Intrauterine growth restriction may not suppress bone formation at term, as indicated by circulating concentrations of undercarboxylated osteocalcin and Dickkopf-1

Abstract

The objective was to investigate circulating concentrations of bone formation markers (undercarboxylated osteocalcin [Glu-OC], an established marker of bone formation during fetal and early postnatal life], and Dickkopf-1 [DKK-1], a natural inhibitor of osteoblastogenesis during fetal development]) in intrauterine-growth–restricted (IUGR; associated with impaired fetal skeletal development) and appropriate-for-gestational-age (AGA) pregnancies. Circulating concentrations of Glu-OC and DKK-1 were determined by enzyme immunoassay in 40 mothers and their 20 asymmetric IUGR and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and 4 (N4). Parametric tests were applied in the statistical analysis. No significant differences in Glu-OC concentrations were observed between IUGR and AGA groups, whereas fetal DKK-1 concentrations were lower in the IUGR group (P = .028). In both groups, maternal Glu-OC and DKK-1 concentrations were lower than fetal, N1, and N4 concentrations (P ≤ .012 in all cases), whereas fetal Glu-OC concentrations were higher than N1 and N4 ones (P ≤ .037 in all cases). In addition, N1 Glu-OC concentrations were higher than N4 concentrations (P = .047). Finally, maternal Glu-OC and DKK-1 concentrations positively correlated with fetal, N1, and N4 ones (r ≥ 0.404, P ≤ .01 in all cases). Fetal/neonatal bone formation may not be impaired in full-term asymmetric IUGR infants, as indicated by the similar Glu-OC concentrations in both groups. Fetal DDK-1 concentrations are lower in the IUGR group, representing probably a compensatory mechanism, favoring the formation of mineralized bone. Fetal/neonatal bone turnover is markedly enhanced compared with maternal one and seems to be associated with the latter in both late pregnancy and early postpartum.