Latent classes for chemical mixtures analyses in epidemiology: an example using phthalate and phenol exposure biomarkers in pregnant women

Latent classes for chemical mixtures analyses in epidemiology: an example using phthalate and phenol exposure biomarkers in pregnant women

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ABSTRACT Latent class analysis (LCA), although minimally applied to the statistical analysis of mixtures, may serve as a useful tool for identifying individuals with shared real-life


profiles of chemical exposures. Knowledge of these groupings and their risk of adverse outcomes has the potential to inform targeted public health prevention strategies. This example applies


LCA to identify clusters of pregnant women from a case–control study within the LIFECODES birth cohort with shared exposure patterns across a panel of urinary phthalate metabolites and


parabens, and to evaluate the association between cluster membership and urinary oxidative stress biomarkers. LCA identified individuals with: “low exposure,” “low phthalates, high


parabens,” “high phthalates, low parabens,” and “high exposure.” Class membership was associated with several demographic characteristics. Compared with “low exposure,” women classified as


having “high exposure” had elevated urinary concentrations of the oxidative stress biomarkers 8-hydroxydeoxyguanosine (19% higher, 95% confidence interval [CI] = 7, 32%) and 8-isoprostane


(31% higher, 95% CI = −5, 64%). However, contrast examinations indicated that associations between oxidative stress biomarkers and “high exposure” were not statistically different from those


with “high phthalates, low parabens” suggesting a minimal effect of higher paraben exposure in the presence of high phthalates. The presented example offers verification of latent class


assignments through application to an additional data set as well as a comparison to another unsupervised clustering approach, k-means clustering. LCA may be more easily implemented, more


consistent, and more able to provide interpretable output. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS


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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PRENATAL EXPOSURE TO PERSISTENT AND NON-PERSISTENT CHEMICAL MIXTURES AND


ASSOCIATIONS WITH ADVERSE BIRTH OUTCOMES IN THE ATLANTA AFRICAN AMERICAN MATERNAL-CHILD COHORT Article 25 February 2023 APPLICATIONS OF MIXTURE METHODS IN EPIDEMIOLOGICAL STUDIES


INVESTIGATING THE HEALTH IMPACT OF PERSISTENT ORGANIC POLLUTANTS EXPOSURES: A SCOPING REVIEW Article Open access 10 September 2024 APPLICATION OF THREE STATISTICAL APPROACHES TO EXPLORE


EFFECTS OF DIETARY INTAKE OF MULTIPLE PERSISTENT ORGANIC POLLUTANTS ON ER-POSITIVE BREAST CANCER RISK IN THE FRENCH E3N COHORT Article Open access 15 January 2025 CODE AVAILABILITY


Accompanying code for the LCA methods is available at GitHub repository “LCAmix” from user “carrollrm.” This is available as an R markdown file to lead viewers through a simple example of


performing these methods. REFERENCES * Taylor KW, Joubert BR, Braun JM, Dilworth C, Gennings C, Hauser R, et al. Statistical approaches for assessing health effects of environmental chemical


mixtures in epidemiology: lessons from an innovative workshop. Environ Health Perspect. 2016;124:A227–A9. Article  Google Scholar  * Braun JM, Gennings C, Hauser R, Webster TF. What can


epidemiological studies tell us about the impact of chemical mixtures on human health? Environ Health Perspect. 2016;124:A6–9. Article  Google Scholar  * Agresti A. Other mixture models for


categorical data. In: Balding DJ, Bloomfield P, Cressie NAC, Fisher NI, Johnstone IM, Kadane JB, et al. eds. Categorical data analysis. Hoboken, NJ: Wiley; 2002. p. 538–75. Chapter  Google


Scholar  * Lazarevic N, Barnett AG, Sly PD, Knibbs LD. Statistical methodology in studies of prenatal exposure to mixtures of endocrine-disrupting chemicals: a review of existing approaches


and new alternatives. Environ Health Perspect. 2019;127:026001. Article  CAS  Google Scholar  * Kalloo G, Wellenius GA, McCandless L, Calafat AM, Sjodin A, Karagas M, et al. Profiles and


predictors of environmental chemical mixture exposure among pregnant women: the health outcomes and measures of the environment Study. Environ Sci Technol. 2018;52:10104–13. Article  CAS 


