Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort

Background Preeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort. Methods and Results A total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (PRs) and 95% CIs. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose–response trend for Mn (P for trend<0.001) and to some extent for Cd (P for trend=0.009) quintiles. After multivariable adjustment, a 1 SD increment in Mn was associated with 32% lower risk of developing preeclampsia (PR=0.68; 95% CI, 0.54–0.86), whereas a 1 SD increment in Cd was associated with 15% higher risk of preeclampsia (PR=1.15; 95% CI, 0.98–1.36). Null associations were observed for Se, Pb, and Hg. Conclusions Findings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.

[1]  Alison D. Gernand,et al.  Research Recommendations From the National Institutes of Health Workshop on Predicting, Preventing, and Treating Preeclampsia , 2019, Hypertension.

[2]  L. Trasande,et al.  Environmental Toxicant Exposure and Hypertensive Disorders of Pregnancy: Recent Findings , 2018, Current Hypertension Reports.

[3]  M. Rezk,et al.  Mercury-induced Oxidative Stress May Adversely Affect Pregnancy Outcome among Dental Staff: A Cohort Study , 2018, The international journal of occupational and environmental medicine.

[4]  W. H. Pearse,et al.  American College of Obstetricians and Gynecologists , 2018, Definitions.

[5]  Fengyun Fan,et al.  Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters , 2018, Biological Trace Element Research.

[6]  Xiaobo Yang,et al.  The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions , 2018, Oxidative medicine and cellular longevity.

[7]  T. Naicker,et al.  Elemental analysis of serum and hair from pre-eclamptic South African women. , 2017, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[8]  F. Thévenod,et al.  Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models , 2017, International journal of molecular sciences.

[9]  Nicola Persico,et al.  Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia , 2017, The New England journal of medicine.

[10]  J. Repke,et al.  Pitfalls With the New American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy , 2017, Clinical obstetrics and gynecology.

[11]  Qiong Zhang,et al.  Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia. , 2016, Environmental pollution.

[12]  B. Cheung,et al.  Continual Decrease in Blood Lead Level in Americans: United States National Health Nutrition and Examination Survey 1999-2014. , 2016, The American journal of medicine.

[13]  F. Hu,et al.  Association Between Maternal Prepregnancy Body Mass Index and Plasma Folate Concentrations With Child Metabolic Health. , 2016, JAMA pediatrics.

[14]  V. Haufroid,et al.  Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo , 2016, Environmental Health.

[15]  R. Fry,et al.  Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk , 2015, PloS one.

[16]  Li-sheng Liu,et al.  Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. , 2015, JAMA.

[17]  Y. Matsubara,et al.  Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia , 2015, International journal of molecular sciences.

[18]  E. Guallar,et al.  Placental transfer and concentrations of cadmium, mercury, lead, and selenium in mothers, newborns, and young children , 2014, Journal of Exposure Science and Environmental Epidemiology.

[19]  N. Al-Jameil,et al.  Analysis of serum trace elements-copper, manganese and zinc in preeclamptic pregnant women by inductively coupled plasma optical emission spectrometry: a prospective case controlled study in Riyadh, Saudi Arabia. , 2014, International journal of clinical and experimental pathology.

[20]  C. Redman,et al.  Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial , 2014, British Journal of Nutrition.

[21]  Mohammad Safiqul Islam,et al.  Comparative Study of Serum Zinc, Copper, Manganese, and Iron in Preeclamptic Pregnant Women , 2013, Biological Trace Element Research.

[22]  K. Smeets,et al.  Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)? , 2013, International journal of molecular sciences.

[23]  Tyler J. VanderWeele,et al.  On the definition of a confounder , 2013, Annals of statistics.

[24]  A. Tripathi,et al.  Physiological Changes in Hematological Parameters During Pregnancy , 2012, Indian Journal of Hematology and Blood Transfusion.

[25]  D. S. St. Clair,et al.  Manganese superoxide dismutase, MnSOD and its mimics. , 2012, Biochimica et biophysica acta.

[26]  Z. Paknahad,et al.  The relationship between nutrients intake and preeclampsia in pregnant women , 2012 .

[27]  D. Raymond,et al.  A Critical Review of Early-Onset and Late-Onset Preeclampsia , 2011, Obstetrical & gynecological survey.

[28]  Faha,et al.  Aha Guideline Effectiveness-based Guidelines for the Prevention of Cardiovascular Disease in Women—2011 Update a Guideline from the American Heart Association Executive Writing Committee Expert Panel Members Cvd Risk Assessment Table 1. Class Iii Interventions (not Useful/effective and May Be Harmfu , 2022 .

[29]  L. Vatten,et al.  Hypertension in Pregnancy and Later Cardiovascular Risk: Common Antecedents? , 2010, Circulation.

[30]  G. Ferns,et al.  Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. , 2010, Taiwanese journal of obstetrics & gynecology.

[31]  H. Randeva,et al.  Mouse models for preeclampsia: disruption of redox-regulated signaling , 2009, Reproductive biology and endocrinology : RB&E.

[32]  Anne B Wallis,et al.  Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987-2004. , 2008, American journal of hypertension.

[33]  Chung-Cheng Hsieh,et al.  Plasma Volume Expansion in Pregnancy: Implications for Biomarkers in Population Studies , 2007, Cancer Epidemiology, Biomarkers and Prevention.

[34]  Mark C Houston,et al.  The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. , 2007, Alternative therapies in health and medicine.

[35]  K. Tamilarasan,et al.  Cadmium induced endothelial dysfunction: Consequence of defective migratory pattern of endothelial cells in association with poor nitric oxide availability under cadmium challenge , 2006, Cell biology international.

[36]  K. Yokoyama,et al.  Lead and other trace metals in preeclampsia: a case-control study in Tehran, Iran. , 2006, Environmental research.

[37]  P. Rosso,et al.  Time Course of Maternal Plasma Volume and Hormonal Changes in Women With Preeclampsia or Fetal Growth Restriction , 2006, Hypertension.

[38]  Samina S Farooqi,et al.  The World Health Report 2005 - Make Every Mother and Child Count , 2005, Annals of Saudi Medicine.

[39]  J. Vanderlelie,et al.  Selenium deficiency as a model of experimental pre-eclampsia in rats. , 2004, Reproduction.

[40]  B. M. Schroeder,et al.  ACOG practice bulletin on diagnosing and managing preeclampsia and eclampsia. American College of Obstetricians and Gynecologists. , 2002, American family physician.

[41]  Tianhua Niu,et al.  Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. , 2002, JAMA.

[42]  L. Poston,et al.  Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial , 1999, The Lancet.

[43]  L. Duley Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean , 1992, British journal of obstetrics and gynaecology.

[44]  Nathan Mantel,et al.  Chi-square tests with one degree of freedom , 1963 .

[45]  B. Lanphear,et al.  Blood lead and preeclampsia: A meta‐analysis and review of implications , 2018, Environmental research.

[46]  Z. Matthews,et al.  Make every mother and child count: Key findings of the World Health Report 2005 , 2005 .

[47]  Peter P. Egeghy,et al.  Methods of Dealing with Values Below the Limit of Detection using SAS Carry , 2003 .

[48]  S Greenland,et al.  Tests for trend and dose response: misinterpretations and alternatives. , 1992, American journal of epidemiology.