Umbilical cord levels of sclerostin, placental weight, and birth weight are predictors of total bone mineral content in neonates

Abstract

Context: During pregnancy, changes occur in the maternal calcium homeostasis to fulfill fetal demand. We hypothesized that the fibroblast growth factor 23 (FGF23) system and Wnt signaling pathway are important for normal skeletal development in the offspring. Aims: Circulating a-klotho, FGF23, sclerostin, and 25-hydroxyvitamin D (25(OH)D) at the fetal and maternal sides of the placenta were measured to investigate associations with newborn bone mass independent of maternal BMI, calcium and phosphate levels, placental weight, and birth weight. Methods: In a prospective cohort of healthy pregnant women, the total body bone mineral content (BMC) in 202 newborns was measured by dual-energy X-ray absorptiometry. Maternal circulating levels of the biomarkers were measured at gestational weeks 30-32 and in umbilical cord plasma (UCP) at birth. Results: Mean a-klotho and sclerostin concentrations in the UCP were significantly higher than maternal levels (3004 vs 1077 pg/ml; P!0.001 and 629 vs 346 pg/ml; P!0.001 respectively), and mean 25(OH)D was lower (31 vs 45 nmol/l; P!0.001). The UCP and maternal FGF23 levels were similar. No significant effects of maternal biomarkers on BMC were found in regression analyses. Among UCP biomarkers, only UCP sclerostin was significantly associated with BMC in univariate analyses, and the effect remained significant after adjustment for birth weight and other confounders. Conclusions: We found that UCP sclerostin levels, birth weight, and placental weight were significant predictors of neonatal BMC but found no evidence for a main role of maternal levels of a-klotho, FGF23, sclerostin, or 25(OH)D nor of UCP levels of a-klotho, FGF23, or 25(OH)D.

Seasonal variation in maternal and umbilical cord 25(OH) vitamin D and their associations with neonatal adiposity

“…The relationship between maternal vitamin D and foetal bone development has recently been reviewed (31), but no association between maternal vitamin D levels and neonatal bone mineral content was demonstrated. This observation is in agreement with our recent findings, where we found that neither foetal nor maternal 25(OH)D seemed to have a major role in bone mass development in the neonates (32).…”

“…The study sample was based on a sub-cohort of 202 women from the STORK study: an observational, prospective study of determinants of foetal growth and birth weight in healthy pregnancies for which the details have been published previously (32,33). In short, the STORK cohort consists of women of Scandinavian heritage (nZ1031), who registered for obstetric care at Oslo University Hospital Rikshospitalet, from 2001 to 2008.…”

“…Thus, infants born to obese mothers had lower levels of 25(OH)D compared with infants born to lean mothers. Our cohort consists predominantly of normal-weight pregnant women (BMI 26.6, weeks [30][31][32], as only 7% were categorised as obese (BMIO 30 kg/m 2 ). The small amount of obese may explain the inconsistencies between the studies.…”

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

“…While the levels of FGF23 were similar in the maternal and the fetal compartment, those of a-klotho were higher in the umbilical cord plasma. However, neither FGF23 nor a-klotho was associated with fetal BMC (49).…”

“…A recent Scandinavian study (49) has found that the circulating levels of sclerostin were lower in the mother at the 30-32 weeks of pregnancy than in the umbilical cord at delivery. Interestingly, cord sclerostin, but not maternal sclerostin, was significantly associated with dual-energy X-ray absorptiometry (DXA)-measured total body bone mineral content (BMC) in the newborn.…”