Maternal blood metal concentrations are associated with C-reactive protein and cell adhesion molecules among pregnant women in Puerto Rico

Abstract

Studies have revealed a link between aberrant levels of maternal C-reactive protein (CRP) and cell adhesion molecules (CAMs) with adverse birth outcomes. Some epidemiologic studies have indicated that long-term metal exposures can modulate the levels of CRP and CAMs, but the associations between prenatal metal exposures and the levels of CRP and CAMs have yet to be studied more extensively. In this study, we assessed associations between maternal blood metal levels and CRP/CAMs among 617 pregnant women in the Puerto Rico PROTECT birth cohort.

Methods: Blood samples were collected from participants at 16-20 (visit 1) and 24-28 (visit 3) weeks gestation. We measured concentrations of 11 metals using inductively coupled plasma mass spectrometry (ICP-MS). From the blood samples, CRP and CAMs intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) were also quantified using a customized Luminex assay. Linear-mixed effects models (LMEs) were used to regress CRP and CAMs on metals and included random intercepts for study participants to account for correlated repeated outcome measures. Fetal sex and visit effects were estimated using interaction terms between metal exposure variables and fetal sex, as well as visit indicators, respectively.

Results: We observed significant positive associations between nickel and CRP (Δ: 7.04, 95% CI = 0.75, 13.73) and between lead and VCAM (Δ: 4.57, 95% CI = 1.36, 7.89). The positive associations were mainly driven by mothers carrying male fetuses. We also observed various visit-specific associations. The significant associations between metals and CRP were predominantly driven by visit 3; however, the significant associations between metals and VCAM were mainly driven by visit 1.

Conclusion: Certain maternal blood metal levels were significantly associated with CRP and CAMs and most of these associations were differentially driven by fetal sex, as well as by timing in pregnancy. Future studies should further explore metal-CRP/CAMs associations for a better understanding of the underlying mechanism of metal-induced adverse birth outcomes.

Keywords: CRP; ICAM; Puerto Rico; VCAM; inflammation; metals; pregnancy.

Figure 1.

Effect estimates and 95% confidence intervals from linear-mixed effects models for the associations between blood metals and CRP/CAMs among 617 women in PROTECT, by fetal sex. Red squares denote estimates for female fetuses (n = 294) and blue circles denote estimates for male fetuses (n = 323).

Figure 2.

Effect estimates and 95% confidence intervals from linear-mixed effects models for the associations between blood metals and CRP/CAMs among 617 women in PROTECT, by study visit. Purple squares denote estimates for visit 1 (Cd, Co, Cs, Cu, Hg, Mn, Ni, Pb, Zn n = 478; Mo, Sn n = 187) and green circles denote estimates for visit 3 (Cd, Co, Cs, Cu, Hg, Mn, Ni, Pb, Zn n = 379; Mo, Sn n = 149).