Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Abstract

Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24 -48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium.

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…However, the first-trimester rise in intestinal calcium absorption precedes the more marked increase in calcitriol and free calcitriol during the third trimester, which may indicate that the early increase is not wholly driven by calcitriol. Moreover, the extremes of severe vitamin D deficiency or genetic disorders of vitamin D physiology in the mother do not alter serum calcium, ionized calcium, phosphorus, PTH, or skeletal mineral content of the baby, as detailed in the companion review (492). These normal fetal parameters imply that maternal delivery of mineral is normal, or that the placenta is capable of extracting needed mineral regardless of a deficit in the maternal supply.…”

“…Also considered are the impacts that these adaptations have on normal biochemical and hormonal parameters of mineral homeostasis, the presentation and management of preexisting disorders of mineral and bone homeostasis, and long-term skeletal health of women. This paper is a companion to a recent review of fetal and neonatal mineral and skeletal homeostasis (492), which may be consulted for additional details and references that are pertinent to mineral and bone homeostasis of the offspring. This paper is also a substantial update and rethinking on the topic since the previous review in 1997 (499).…”

Scientific Opinion on Dietary Reference Values for phosphorus

“…Phosphorus is maintained in the fetal circulation at higher concentrations than in the mother, and such high levels appear necessary for the developing skeleton to accrete a normal amount of phosphorus by term. However, the factors and the molecular mechanism controlling placental phosphorus transport have not yet been explored (Mitchell and Jüppner, 2010;Kovacs, 2014). Phosphorus rises over the first 24-48 hours after delivery; after that, it declines towards adult values, consistent with resolution of transient hypoparathyroidism in the newborn (Kovacs, 2014).…”

Long-term pathological consequences of prenatal infection: beyond brain disorders

“…This seems surprising for various reasons. The prenatal period is not only a highly sensitive period for early brain development (99), but also for other biological systems that develop in utero, including the innate and adaptive immune systems (47,70), the cardiovascular system (46,60), the renal system (55,80), adipose tissue (140), and skeletal bones and muscles (20,68). It is, in fact, rather unlikely that maternal infection during pregnancy would specifically disrupt fetal brain development; instead, it may more generally represent a developmental stressor for the entire organism.…”