Insights into the programming of bone development from the Avon Longitudinal Study of Parents and Children (ALSPAC)

We examined associations between proxy measures of in utero nutrition and total body bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) assessed at age 9.9 y in the Avon Longitudinal Study of Parents and Children (ALSPAC). There were positive relations between birth weight and BMC, BA, and BMD. These associations were explained by the co-association of birth weight with body size in later childhood. In height- and weight-adjusted analyses, an inverse association was observed between birth weight and BMD at age 9.9 y, which suggests that birth weight had a negative influence on bone mass after relations with bone and body size were taken into account. In analyses of associations between bone mass at age 9 y and background ultraviolet B exposure during the third trimester of pregnancy (a proxy measure for maternal vitamin D status), maternal ultraviolet B exposure was positively related to BMC, BA, and BMD. After adjustment for height, these associations were only partially attenuated, which suggests that maternal ultraviolet B exposure affected skeletal size and mass independently of longitudinal growth, possibly by the increase of periosteal expansion. There was a positive relation between maternal folate intake and BMD of the spine subregion independent of body size. Although a co-association with folate intake in childhood could explain this relation, the maternal methylenetetrahydrofolate reductase (MTHFR) genotype affected spine BMD independently of the child MTHFR genotype, which suggests that maternal folate status has an independent effect on bone development of offspring. Together, these results confirm that there is a relation between bone development in childhood and several proxy measures for nutritional status in utero.