sanchez TR. A state-of-the-science review on metal biomarkers. Curr Environ Health Rep. 2023;10(3):215–49. https://doi.org/10.1007/s40572-023-00402-x .
doi: 10.1007/s40572-023-00402-x
Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg. 1990;5(1):46–51. https://doi.org/10.1080/1047322X.1990.10389587 .
doi: 10.1080/1047322X.1990.10389587
Middleton DRS, Watts MJ, Polya DA. A comparative assessment of dilution correction methods for spot urinary analyte concentrations in a UK population exposed to arsenic in drinking water. Environ Int. 2019;130:104721. https://doi.org/10.1016/j.envint.2019.03.069
doi: 10.1016/j.envint.2019.03.069
Muller CJ, MacLehose RF. Estimating predicted probabilities from logistic regression: different methods correspond to different target populations. Int J Epidemiol. 2014;43(3):962–70. https://doi.org/10.1093/ije/dyu029 .
doi: 10.1093/ije/dyu029
Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019;22(4):153–60. https://doi.org/10.1136/ebmental-2019-300117 .
doi: 10.1136/ebmental-2019-300117
Campbell KA, Hickman R, Fallin MD, Bakulski KM. Prenatal exposure to metals and autism spectrum disorder: current status and future directions. Curr Opin Toxicol. 2021;26:39–48. https://doi.org/10.1016/j.cotox.2021.04.001 .
doi: 10.1016/j.cotox.2021.04.001
Weisskopf MG, Kioumourtzoglou MA, Roberts AL. Air pollution and autism spectrum disorders: causal or confounded? Curr Environ Health Rep. 2015;2(4):430–9. https://doi.org/10.1007/s40572-015-0073-9 .
doi: 10.1007/s40572-015-0073-9
Yu X, Mostafijur Rahman M, Carter SA, et al. Prenatal air pollution, maternal immune activation, and autism spectrum disorder. Environ Int. 2023;179:108148. https://doi.org/10.1016/j.envint.2023.108148
doi: 10.1016/j.envint.2023.108148
Amegah AK, Sewor C, Jaakkola JJK. Cadmium exposure and risk of adverse pregnancy and birth outcomes: a systematic review and dose–response meta-analysis of cohort and cohort-based case–control studies. J Expo Sci Environ Epidemiol. 2021;31(2):299–317. https://doi.org/10.1038/s41370-021-00289-6 .
doi: 10.1038/s41370-021-00289-6
Geng HX, Wang L. Cadmium: toxic effects on placental and embryonic development. Environ Toxicol Pharmacol. 2019;67:102–7. https://doi.org/10.1016/j.etap.2019.02.006 .
doi: 10.1016/j.etap.2019.02.006
ATSDR. Toxicological Profile for Cesium. Atlanta: Agency for Toxic Substances and Disease Registry (US); 2004.
Issah I, Duah MS, Arko-Mensah J, Bawua SA, Agyekum TP, Fobil JN. Exposure to metal mixtures and adverse pregnancy and birth outcomes: a systematic review. Sci Total Environ. 2024;908:168380. https://doi.org/10.1016/j.scitotenv.2023.168380
doi: 10.1016/j.scitotenv.2023.168380
Adams J, Howsmon DP, Kruger U, et al. Significant association of urinary toxic metals and autism-related symptoms—a nonlinear statistical analysis with cross validation. PLoS One. 2017;12(1):e0169526. https://doi.org/10.1371/journal.pone.0169526
doi: 10.1371/journal.pone.0169526
Chen X, Huang L, Li Q, et al. Effect of maternal thallium exposure in early pregnancy on the risk of preterm birth. Environ Sci Pollut Res. 2022;29(33):49966–75. https://doi.org/10.1007/s11356-022-19332-6 .
doi: 10.1007/s11356-022-19332-6
Nakhaee S, Amirabadizadeh A, Farnia V, Ali Azadi N, Mansouri B, Radmehr F. Association between biological lead concentrations and Autism Spectrum Disorder (ASD) in children: a systematic review and meta-analysis. Biol Trace Elem Res. 2023;201(4):1567–81. https://doi.org/10.1007/s12011-022-03265-9 .
doi: 10.1007/s12011-022-03265-9
ATSDR. Toxicological Profile for Lead. Atlanta: Agency for Toxic Substances and Disease Registry (US); 2020.
Wu H, Zhao G, Liu S, et al. Supplementation with selenium attenuates autism-like behaviors and improves oxidative stress, inflammation and related gene expression in an autism disease model. J Nutr Biochem. 2022;107:109034. https://doi.org/10.1016/j.jnutbio.2022.109034
doi: 10.1016/j.jnutbio.2022.109034
El-Ansary A, Bjørklund G, Tinkov AA, Skalny AV, Al DH. Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children. Metab Brain Dis. 2017;32(4):1073–80. https://doi.org/10.1007/s11011-017-9996-1 .
doi: 10.1007/s11011-017-9996-1
Wu J, Wang D, Yan L, et al. Associations of essential element serum concentrations with autism spectrum disorder. Environ Sci Pollut Res Int. 2022;29(59):88962–71. https://doi.org/10.1007/s11356-022-21978-1 .
doi: 10.1007/s11356-022-21978-1
Guo X, Tang P, Hou C, Li R. Mendelian randomization investigation highlights different roles of selenium status in mental disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2023;122:110694. https://doi.org/10.1016/j.pnpbp.2022.110694
doi: 10.1016/j.pnpbp.2022.110694
Lee ASE, Ji Y, Raghavan R, et al. Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: a prospective birth cohort study. Autism Res. 2021;14(12):2533–43. https://doi.org/10.1002/aur.2617 .
doi: 10.1002/aur.2617
Lin PD, Cardenas A, Rifas-Shiman SL, et al. Diet and erythrocyte metal concentrations in early pregnancy—cross-sectional analysis in project viva. Am J Clin Nutr. 2021;114(2):540–9. https://doi.org/10.1093/ajcn/nqab088 .
doi: 10.1093/ajcn/nqab088
Yu L, Liu W, Wang X, et al. A review of practical statistical methods used in epidemiological studies to estimate the health effects of multi-pollutant mixture. Environ Pollut. 2022;306:119356. https://doi.org/10.1016/j.envpol.2022.119356
doi: 10.1016/j.envpol.2022.119356
Yu EX, Dou JF, Volk HE, et al. Prenatal metal exposures and child social responsiveness scale scores in 2 prospective studies. Environ Health Insights. 2024;18:11786302231225312. https://doi.org/10.1177/11786302231225313 .
doi: 10.1177/11786302231225313
ATSDR. Toxicological Profile for Cadmium. Atlanta: Agency for Toxic Substances and Disease Registry (US); 2012.
Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metals toxicity and the environment. EXS. 2012;101:133–64. https://doi.org/10.1007/978-3-7643-8340-4_6 .
doi: 10.1007/978-3-7643-8340-4_6