Google Scholar  * Zanobetti A, Austin E, Coull BA, Schwartz J, Koutrakis P. Health effects of multi-pollutant profiles. Environ Int. 2014;71:13–9. Article  CAS  Google Scholar  * Ferguson


KK, Cantonwine DE, McElrath TF, Mukherjee B, Meeker JD. Repeated measures analysis of associations between urinary bisphenol-A concentrations and biomarkers of inflammation and oxidative


stress in pregnancy. Reprod Toxicol. 2016;66:93–8. Article  CAS  Google Scholar  * Ferguson KK, McElrath TF, Chen YH, Mukherjee B, Meeker JD. Urinary phthalate metabolites and biomarkers of


oxidative stress in pregnant women: a repeated measures analysis. Environ Health Perspect. 2015;123:210–6. Article  CAS  Google Scholar  * McElrath TF, Lim KH, Pare E, Rich-Edwards J, Pucci


D, Troisi R, et al. Longitudinal evaluation of predictive value for preeclampsia of circulating angiogenic factors through pregnancy. Am J Obstet Gynecol. 2012;207:407 e1–7. Article  Google


Scholar  * Ferguson KK, McElrath TF, Meeker JD. Environmental phthalate exposure and preterm birth. JAMA Pediatr 2014;168:61–7. Article  Google Scholar  * Ferguson KK, Meeker JD, Cantonwine


DE, Mukherjee B, Pace GG, Weller D, et al. Environmental phenol associations with ultrasound and delivery measures of fetal growth. Environ Int. 2018;112:243–50. Article  CAS  Google Scholar


  * Ferguson KK, McElrath TF, Ko YA, Mukherjee B, Meeker JD. Variability in urinary phthalate metabolite levels across pregnancy and sensitive windows of exposure for the risk of preterm


birth. Environ Int. 2014;70:118–24. Article  Google Scholar  * Wei T, Simko V. R package “corrplot”: visualization of a correlation matrix. 0.84 ed 2017. * Linzer DA, Lewis JB. poLCA: an R


package for polytomous variable latent class analysis. J Stat Softw. 2011;42:1–29. Article  Google Scholar  * McCutcheon AL. Latent class analysis. Thousand Oaks, California: Sage


Publications; 1987. Book  Google Scholar  * Lin TH, Dayton CM. Model selection information criteria for non-nested latent class models. J Educ Behav Stat. 2016;22:249–64. Article  Google


Scholar  * Forster MR. Key concepts in model selection: performance and generalizability. J Math Psychol. 2000;44:205–31. Article  CAS  Google Scholar  * Calafat AM, Ye X, Wong LY, Bishop


AM, Needham LL. Urinary concentrations of four parabens in the U.S. population: NHANES 2005-2006. Environ Health Perspect. 2010;118:679–85. Article  CAS  Google Scholar  * Silva MJ, Barr DB,


Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES)


1999–2000. Environ Health Perspect. 2004;112:331–8. Article  CAS  Google Scholar  * Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey: Sample


design, 2007-2010. Available from: https://www.cdc.gov/nchs/data/series/sr_02/sr02_160.pdf. Accessed 16 Oct 2019. * MacQueen J ed. Some methods for classification and analysis of


multivariate observations. In: Proceedings of the fifth Berkeley symposium on mathematical statistics and probability; 1967: Oakland, CA, USA. * Brusco MJ, Shireman E, Steinley D. A


comparison of latent class, K-means, and K-median methods for clustering dichotomous data. Psychol Methods. 2017;22:563–80. Article  Google Scholar  * Leisch F. A toolbox for k-centroids


cluster analysis. J. Comput Stat. 2006;51:526–44. Article  Google Scholar  * Cohen J. A coefficient agreement for nominal scales. J Educ Psychol Meas. 1960;20:37–46. * Ferguson KK, Lan Z, Yu


Y, Mukherjee B, McElrath TF, Meeker JD. Urinary concentrations of phenols in association with biomarkers of oxidative stress in pregnancy: Assessment of effects independent of phthalates.


