Prenatal exposure to multiple endocrine-disrupting chemicals and childhood BMI trajectories in the INMA cohort study

Background: Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. Objective: The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. Methods: Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (n = 1,911), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. Results: In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE concentration = 1.19 (95% CI: 1.05, 1.35); RRR for PFNA = 1.32 (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the mixture =1.70; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. Discussion: This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.This study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 874583, the ATHLETE (Advancing Tools for Human Early Lifecourse Exposome Research and Translation) project, and grant agreement no. 825712, the OBERON project (both to M.V.). M.C. and M.G. hold Miguel Servet fellowships (MS16/00128, CPII18/00018, to M.C.) funded by Instituto de Salud Carlos III and co-funded by the European Social Fund “Investing in Your Future.” Instituto de Salud Global de Barcelona (ISGlobal) acknowledges support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. INMA Gipuzkoa: This study was funded by grants from the Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090, FIS-PI13/02187, and FIS-PI18/01142, including FEDER funds), Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Department of Health of the Basque Government (2005111093, 2009111069, 2013111089, and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001, and DFG15/221), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). INMA Valencia: This study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), and the Alicia Koplowitz Foundation 2017. INMA Sabadell: This study was funded by grants from the Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151, including FEDER funds; PI12/01890, including FEDER funds; CP13/00054, including FEDER funds; PI15/00118, including FEDER funds; CP16/00128, including FEDER funds; PI16/00118, including FEDER funds; PI16/00261, including FEDER funds; PI17/01340, including FEDER funds; PI18/00547, including FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241 (to P.M.), Generalitat de Catalunya-AGAUR (2009 SGR 501 and 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991, including FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010; EST-2016 RF-21), EU Commission (261357, 308333, 603794, and 634453)