Fetal and childhood growth patterns associated with bone mass in school-age children: the Generation R Study

Low birth weight is associated with lower bone accrual in children and peak bone mass in adults. We assessed how different patterns of longitudinal fetal and early childhood growth influence bone properties at school age. In 5431 children participating in a population-based prospective cohort study, we measured fetal growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth, 1, 2, 3, and 4 years of age. We analyzed these growth measurements in relation to total body (less head) BMD measured by DXA at age 6. We used conditional growth modeling; a technique which takes into account correlation between repeatedly measured growth measures. Our results showed that estimated fetal weight gain, femur length growth between 20 and 30 weeks of gestation, femur length growth between 30 weeks and birth, as well as all height and weight growth measurements from birth to 4 years of age were all positively associated with BMC, bone area (BA), and BMD (all p < 0.01). Fetal femur length growth between 30 weeks and birth was positively associated with BMC and BA (both p < 0.001), but not with BMD. Overall, childhood growth measurements exerted a larger influence on bone measures than fetal growth measures. The strongest effect estimate was observed during the first year of life. Children born small (<10th percentile) for gestational age (SGA) had lower BMC and BA, but not BMD, than children born appropriate for gestational age (AGA), whereas children born large (>90th percentile) for gestational age (LGA) had higher BMC and BA (all p < 0.001). These differences were no longer present in children showing subsequent accelerated and decelerated infant growth, respectively. We conclude that both fetal and childhood growth patterns are associated with bone mineral accrual, showing the strongest effect estimates in infancy. Compensatory infant growth counteracts the adverse consequences of fetal growth restriction on bone development.