Bone development in fetuses with intrauterine growth restriction caused by maternal endocrine-metabolic dysfunctions

Intrauterine growth restriction (IUGR) affects a large proportion of infants, particularly in underdeveloped countries. Among the main causes of IUGR, maternal endocrine-metabolic dysfunction is highlighted, either due to its high incidence or due to the severity of the immediate and mediated changes that these dysfunctions cause in the fetus and the mother. Although the effects of endocrine and metabolic disorders have been widely researched, there are still no reviews that bring together and summarize the effects of these conditions on bone development in cases of IUGR. Therefore, the present literature review was conducted with the aim of discussing bone changes observed in fetuses with IUGR caused by maternal endocrine-metabolic dysfunction. The main endocrine dysfunctions that occur with IUGR include maternal hyperthyroidism, hypothyroidism, and hypoparathyroidism. Diabetes mellitus, hypertensive disorders, and obesity are the most important maternal metabolic dysfunctions that compromise fetal growth. The bone changes reported in the fetus are, for the most part, due to damage to cell proliferation and differentiation, as well as failures in the synthesis and mineralization of the extracellular matrix, which results in shortening and fragility of the bones. Some maternal dysfunctions, such as hyperthyroidism, have been widely studied, whereas conditions such as hypoparathyroidism and gestational hypertensive disorders require further study regarding the mechanisms underlying the development of bone changes. Similarly, there is a gap in the literature regarding changes related to intramembranous ossification, as most published articles only describe changes in endochondral bone formation associated with IUGR. Furthermore, there is a need for more research aimed at elucidating the late postnatal changes that occur in the skeletons of individuals affected by IUGR and their possible relationships with adult diseases, such as osteoarthritis and osteoporosis.