African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards.
We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs.
First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86).
Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = −0.47, 95% CI = −1.56, 0.61) and birthweight z-scores (mean change per quartile increase = −0.49, 95% CI = −1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations.
We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs.
African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 6 print issues and online access
$259.00 per year
only $43.17 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Per Emory University Institutional Review Board approval, the data that support the findings of this study are restricted for transmission to those outside the primary investigative team. Data sharing with investigators outside the team requires IRB approval. Requests may be submitted to the Anne Dunlop, MD, MPH (firstname.lastname@example.org).
Purisch SE, Gyamfi-Bannerman C. Epidemiology of preterm birth. Semin Perinatol. 2017;41:387–91.
Malhotra A, Allison BJ, Castillo-Melendez M, Jenkin G, Polglase GR, Miller SL. Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front Endocrinol. 2019;10. https://www.frontiersin.org/article/10.3389/fendo.2019.00055.
Giscombé CL, Lobel M. Explaining disproportionately high rates of adverse birth outcomes among African Americans: the impact of stress, racism, and related factors in pregnancy. Psychol Bull. 2005;131:662–83.
Braveman P, Dominguez TP, Burke W, Dolan SM, Stevenson DK, Jackson FM et al. Explaining the black-white disparity in preterm birth: a consensus statement from a multi-disciplinary scientific work group convened by the march of dimes. Front Reproductive Health. 2021;3. https://www.frontiersin.org/article/10.3389/frph.2021.684207.
Zota AR, Shamasunder B. The environmental injustice of beauty: framing chemical exposures from beauty products as a health disparities concern. Am J Obstet Gynecol. 2017;217:418.e1–18.e6.
Chang C-J, Ryan PB, Smarr MM, Kannan K, Panuwet P, Dunlop AL, et al. Serum per- and polyfluoroalkyl substance (PFAS) concentrations and predictors of exposure among pregnant African American women in the Atlanta area, Georgia. Environ Res. 2021;198:110445.
Varshavsky JR, Sen S, Robinson JF, Smith SC, Frankenfield J, Wang Y, et al. Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation. Sci Rep. 2020;10:12247.
Wang Z, Walker GW, Muir DCG, Nagatani-Yoshida K. Toward a global understanding of chemical pollution: a first comprehensive analysis of national and regional chemical inventories. Environ Sci Technol. 2020;54:2575–84.
Calafat AM, Wong LY, Kuklenyik Z, Reidy JA, Needham LL. Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000. Environ Health Perspect. 2007;115:1596–602.
Silva Manori J, Barr Dana B, Reidy John A, Malek Nicole A, Hodge Carolyn C, Caudill Samuel P, 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;112:331–38.
Sjödin A, Jones RS, Wong L-Y, Caudill SP, Calafat AM. Polybrominated diphenyl ethers and biphenyl in serum: time trend study from the National Health and Nutrition Examination Survey for years 2005/06 through 2013/14. Environ Sci Technol. 2019;53:6018–24.
Sunderland EM, Hu XC, Dassuncao C, Tokranov AK, Wagner CC, Allen JG. A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects. J Expo Sci Environ Epidemiol. 2019;29:131–47.
Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: toxicology and exposure. Int J Hyg Environ Health. 2007;210:623–34.
Geyer HJ, Schramm K-W, Feicht E, Fried K, Henkelmann B, Lenoir D et al. Terminal elimination half-lives of the brominated flame retardants TBBPA, HBCD, and lower brominated PBDEs in humans. Organohalogen compounds: Vol. 66. DIOXIN 2004. 24th international symposium on halogenated organic pollutants and POPs (pp. 3867–72).
Jayaraj R, Megha P, Sreedev P. Review Article. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment. Interdiscip Toxicol. 2016;9:90–100.
Völkel W, Colnot T, Csanády GA, Filser JG. Dekant W. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem Res Toxicol. 2002;15:1281–87.
Buckley JP, Kuiper JR, Bennett DH, Barrett ES, Bastain T, Breton CV, et al. Exposure to contemporary and emerging chemicals in commerce among pregnant women in the United States: The Environmental influences on Child Health Outcome (ECHO) program. Environ Sci Technol. 2022;56:6560–73.
Goin DE, Abrahamsson D, Wang M, Park J-S, Sirota M, Morello-Frosch R et al. Investigating geographic differences in environmental chemical exposures in maternal and cord sera using non-targeted screening and silicone wristbands in California. J Exposure Sci Environ Epidemiol. 2022. https://doi.org/10.1038/s41370-022-00426-9.
