Tiange Liu1, Mingyu Zhang2, Mohammad L Rahman3, Xiaobin Wang4, Stefanie N Hinkle5, Cuilin Zhang6, Noel T Mueller7. 1. Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 2. Department of Epidemiology, Johns Hopkins Bloomberg of School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA. 3. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. 4. Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of General Pediatrics & Adolescent Medicine, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. 5. Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. 6. Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: zhangcu@mail.nih.gov. 7. Department of Epidemiology, Johns Hopkins Bloomberg of School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA. Electronic address: noeltmueller@jhu.edu.
Abstract
BACKGROUND: While several heavy metals and trace minerals have been linked with hypertensive disorders during pregnancy (HDP) in women, no studies have estimated the relationship of exposure to these chemicals, both independently and as a mixture, with systolic blood pressure (SBP) or diastolic blood pressure (DBP) over gestation. OBJECTIVES: We examined individual and joint effects of 1st trimester chemicals with SBP and DBP over gestation, and whether those chemicals were associated with HDP. METHODS: We used data from 1832 non-obese pregnant women with low-risk antenatal profiles from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singleton cohort (2009-2013). In plasma collected from women at 8-13 weeks' gestation (baseline enrollment), we measured heavy metals, barium (Ba), cesium (Cs), antimony (Sb), as well as trace minerals, cobalt (Co), copper (Cu), molybdenum (Mo), selenium (Se), and zinc (Zn). We obtained BP at baseline and throughout gestation until delivery and diagnosis of HDP from medical records. We used Bayesian Kernel Machine Regression (BKMR) as well as traditional linear and logistic regressions to examine the cross-sectional associations of chemicals with baseline BP and HDP. We used linear mixed effect regression to examine longitudinal associations between chemicals and rate of weekly change in BP in each trimester. We adjusted for sociodemographic and lifestyle factors and pre-pregnancy body mass index in all models. RESULTS: BKMR revealed that comparing the entire chemical mixture at the 90th percentile vs. the 50th percentile was associated with a 1.61 mmHg (95% CI: 0.41, 2.81) higher SBP and a 1.09 mmHg (0.10, 2.09) higher DBP. No interactions were observed between chemicals. Accounting for chemical co-exposure in BKMR, each interquartile range (IQR) increment in Cu was associated with a 0.67 mmHg (0.02, 1.32) higher SBP and a 0.60 mmHg (0.08, 1.12) higher DBP at baseline; each IQR increment in Se was associated with a 0.67 mmHg (0.05, 1.29) higher SBP but not DBP. In longitudinal analyses, women with higher (i.e., above median concentration) baseline Cu had a 0.09 mmHg (0.01, 0.17) and 0.06 mmHg (0.001, 0.12) larger weekly decrease in SBP and DBP in 2nd trimester, respectively. Women with higher baseline Ba had a 0.12 mmHg (0.04, 0.20) larger weekly increase in SBP in 2nd trimester, while women with higher Cs had a 0.05 mmHg (0.01, 0.10) larger weekly increase in DBP in 3rd trimester. None of the chemicals examined were significantly associated with HDP. CONCLUSIONS: In this multi-ethnic cohort of women with low antenatal risk, plasma metals and trace minerals in early pregnancy, both individually and as a mixture, were statistically significantly associated with BP during gestation in small magnitude and in different directions, but not with HDP. The implications of these findings for women's postpartum BP and future cardiovascular health remains to be investigated.
BACKGROUND: While several heavy metals and trace minerals have been linked with hypertensive disorders during pregnancy (HDP) in women, no studies have estimated the relationship of exposure to these chemicals, both independently and as a mixture, with systolic blood pressure (SBP) or diastolic blood pressure (DBP) over gestation. OBJECTIVES: We examined individual and joint effects of 1st trimester chemicals with SBP and DBP over gestation, and whether those chemicals were associated with HDP. METHODS: We used data from 1832 non-obese pregnant women with low-risk antenatal profiles from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singleton cohort (2009-2013). In plasma collected from women at 8-13 weeks' gestation (baseline enrollment), we measured heavy metals, barium (Ba), cesium (Cs), antimony (Sb), as well as trace minerals, cobalt (Co), copper (Cu), molybdenum (Mo), selenium (Se), and zinc (Zn). We obtained BP at baseline and throughout gestation until delivery and diagnosis of HDP from medical records. We used Bayesian Kernel Machine Regression (BKMR) as well as traditional linear and logistic regressions to examine the cross-sectional associations of chemicals with baseline BP and HDP. We used linear mixed effect regression to examine longitudinal associations between chemicals and rate of weekly change in BP in each trimester. We adjusted for sociodemographic and lifestyle factors and pre-pregnancy body mass index in all models. RESULTS: BKMR revealed that comparing the entire chemical mixture at the 90th percentile vs. the 50th percentile was associated with a 1.61 mmHg (95% CI: 0.41, 2.81) higher SBP and a 1.09 mmHg (0.10, 2.09) higher DBP. No interactions were observed between chemicals. Accounting for chemical co-exposure in BKMR, each interquartile range (IQR) increment in Cu was associated with a 0.67 mmHg (0.02, 1.32) higher SBP and a 0.60 mmHg (0.08, 1.12) higher DBP at baseline; each IQR increment in Se was associated with a 0.67 mmHg (0.05, 1.29) higher SBP but not DBP. In longitudinal analyses, women with higher (i.e., above median concentration) baseline Cu had a 0.09 mmHg (0.01, 0.17) and 0.06 mmHg (0.001, 0.12) larger weekly decrease in SBP and DBP in 2nd trimester, respectively. Women with higher baseline Ba had a 0.12 mmHg (0.04, 0.20) larger weekly increase in SBP in 2nd trimester, while women with higher Cs had a 0.05 mmHg (0.01, 0.10) larger weekly increase in DBP in 3rd trimester. None of the chemicals examined were significantly associated with HDP. CONCLUSIONS: In this multi-ethnic cohort of women with low antenatal risk, plasma metals and trace minerals in early pregnancy, both individually and as a mixture, were statistically significantly associated with BP during gestation in small magnitude and in different directions, but not with HDP. The implications of these findings for women's postpartum BP and future cardiovascular health remains to be investigated.