Environmental Toxicant Exposure and Hypertensive Disorders of Pregnancy: Recent Findings
Purpose of Review
To assess the strength of evidence for associations between environmental toxicants and hypertensive disorders of pregnancy, suggest potential biological mechanisms based on animal and in vitro studies, and highlight avenues for future research.
Evidence is strongest for links between persistent chemicals, including lead, cadmium, organochlorine pesticides, and polycyclic biphenyls, and preeclampsia, although associations are sometimes not detectable at low-exposure levels. Results have been inconclusive for bisphenols, phthalates, and organophosphates. Biological pathways may include oxidative stress, epigenetic changes, endocrine disruption, and abnormal placental vascularization. Additional prospective epidemiologic studies beginning in the preconception period and extending postpartum are needed to assess the life course trajectory of environmental exposures and women’s reproductive and cardiovascular health. Future studies should also consider interactions between chemicals and consider nonlinear associations.
These results confirm recommendations by the International Federation of Gynecology and Obstetrics, the American Society for Reproductive Medicine, the American Academy of Pediatrics, and the Endocrine Society that providers counsel their pregnant patients to limit exposure to environmental toxicants.
KeywordsEndocrine disruptors Environmental exposures Heavy metals Pesticides Bisphenol A Preeclampsia Gestational hypertension
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 6.Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2)Google Scholar
- 8.Stuart JJ, Tanz LJ, Missmer SA, Rimm EB, Spiegelman D, James-Todd TM, Rich-Edwards JW. Hypertensive disorders of pregnancy and maternal cardiovascular disease risk factor development: an observational cohort study. Ann Intern Med 2018.Google Scholar
- 9.Centers for Disease Control and Prevention. Data on selected pregnancy complications in the United States. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregnancy-complications-data.htm Accessed 5/23/2018.
- 10.Centers for Disease Control and Prevention. Pregnancy mortality surveillance system. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pmss.html Accessed 5/23/2018.
- 16.Roman HA, Walsh TL, Coull BA, Dewailly E, Guallar E, Hattis D, et al. Evaluation of the cardiovascular effects of methylmercury exposures: current evidence supports development of a dose-response function for regulatory benefits analysis. Environ Health Perspect. 2011;119(5):607–14.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Vena J, Boffetta P, Becher H, Benn T, Bueno-de-Mesquita HB, Coggon D, et al. Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers. Environ Health Perspect. 1998;106(Suppl 2):645–53.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Agency for Toxic Substances and Disease Registry (ATSDR). The priority list of hazardous substances. Atlanta, GA: US Department of Health and Human Services, Public Health Service, 2011.Google Scholar
- 37.•Elongi Moyene JP, Scheers H, Tandu-Umba B, Haufroid V, Buassa-Bu-Tsumbu B, Verdonck F, et al. Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo. Environ Health. 2016;15:48. This study, which measured chemicals via 24-hour urine collection, was conducted in a region with high rates of both heavy metal exposure and preeclampsia. CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Wang F, Fan F, Wang L, Ye W, Zhang Q, Xie S. Maternal cadmium levels during pregnancy and the relationship with preeclampsia and fetal biometric parameters. Biol Trace Elem Res 2018.Google Scholar
- 49.Brooks SA, Martin E, Smeester L, Grace MR, Boggess K, Fry RC. miRNAs as common regulators of the transforming growth factor (TGF)-beta pathway in the preeclamptic placenta and cadmium-treated trophoblasts: Links between the environment, the epigenome and preeclampsia. Food Chem Toxicol. 2016;98(Pt A):50–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 52.•El-Badry A, Rezk M, El-Sayed H. Mercury-induced oxidative stress may adversely affect pregnancy outcome among dental staff: a cohort study. Int J Occup Environ Med. 2018;9(3):113–9. This first-ever occupational study of mercury exposure found increased odds of preeclampsia among dental staff compared to administrative controls and identified oxidative stress as a potential mechanism. CrossRefPubMedGoogle Scholar
- 54.Toichuev RM, Zhilova LV, Paizildaev TR, Khametova MS, Rakhmatillaev A, Sakibaev KS, Madykova ZA, Toichueva AU, Schlumpf M, Weber R, Lichtensteiger W. Organochlorine pesticides in placenta in Kyrgyzstan and the effect on pregnancy, childbirth, and newborn health. Environ Sci Pollut Res Int 2017.Google Scholar
- 55.•Murray J, Eskenazi B, Bornman R, Gaspar FW, Crause M, Obida M, et al. Exposure to DDT and hypertensive disorders of pregnancy among South African women from an indoor residual spraying region: the VHEMBE study. Environ Res. 2018;162:49–54. This is the only study of HDP to be conducted in a country currently using DDT. CrossRefPubMedGoogle Scholar
- 56.•Smarr MM, Grantz KL, Zhang C, Sundaram R, Maisog JM, Barr DB, et al. Persistent organic pollutants and pregnancy complications. Sci Total Environ. 2016;551-552:285–91. This study used preconception measures of POPs and attempted to adjust for co-exposure to multiple toxicants from the same chemical class. CrossRefPubMedGoogle Scholar
- 64.•Cantonwine DE, Meeker JD, Ferguson KK, Mukherjee B, Hauser R, McElrath TF. Urinary concentrations of bisphenol A and phthalate metabolites measured during pregnancy and risk of preeclampsia. Environ Health Perspect. 2016;124(10):1651–5. This nested case-control study found that associations of urinary BPA and phthalate levels with preeclampsia varied by infant sex. CrossRefPubMedPubMedCentralGoogle Scholar
- 65.•Ye Y, Zhou Q, Feng L, Wu J, Xiong Y, Li X. Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study. Eur J Public Health. 2017;27(6):1102–7. This nested case-control study differentiated among subcategories of preeclampsia, including early- and late-onset, as well as mild and severe. CrossRefPubMedPubMedCentralGoogle Scholar
- 69.De Felice B, Manfellotto F, Palumbo A, Troisi J, Zullo F, Di Carlo C, et al. Genome-wide microRNA expression profiling in placentas from pregnant women exposed to BPA. BMC Med Genet. 2015;8:56.Google Scholar
- 74.•Ferguson KK, McElrath TF, Cantonwine DE, Mukherjee B, Meeker JD. Phthalate metabolites and bisphenol-A in association with circulating angiogenic biomarkers across pregnancy. Placenta. 2015;36(6):699–703. This study examined a potential biological mechanism by which nonpersistent chemicals may dysregulate placental development. CrossRefPubMedPubMedCentralGoogle Scholar
- 86.Exposure to toxic environmental agents. Committee Opinion No. 575. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:931–5.Google Scholar
- 88.Trasande L, Shaffer RM, Sathyanarayana S. Food additives and child health. Pediatrics 2018.Google Scholar