Morello-Frosch R, Cushing LJ, Jesdale BM, Schwartz JM, Guo W, Guo T, et al. Environmental chemicals in an urban population of pregnant women and their newborns from San Francisco. Environ Sci Technol. 2016;50:12464–72.
Woodruff TJ, Zota AR, Schwartz JM. Environmental chemicals in pregnant women in the United States: NHANES 2003-2004. Environ Health Perspect. 2011;119:878–85.
Welch BM, Keil AP, Buckley JP, Calafat AM, Christenbury KE, Engel SM et al. Associations between prenatal urinary biomarkers of phthalate exposure and preterm birth: a pooled study of 16 US cohorts. JAMA Pediatrics. 2022. https://doi.org/10.1001/jamapediatrics.2022.2252.
Bommarito PA, Welch BM, Keil AP, Baker GP, Cantonwine DE, McElrath TF, et al. Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery. Environ Health. 2021;20:68.
Gao X, Ni W, Zhu S, Wu Y, Cui Y, Ma J, et al. Per- and polyfluoroalkyl substances exposure during pregnancy and adverse pregnancy and birth outcomes: A systematic review and meta-analysis. Environ Res. 2021;201:111632.
Liu Y, Xie Y, Tian Y, Liu H, He C, An S et al. Associations between polybrominated diphenyl ethers concentrations in human placenta and small for gestational age in Southwest China. Front Public Health. 2022; 10. https://doi.org/10.3389/fpubh.2022.812268.
Panagopoulos Abrahamsson D, Wang A, Jiang T, Wang M, Siddharth A, Morello-Frosch R, et al. A comprehensive non-targeted analysis study of the prenatal exposome. Environ Sci Technol. 2021;55:10542–57.
Lampa E, Eguchi A, Todaka E, Mori C. Fetal exposure markers of dioxins and dioxin-like PCBs. Environ Sci Pollut Res. 2018;25:11940–11947.
Ashrap P, Watkins DJ, Mukherjee B, Boss J, Richards MJ, Rosario Z, et al. Maternal blood metal and metalloid concentrations in association with birth outcomes in Northern Puerto Rico. Environ Int. 2020;138:105606.
Cathey AL, Eaton JL, Ashrap P, Watkins DJ, Rosario ZY, Vélez Vega C, et al. Individual and joint effects of phthalate metabolites on biomarkers of oxidative stress among pregnant women in Puerto Rico. Environ Int. 2021;154:106565.
Boss J, Zhai J, Aung MT, Ferguson KK, Johns LE, McElrath TF, et al. Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores. Environ Health. 2018;17:56.
Hu JMY, Arbuckle TE, Janssen P, Lanphear BP, Zhuang LH, Braun JM, et al. Prenatal exposure to endocrine disrupting chemical mixtures and infant birth weight: a Bayesian analysis using kernel machine regression. Environ Res. 2021;195:110749.
Kalloo G, Wellenius GA, McCandless L, Calafat AM, Sjodin A, Romano ME, et al. Exposures to chemical mixtures during pregnancy and neonatal outcomes: the HOME study. Environ Int. 2020;134:105219.
Cabrera-Rodríguez R, Luzardo OP, Almeida-González M, Boada LD, Zumbado M, Acosta-Dacal A, et al. Association between prenatal exposure to multiple persistent organic pollutants (POPs) and growth indicators in newborns. Environ Res. 2019;171:285–92.
Hwa Jung K, Pitkowsky Z, Argenio K, Quinn JW, Bruzzese J-M, Miller RL, et al. The effects of the historical practice of residential redlining in the United States on recent temporal trends of air pollution near New York City schools. Environ Int. 2022;169:107551.
Ray K. In the name of racial justice: why bioethics should care about environmental toxins. Hastings Cent Rep. 2021;51:23–6.
Corwin EJ, Hogue CJ, Pearce B, Hill CC, Read TD, Mulle J, et al. Protocol for the Emory University African American vaginal, oral, and gut microbiome in pregnancy cohort study. BMC Pregnancy Childbirth. 2017;17:161.
Brennan PA, Dunlop AL, Smith AK, Kramer M, Mulle J, Corwin EJ. Protocol for the Emory University African American maternal stress and infant gut microbiome cohort study. BMC Pediatrics. 2019;19:246.
Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg. 1990;5:46–51.
Barr Dana B, Wilder Lynn C, Caudill Samuel P, Gonzalez Amanda J, Needham Lance L, Pirkle, James L. Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005;113:192–200.
Balshaw DM, Collman GW, Gray KA, Thompson CL. The Children’s Health Exposure Analysis Resource: enabling research into the environmental influences on children’s health outcomes. Curr Opin Pediatr. 2017;29:385–9.