Env Int. 2019;131:104903. Article  CAS  Google Scholar  * Hendryx M, Luo J. Latent class analysis to model multiple chemical exposures among children. Environ Res. 2018;160:115–20. Article 


CAS  Google Scholar  * Kordas K, Ardoino G, Coffman DL, Queirolo EI, Ciccariello D, Mañay N, et al. Patterns of exposure to multiple metals and associations with neurodevelopment of


preschool children from Montevideo, Uruguay. J Environ Public Health. 2015;2015:493471. Article  Google Scholar  * Breiman L, Friedman J, Stone CJ, Olshen RA. Classification and regression


trees. Boca Raton, FL: Chapman and Hall/CRC; 1984. Google Scholar  * Papathomas M, Molitor J, Richardson S, Riboli E, Vineis P. Examining the joint effect of multiple risk factors using


exposure risk profiles: lung cancer in nonsmokers. Environ Health Perspect. 2011;119:84–91. Article  Google Scholar  * Stafoggia M, Breitner S, Hampel R, Basagana X. Statistical approaches


to address multi-pollutant mixtures and multiple exposures: the state of the science. Curr Environ Health Rep. 2017;4:481–90. Article  CAS  Google Scholar  * Zhao S, Yu Y, Yin D, He J, Liu


N, Qu J, et al. Annual and diurnal variations of gaseous and particulate pollutants in 31 provincial capital cities based on in situ air quality monitoring data from China National


Environmental Monitoring Center. Environ Int. 2016;86:92–106. Article  CAS  Google Scholar  * White AJ, Keller JP, Zhao S, Kaufman JD, Sandler DP. Air pollution, clustering of particulate


matter components and breast cancer. Cancer Epidemiol Biomark Prev. 2019;28:624.2–5. Article  Google Scholar  * Wang X, Mukherjee B, Batterman S, Harlow SD, Park SK. Urinary metals and metal


mixtures in midlife women: the Study of Women's Health Across the Nation (SWAN). Int J Hyg Environ Health. 2019;222:778–89. Article  Google Scholar  * Snowden JM, Reid CE, Tager IB.


Framing air pollution epidemiology in terms of population interventions, with applications to multipollutant modeling. Epidemiology. 2015;26:271–9. Article  Google Scholar  Download


references ACKNOWLEDGEMENTS This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institute of Health


(Z1AES103321). Additional funding was provided by NIEHS (R01ES018872 and R01ES029531). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Biostatistics and Computational Biology Branch, National


Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Rachel Carroll & Shanshan Zhao * Department of Mathematics and Statistics, University of North Carolina,


Wilmington, NC, USA Rachel Carroll * Epidemiology Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA Alexandra J.


White, Alexander P. Keil & Kelly K. Ferguson * Department of Epidemiology, University of North Carolina Gillings Global School of Public Health, Chapel Hill, NC, USA Alexander P. Keil *


Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA John D. Meeker * Division of Maternal-Fetal Medicine, Brigham and Women’s


Hospital, Harvard Medical School, Boston, MA, USA Thomas F. McElrath Authors * Rachel Carroll View author publications You can also search for this author inPubMed Google Scholar * Alexandra


J. White View author publications You can also search for this author inPubMed Google Scholar * Alexander P. Keil View author publications You can also search for this author inPubMed 


Google Scholar * John D. Meeker View author publications You can also search for this author inPubMed Google Scholar * Thomas F. McElrath View author publications You can also search for


this author inPubMed Google Scholar * Shanshan Zhao View author publications You can also search for this author inPubMed Google Scholar * Kelly K. Ferguson View author publications You can


also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Kelly K. Ferguson. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no


conflict of interest. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Carroll, R., White, A.J., Keil, A.P. _et al._ Latent


classes for chemical mixtures analyses in epidemiology: an example using phthalate and phenol exposure biomarkers in pregnant women. _J Expo Sci Environ Epidemiol_ 30, 149–159 (2020).


https://doi.org/10.1038/s41370-019-0181-y Download citation * Received: 09 April 2019 * Revised: 20 August 2019 * Accepted: 05 September 2019 * Published: 21 October 2019 * Issue Date:


January 2020 * DOI: https://doi.org/10.1038/s41370-019-0181-y SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a


shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Latent class models * Mixtures


methods * Phthalates * Phenols * Oxidative stress