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• W4283205491 abstract "Vol. 130, No. 6 Science SelectionOpen AccessBisphenol A and Child Vascular Health: A Preview of Future Heart Disease Risk?is accompanied byMaternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children Silke Schmidt Silke Schmidt Search for more papers by this author Published:21 June 2022CID: 064003https://doi.org/10.1289/EHP11498AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit AbstractExposures to phthalates and bisphenols have well-documented adverse effects on reproductive health and human development.1 These endocrine-disrupting chemicals (EDCs) are also associated with obesity, hypertension, and blood vessel lesions in cross-sectional studies of adolescents and adults.2–5 It is conceivable that processes leading to such damage start early in life and may be affected by prenatal chemical exposure.6,7 A study recently published in Environmental Health Perspectives examined this question in children followed from gestation into childhood.8The authors measured phthalates and bisphenols in urine samples from 935 pregnant Generation R participants during their first, second, and third trimesters. The Generation R Study, based in Rotterdam, the Netherlands, comprises a population-based prospective cohort.9 At approximately 10 years of age, the women’s children underwent ultrasounds for two measurements of the common carotid artery: distensibility (elasticity) and intima-media thickness (the thickness between the intima and media layers of the vessel wall). Both distensibility and intima-media thickness reflect vascular health in the whole body10–12; thicker vessel walls and reduced elasticity are considered distinct but overlapping risk factors for cardiovascular disease in adulthood, such as atherosclerosis.13The intima layer of the artery (shown in black) is composed of endothelial cells, and the media layer (shown in pink) is made of smooth muscle and elastic fibers. Combined expansion (diastole) and contraction (systole) of the media layer pushes blood through the artery and controls blood pressure. In this transmission electron micrograph, the intima has accordioned due to contraction of the media. Image: © Steve Gschmeissner/Science Source.The authors analyzed the children’s vascular measurements in association with their mothers’ prenatal levels of three bisphenols [bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF)], low-molecular-weight phthalates as a group, high-molecular-weight phthalates, and three individual phthalates. They found no associations between any of the chemicals and distensibility. However, higher maternal urine concentrations of total bisphenols and of BPA alone were associated with thinner vessel walls in the children’s carotid artery. No associations were found for BPS, BPF, or any phthalate.The association of higher total bisphenol and BPA exposure with thinner—rather than thicker—vessel walls surprised the team initially but is biologically plausible, says first author Sophia Blaauwendraad. “Associations between higher BPA levels and atherosclerosis in adulthood [demonstrated in earlier studies14] could be due to oxidative stress that accelerates the formation of atherosclerotic plaques and thickens the vascular wall,” says Blaauwendraad, a physician and graduate student in epidemiology under senior coauthor Vincent Jaddoe at Rotterdam’s Erasmus University Medical Center. Fetal exposures, on the other hand, may be associated with an underdevelopment of the vasculature in childhood, the authors speculate. However, Blaauwendraad says, as yet no prospective studies have tracked intima-media thickness measures from childhood to adulthood.15Nikki Posnack, an assistant professor of pharmacology, physiology, and pediatrics at Children’s National Hospital in Washington, DC, says the study’s strengths include its large sample size and measurements of several subtypes of phthalates and bisphenols at three different time points during pregnancy. Posnack, who was not involved in the research, says, “This is a compelling study that opens up new opportunities for mechanistic follow-up studies in model systems.” Such studies could examine whether BPA disrupts development of blood vessels and alters their contractile properties,16 similar to the chemical’s disruption of hormonal regulation.According to Lars Lind, a professor of medicine at Uppsala University in Sweden, who also was not involved in the project, studying the effect of the chemicals on early vascular changes in animal models would be worthwhile and should be accompanied by replication efforts in other human birth cohorts. “Since the findings were unexpected, replication is critical to increase our faith in them,” says Lind. “But it is possible that these chemicals may have different effects at the fetal stage than later in life.”The association with total bisphenols appears to have been driven mainly by BPA; BPS and BPF were below the limit of detection in more than half the samples, possibly because they were collected in 2002–2006, when these chemicals were used less than today. However, human exposure to these BPA replacement chemicals has been increasing.17 “With that in mind,” Posnack says, “I think the study fills an important knowledge gap by exploring if exposure to any bisphenols in utero may affect subclinical indicators of vascular disease risk later in life.”Silke Schmidt, PhD, writes about science, health, and the environment from Madison, Wisconsin.References1. Metcalfe CD, Bayen S, Desrosiers M, Muñoz G, Sauvé S, Yargeau V. 2022. An introduction to the sources, fate, occurrence and effects of endocrine disrupting chemicals released into the environment. Environ Res 207:112658, PMID: 34990614, 10.1016/j.envres.2021.112658. Crossref, Medline, Google Scholar2. Lin CY, Shen FY, Lian GW, Chien KL, Sung FC, Chen PC, et al.2015. Association between levels of serum bisphenol A, a potentially harmful chemical in plastic containers, and carotid artery intima-media thickness in adolescents and young adults. 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Crossref, Medline, Google Scholar13. Lind L, Andersson J, Hansen T, Johansson L, Ahlström H. 2009. Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance, but not to endothelium-dependent vasodilation—the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Clin Physiol Funct Imaging 29(5):321–329, PMID: 19486081, 10.1111/j.1475-097X.2009.00871.x. Crossref, Medline, Google Scholar14. Dias P, Tvrdý V, Jirkovský E, Dolenc MS, Peterlin Mašič LP, Mladěnka P, et al.2022. The effects of bisphenols on the cardiovascular system. Crit Rev Toxicol 52(1):66–87, PMID: 35394415, 10.1080/10408444.2022.2046690. Crossref, Medline, Google Scholar15. Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, Jokinen E, Petropoulos A, Oberhoffer R, et al.2015. Intima media thickness measurement in children: a statement from the Association for European Paediatric Cardiology (AEPC) Working Group on Cardiovascular Prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis 238(2):380–387, PMID: 25555270, 10.1016/j.atherosclerosis.2014.12.029. Crossref, Medline, Google Scholar16. Cooper BL, Posnack NG. 2022. Characteristics of bisphenol cardiotoxicity: impaired excitability, contractility, and relaxation. Cardiovasc Toxicol 22(3):273–280, PMID: 35143014, 10.1007/s12012-022-09719-9. Crossref, Medline, Google Scholar17. Abraham A, Chakraborty P. 2020. A review on sources and health impacts of bisphenol A. Rev Environ Health 35(2):201–210, PMID: 31743105, 10.1515/reveh-2019-0034. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsRelated articlesMaternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children26 April 2022Environmental Health Perspectives Vol. 130, No. 6 June 2022Metrics About Article Metrics Publication History Manuscript received28 April 2022Manuscript accepted3 June 2022Originally published21 June 2022 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. 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