Pregnancy Metal Mixtures and Blood Pressure and Hypertension in Mid-Life: A Prospective U.S. Cohort Study

The long-term associations between metal mixtures in pregnancy and women's mid-life blood pressure (BP) and hypertension remain unclear. In Project Viva (enrolled 1999-2002), we measured nonessential (arsenic, barium, cadmium, cesium, mercury, lead) and essential metals (copper, magnesium, manganese, selenium, zinc) in red blood cells, along with folate and vitamin B12 in plasma, collected during pregnancy. We measured mid-life BP from 2017 to 2021 (median age, 51.2 years). We examined associations of individual metals with BP using linear regression and with hypertension (≥130/80 mm Hg or use of antihypertensive medication) using modified Poisson regression. We used Bayesian kernel machine regression to examine the mixture effects of metals and micronutrients. The median follow-up time of the 493 women was 18.1 years (interquartile range, 17.8-18.6 years). After adjustment, a doubling of copper and manganese was associated with 0.75 (95% CI, 0.57-0.99) and 0.80 (95% CI, 0.71-0.91) times the risk of hypertension, respectively. Although higher cesium and selenium levels were associated with a slightly increased risk of hypertension, the 95% CIs were wide and crossed the null. A doubling of vitamin B12 was associated with a 3.64 (95% CI, 1.23-6.04) mm Hg lower systolic BP and a 2.52 (95% CI, 0.72-4.32) mm Hg lower diastolic BP. Bayesian kernel machine regression showed linear associations with no metal-metal or metal-micronutrient interactions. The essential metal mixture was monotonically associated with lower BP, while its association with hypertension showed threshold effects. Optimizing essential metal levels during pregnancy, particularly copper and manganese, along with vitamin B12, may protect against higher BP and hypertension in mid-life women.