Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization

Abstract

Several factors have been found recently to have a significant impact on newborn bone mineral content (BMC) and developing fetal bone. Recently we showed that maternal vitamin D deficiency may affect fetal bone mineralization. Korean winter-born newborn infants had extremely low serum 25-hydroxyvitamin D (25-OHD), high serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker), and markedly lower (8 %) total body BMC than summer-born newborn infants. Infant total body BMC was positively correlated with cord serum 25-OHD and inversely correlated with ICTP, which was also negatively correlated with vitamin D status. In three separate studies on North American neonates we found markedly lower (8–12 %) BMC in summer newborn infants compared with winter newborn infants, the opposite of the findings for Korean neonates. The major reason for the conflicting BMC results might be the markedly different maternal vitamin D status of the North American and Korean subjects. Recently, we found evidence of decreased bone formation rates in infants who were small-for-gestational age (SGA) compared with infants who were appropriate-for-gestational age; we reported reduced BMC, cord serum osteocalcin (a marker of bone formation) and 1,25-dihydroxyvitamin D (the active metabolite of vitamin D), but no alterations in indices of fetal bone collagen metabolism. In theory, reduced utero-placental blood flow in SGA infants may result in reduced transplacental mineral supply and reduced fetal bone formation. Infants of diabetic mothers (IDM) have low BMC at birth, and infant BMC correlated inversely with poor control of diabetes in the mother, specifically first trimester maternal mean capillary blood glucose concentration, implying that factors early in pregnancy might have an effect on fetal BMC. The low BMC in IDM may be related to the decreased transplacental mineral transfer. Cord serum ICTP concentrations were higher in IDM than in control subjects, implying increased intrauterine bone resorption. BMC is consistently increased with increasing body weight and length in infants. Race and gender differences in BMC appear in early life, but not at birth. Ethanol consumption and smoking by the mother during pregnancy affect fetal skeletal development.