Recent findings suggest that maternal vitamin D insufficiency during pregnancy has consequences for the offspring's bone health in later life. To investigate whether maternal vitamin D insufficiency affects fetal femur growth in ways similar to those seen in childhood rickets and study the timing during gestation of any effect of maternal vitamin D status, we studied 424 pregnant women within a prospective longitudinal study of maternal nutrition and lifestyle before and during pregnancy (Southampton Women's Survey). Using highresolution 3D ultrasound, we measured fetal femur length and distal metaphyseal cross-sectional area, together with the ratio of femoral metaphyseal cross-sectional area to femur length (femoral splaying index). Lower maternal 25-hydroxyvitamin vitamin D concentration was not related to fetal femur length but was associated with greater femoral metaphyseal cross-sectional area and a higher femoral splaying index at 19 weeks' gestation [r ¼ À0.16, 95% confidence interbal (CI) À0.25 to À0.06 and r ¼ À0.17, 95% CI À0.26 to À0.07, respectively] and at 34 weeks' gestation (r ¼ -0.10, 95% CI À0.20 to 0.00 and r ¼ À0.11, 95% CI À0.21 to À0.01, respectively). Three groups of women were identified with 25-hydroxyvitamin vitamin D concentrations that were sufficient/borderline (>50 nmol/L, 63.4%), insufficient (25 to 50 nmol/L, 30.7%), and deficient ( 25 nmol/L, 5.9%). Across these groups, the geometric mean femoral splaying indices at 19 weeks' gestation increased from 0.074 (sufficient/borderline) to 0.078 (insufficient) and 0.084 (deficient). Our observations suggest that maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks' gestation. This suggests that measures to improve maternal vitamin D status should be instituted in early pregnancy. ß
Using a novel method for assessing FV, independent predictors of femoral size were maternal height, adiposity, and serum vitamin D. Future trials should establish whether pregnancy supplementation with vitamin D is beneficial for the fetal skeleton, using FV and PMD as fetal outcome measures.
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