Honda M, Robinson M, Kannan K. A rapid method for the analysis of perfluorinated alkyl substances in serum by hybrid solid-phase extraction. Environ Chem. 2018;15:92–9.
Darrow LA, Jacobson MH, Preston EV, Lee GE, Panuwet P, Hunter RE Jr, et al. Predictors of serum polybrominated diphenyl ether (PBDE) concentrations among children aged 1–5 years. Environ Sci Technol. 2017;51:645–54.
Jacobson MH, Barr DB, Marcus M, Muir AB, Lyles RH, Howards PP, et al. Serum polybrominated diphenyl ether concentrations and thyroid function in young children. Environ Res. 2016;149:222–30.
Mutic AD, Barr DB, Hertzberg VS, Brennan PA, Dunlop AL, McCauley LA. Polybrominated diphenyl ether serum concentrations and depressive symptomatology in pregnant African American women. Int J Environ Res Public Health. 2021;18. https://doi.org/10.3390/ijerph18073614.
Marder ME, Panuwet P, Hunter RE, Ryan PB, Marcus M, Barr DB. Quantification of polybrominated and polychlorinated biphenyls in human matrices by isotope-dilution gas chromatography–tandem mass spectrometry. J Anal Toxicol. 2016;40:511–18.
Olsson AO, Baker SE, Nguyen JV, Romanoff LC, Udunka SO, Walker RD, et al. A liquid chromatography−tandem mass spectrometry multiresidue method for quantification of specific metabolites of organophosphorus pesticides, synthetic pyrethroids, selected herbicides, and DEET in human urine. Anal Chem. 2004;76:2453–61.
Zhang X, Barr DB, Dunlop AL, Panuwet P, Sarnat JA, Lee GE et al. Assessment of metabolic perturbations associated with exposure to phthalates among pregnant African American women. Sci Total Environ. 2022;818:151689.
Zhou X, Kramer JP, Calafat AM, Ye X. Automated on-line column-switching high performance liquid chromatography isotope dilution tandem mass spectrometry method for the quantification of bisphenol A, bisphenol F, bisphenol S, and 11 other phenols in urine. J Chromatogr B. 2014;944:152–56.
Toutenburg H, Fisher RA, Yates F. Statistical tables for biological, agricultural and medical research. 6th Ed. Oliver & Boyd, Edinburgh and London 1963. X, 146 P. Preis 42 s net. Biom Z. 1971;13:285.
Knuth DE. The art of computer programming, 2 (3rd ed.): seminumerical algorithms. USA: Addison-Wesley Longman Publishing Co., Inc.; 1997.
Yakimavets V, Qiu T, Panuwet P, D’Souza PE, Brennan PA, Dunlop AL, et al. Simultaneous quantification of urinary tobacco and marijuana metabolites using solid-supported liquid-liquid extraction coupled with liquid chromatography tandem mass spectrometry. J Chromatogr B. 2022;1208:123378.
Committee Opinion No 700: methods for estimating the due date. Obstet Gynecol. 2017;129. https://journals.lww.com/greenjournal/Fulltext/2017/05000/Committee_Opinion_No_700__Methods_for_Estimating.50.aspx.
Aris IM, Kleinman KP, Belfort MB, Kaimal A, Oken E. A 2017 US reference for singleton birth weight percentiles using obstetric estimates of gestation. Pediatrics. 2019;144:e20190076.
Keil AP, Buckley JP, O’Brien KM, Ferguson KK, Zhao S, White AJ. A quantile-based g-computation approach to addressing the effects of exposure mixtures. Environ Health Perspect. 2020;128:47004.
Bobb JF, Claus Henn B, Valeri L, Coull BA. Statistical software for analyzing the health effects of multiple concurrent exposures via Bayesian kernel machine regression. Environ Health. 2018;17:67.
Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, et al. Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics. 2015;16:493–508.
Darbre PD. Chapter 15 - Endocrine disruption and disorders of energy metabolism. In: Darbre PD, editor. Endocrine disruption and human health. Boston: Academic Press; 2015, pp 273–85.
Eick SM, Hom Thepaksorn EK, Izano MA, Cushing LJ, Wang Y, Smith SC, et al. Associations between prenatal maternal exposure to per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) and birth outcomes among pregnant women in San Francisco. Environ Health. 2020;19:100.
Harley KG, Chevrier J, Schall RA, Sjödin A, Bradman A, Eskenazi B. Association of prenatal exposure to polybrominated diphenyl ethers and infant birth weight. Am J Epidemiol. 2011;174:885–92.
Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, et al. Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environ Health Perspect. 2004;112:1116–24.
Zhong Q, Liu H, Fu H, Niu Q, Wu H, Huang F. Prenatal exposure to phthalates with preterm birth and gestational age: a systematic review and meta-analysis. Chemosphere. 2021;282:130991.
Ferguson KK, McElrath TF, Meeker JD. Environmental phthalate exposure and preterm birth. JAMA Pediatrics. 2014;168:61–7.
Ferguson KK, Rosen EM, Barrett ES, Nguyen RHN, Bush N, McElrath TF, et al. Joint impact of phthalate exposure and stressful life events in pregnancy on preterm birth. Environ Int. 2019;133:105254.
Santos S, Sol CM, van Zwol – Janssens C, Philips EM, Asimakopoulos AG, Martinez-Moral M-P, et al. Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study. Environ Int. 2021;151:106443.
Namat A, Xia W, Xiong C, Xu S, Wu C, Wang A, et al. Association of BPA exposure during pregnancy with risk of preterm birth and changes in gestational age: a meta-analysis and systematic review. Ecotoxicol Environ Saf. 2021;220:112400.
Deji Z, Liu P, Wang X, Zhang X, Luo Y, Huang Z. Association between maternal exposure to perfluoroalkyl and polyfluoroalkyl substances and risks of adverse pregnancy outcomes: a systematic review and meta-analysis. Sci Total Environ. 2021;783:146984.
Peltier MR, Fassett MJ, Arita Y, Chiu VY, Shi JM, Takhar HS, et al. Women with high plasma levels of PBDE-47 are at increased risk of preterm birth. J Perinat Med. 2021;49:439–47.
Bell GA, Perkins N, Buck Louis GM, Kannan K, Bell EM, Gao C et al. Exposure to persistent organic pollutants and birth characteristics: the upstate KIDS study. Epidemiology. 2019; 30. https://journals.lww.com/epidem/Fulltext/2019/11001/Exposure_to_Persistent_Organic_Pollutants_and.13.aspx.
Naksen W, Prapamontol T, Mangklabruks A, Chantara S, Thavornyutikarn P, Srinual N, et al. Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand. Environ Res. 2015;142:288–96.
Ouidir M, Buck Louis GM, Kanner J, Grantz KL, Zhang C, Sundaram R, et al. Association of maternal exposure to persistent organic pollutants in early pregnancy with fetal growth. JAMA Pediatrics. 2020;174:149–61.
Zhang Y, Mustieles V, Williams PL, Wylie BJ, Souter I, Calafat AM, et al. Parental preconception exposure to phenol and phthalate mixtures and the risk of preterm birth. Environ Int. 2021;151:106440.
Lazarevic N, Barnett AG, Sly PD, Callan AC, Stasinska A, Heyworth JS, et al. Prenatal exposure to mixtures of persistent environmental chemicals and fetal growth outcomes in Western Australia. Int J Hyg Environ Health. 2022;240:113899.
Bell ML, Ebisu K. Environmental inequality in exposures to airborne particulate matter components in the United States. Environ Health Perspect. 2012;120:1699–704.
James-Todd T, Senie R, Terry MB. Racial/Ethnic differences in hormonally-active hair product use: a plausible risk factor for health disparities. J Immigr Minority Health. 2012;14:506–11.
Schisterman EF, Whitcomb BW, Buck LGM, Louis TA. Lipid adjustment in the analysis of environmental contaminants and human health risks. Environ Health Perspect. 2005;113:853–57.
We would like to thank all the study participants who participated in this study, and the clinical health care providers and staff at the prenatal recruiting sites for helping with data and sample collection and logistics and sample chemical analyses in the laboratory, especially Nathan Mutic, Estefani Ignacio Gallegos, Nikolay Patrushev, Kristi Maxwell Logue, Castalia Thorne, Shirleta Reid, and Cassandra Hall. We would also like to thank Che-Jung Chang for her assistance with data analysis. This work was supported by the National Institute of Health (NIH) research grants [R01NR014800, R01MD009064, R24ES029490, R01MD009746, R21ES032117], NIH Center Grants [P50ES026071, P30ES019776, UH3OD023318, U2CES026560, U2CES026542, U2COD023375], and Environmental Protection Agency (USEPA) center grant . Funding for Stephanie M. Eick was additionally provided from the JPB Environmental Health Fellowship.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Eick, S.M., Tan, Y., Taibl, K.R. et al. Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort. J Expo Sci Environ Epidemiol (2023). https://doi.org/10.1038/s41370-023-00530-4
- Exposure assessment