Elsevier

Early Human Development

Volume 91, Issue 11, November 2015, Pages 623-628
Early Human Development

Calcium, phosphorus, and bone metabolism in the fetus and newborn

https://doi.org/10.1016/j.earlhumdev.2015.08.007Get rights and content

Abstract

The placenta actively transports minerals whereas the intestines and kidneys may be nonessential for fetal mineral homeostasis. Mineral concentrations are higher in fetal blood than in adults in order for the developing skeleton to accrete adequate mineral content. Fetal bone development and serum mineral regulation are dependent upon parathyroid hormone (PTH) and PTH-related protein (PTHrP), but not calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, a switch from fetal to neonatal regulatory mechanisms is triggered by loss of the placental calcium infusion, onset of a breathing, and a postnatal fall in serum calcium and rise in phosphorus. This is followed by an increase in PTH, then a rise in calcitriol, and developmental changes in kidneys and intestines. Serum calcium increases and phosphorus declines over days. The intestines become the main source of mineral, while kidneys reabsorb mineral, and bone turnover contributes additional mineral to the circulation.

Introduction

Neonatal mineral and skeletal homeostasis represents a state of transition between fetal physiology, in which the placenta dominates to deliver and remove minerals, and adult physiology, in which the calciotropic hormones coordinate mineral handling by the intestines, kidneys, and bone. In order to understand this transition, it is first necessary to review the regulation of fetal mineral homeostasis, and then discuss the progressive changes that are provoked at birth.

The reader is referred to the author's much more comprehensive and detailed review that contains more than 750 citations of the primary data described herein [1]. Allotted space permits this brief monograph to serve only as a synopsis of the longer article.

Section snippets

Fetal calcium, phosphorus, and bone metabolism

The endochondral skeleton begins forming in the embryo, but it is not until the third trimester that substantial bone is formed and mineralized. The average human fetus has 30 g of calcium by term, with 80% of that accreted during the third trimester. Although the kidneys and intestines control the delivery and excretion of minerals in the adult, they are relatively unimportant for the normal fetus. Instead, it is the placenta that actively transports minerals from the maternal circulation, and

Neonatal calcium, phosphorus, and bone metabolism

When the umbilical cord is cut and the first breath is taken, these events trigger a rapid change in how mineral metabolism is regulated. The placental infusion and excretion of minerals are abruptly lost, while breathing causes an obligatory increase in blood pH. These alterations provoke a fall in serum calcium and ionized calcium. The intestines become the main source of minerals, the kidneys begin to reabsorb minerals, and bone turnover becomes more important to maintain serum mineral

Conclusions

Fetuses require PTHrP and PTH for placental mineral transfer, serum mineral concentrations, endochondral bone development, and skeletal mineralization, whereas calcitriol, calcitonin, and FGF23 are not essential (Fig. 1). It is during the neonatal period that intestinal calcium absorption becomes dependent upon vitamin D/calcitriol, and fetal kidneys become responsive to FGF23 (Fig. 1). This explains why rickets develops postnatally with disorders of vitamin D or FGF23.

Conflict of interest statement

None.

References (2)

  • C.S. Kovacs

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    Physiol Rev

    (2014)
  • C.S. Kovacs

    Fetal control of calcium and phosphate homeostasis — lessons from mouse models

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    Citation Excerpt :

    The peak intrauterine accretion rate ranges from 120 to 150 mg/kg/day for Ca and 50-85 mg/kg/day for P, and these are usually proposed as reference values for mineral intake in preterm infants.1,3,19,20 Approximately 80% of the required amounts of Ca and P are actively transported to the fetus via the placenta in the period from the third trimester to term birth; thus, preterm infants do not experience this complete period of mineral accumulation.18,21 Inadequate postnatal intake of Ca and P in growing preterm infants results in lower linear growth rates and MBDP,3,22 which may lead to poor chest wall compliance, difficulty weaning from the ventilator, and even bone fractures.20

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Grant support: Canadian Institutes of Health Research (grant #133413, #126469 and #84253) and Research & Development Corporation of Newfoundand and Labrador (grant #5404.1145.102).

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