Maternal hypomagnesemia causes placental abnormalities and fetal and postnatal mortality

Abstract

Introduction: Magnesium (Mg2þ) is essential for cellular growth and the maintenance of normal cellular processes. However, little is known about how maternal hypomagnesemia during pregnancy affects fetal growth and development. This study investigated the effects of maternal hypomagnesemia on the late gestation placenta and fetus, and postnatal outcomes until weaning. Methods: Female CD1 mice consumed a control (0.2% w/w Mg2þ), moderately Mg2þ deficient (MMD; 0.02% w/w Mg2þ) or severely Mg2þ deficient (SMD; 0.005% w/w Mg2þ) diet for 4 weeks prior to mating and throughout pregnancy. Dams were killed at E18.5 for embryonic studies or allowed to litter naturally and the offspring studied up to postnatal day 21. Results: At E18.5, both Mg2þ deficient diets decreased maternal plasma and bone Mg2þ but only the SMD diet decreased fetal plasma Mg2þ. Maternal hypomagnesemia led to fetal loss and fetal growth restriction. Maternal Mg2þ deficiency increased placental glycogen cell area and decreased spongiotrophoblast cell area while upregulating mRNA expression of the MagT1 Mg2þ transporter in spongiotrophoblast cells. The SMD animals also displayed instances of gross placental abnormalities. After birth, pups in the SMD group had increased early postnatal mortality and failed to thrive. Pups in the MMD group underwent catch-up growth but remained shorter than controls at PN21 and were hypomagnesemic and hypoglycemic. Conclusions: These changes suggest that maternal Mg2þ deficiency during pregnancy impairs placental development and fetal growth, which may have long-term health consequences for offspring. Collectively, these results have important implications for women who are Mg2þ deficient during pregnancy