0603. Does intrauterine programming affect bone status in childhood?

One of the themes of this series of clinical excerpts has revolved around the foetal determinants of adult pathology and the emerging role of the neonatologist and paediatrican in preventing late onset disease. Much has been written about intrauterine growth retardation and subsequent metabolic and cardiovascular complications, and it seems we may also have to be concerned about the relationship between maternal vitamin D status and subsequent bone mass. Previous research has shown that poor intrauterine and childhood growth are associated with a doubling of the risk of hip fracture 60 years on, but the relationship between this risk and maternal D status during pregnancy has not been directly assessed. This issue was the subject of a recently-published longitudinal study that commenced almost 15 years ago and in which maternal and neonatal parameters were matched to childhood measures at ±9 years. Bone mass was measured in 198 children from an original sample of 596 Southampton women and their infants. It was found that almost half of the 198 mothers had late pregnancy D levels that were insufficient (31%) or frankly deficient (18%) and that bone mass in their children was lower at 9 years than in those whose mothers were D-replete. These findings were independent of growth, exercise or nutritional factors in the children, and suggest that there has been intrauterine epigenetic programming (e.g. involving methylation status of imprinted genes that regulate foetal and placental growth as well as specific transport systems). This may result in an impairment of placental calcium transport (given that there was also a relationship between cord calcium levels and subsequent bone mass). The implication here is that maternal correction of D-deficiency or insufficiency during pregnancy will prevent the consequences whereas postnatal supplementation or sun-exposure of the infant and child might not.

Read more:
Lancet 2006; 367: 36-43
Best Pract Res Clin Endocrinol Metab 2002; 16: 349-67
Osteoporosis Int 2001; 12: 623-9
Science 2004; 305: 1733-6