Maternal magnesium supplementation reduces intrauterine growth restriction and suppresses inflammation in a rat model

Abstract

Intrauterine growth restriction (IUGR) is associated withincreased inflammatory responses. We sought to investigate whether magnesium (Mg) attenuates inflammation and IUGR in a rat model. Pregnant Wistar rats (12 weeks, gestational day 18) were randomly assigned to 1 of 4 groups: normal diet with bilateral uterine artery ligation (BL) (n= 6) or sham surgery (SH) (n= 5); and Mg chloride (MgCl2) 1% (wt/vol) in the drinking water throughout gestation+ BL (MgBL) (n= 6) or SH (MgSH) (n= 5). Dams were euthanized 24 hours postsurgery (gestational day 19). Maternal plasma, fetal plasma (pooled), individual amniotic fluid (AF) samples, and placentas (PL) were collected and assessed from live fetal pups only (BL, n= 36; SH, n= 20; MgBL, n= 20; MgSH, n= 20). All samples were analyzed for cytokines/chemokines (interleukin [IL]-6, IL-1β, chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 2 [CCL2], and tumor necrosis factor [TNF-α] sensitivity <3 pg/mL) using a multiplex platform. Data were analyzed using Mann Whitney, analysis of variance, and Fisher exact tests. The incidence of IUGR (pup weight <10th percentile of SH) in the MgBL group was significantly lower (31%) than the BL group (86.3%) (relative risk, 0.36; 95% confidence interval, 0.2-0.6; P<.0001). BL significantly increased AF levels of IL-6, IL-1β, TNF-α (P < .05), and CCL2 (P < .001) vs SH and PL levels of IL-6, IL-1β, CCL2 andCXCL1 (P < .001), and TNF-α (P < .05) vs SH. Maternal MgCl2supplementation significantly decreased IL-1β, TNF-α, and CCL2 levels in AF and IL-1β in PL tissues of MgBL vs BL rats (P<.0001). Maternal oral MgCl2 supplementation reduced BL-induced IUGR by 64% and suppressed cytokine/chemokine levels in the AF and PL.