The Gestational Effects of Maternal Bone Marker Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review

Fetal exposure in adverse environmental factors during intrauterine life can lead to various biological adjustments, affecting not only in utero development of the conceptus, but also its later metabolic and endocrine wellbeing. During human gestation, maternal bone turnover increases, as reflected by molecules involved in bone metabolism, such as vitamin D, osteocalcin, sclerostin, sRANKL, and osteoprotegerin; however, recent studies support their emerging role in endocrine functions and glucose homeostasis regulation. Herein, we sought to systematically review current knowledge on the effects of aforementioned maternal bone biomarkers during pregnancy on fetal intrauterine growth and metabolism, neonatal anthropometric measures at birth, as well as on future endocrine and metabolic wellbeing of the offspring. A growing body of literature converges on the view that maternal bone turnover is likely implicated in fetal growth, and at least to some extent, in neonatal and childhood body composition and metabolic wellbeing. Maternal sclerostin and sRANKL are positively linked with fetal abdominal circumference and subcutaneous fat deposition, contributing to greater birthweights. Vitamin D deficiency correlates with lower birthweights, while research is still needed on intrauterine fetal metabolism, as well as on vitamin D dosing supplementation during pregnancy, to diminish the risks of low birthweight or SGA neonates in high-risk populations.