The effect of maternal vitamin D concentration on fetal bone

Abstract

Context: Vitamin D deficiency during pregnancy may be associated with suboptimal fetal growth, but direct evidence is lacking.

Objectives: The aim of the study was to validate a method for fetal femur volume (FV) measurement using three-dimensional ultrasound and to detect correlations between FV and maternal vitamin D concentration.

Design, setting, and participants: A novel method for assessing FV consists of three ultrasound measurements-femur length, proximal metaphyseal diameter (PMD), and midshaft diameter-and a volume equation; this was validated by comparing ultrasound to computed tomography measurements in six pregnancies after mid-trimester termination. This method was then applied in a cohort of healthy pregnant women participating in the Southampton Women Survey. Fetal three-dimensional ultrasound and maternal 25-hydroxyvitamin D [25(OH)D] levels were performed at 34 wk; dual-energy x-ray absorptiometry of the newborn was performed shortly after birth. Univariate and multiple linear regression analyses were performed between maternal characteristics and fetal outcomes.

Main outcome measures: We performed ultrasound measurements of the fetal femur.

Results: In 357 pregnant participants, serum 25(OH)D correlated significantly with FV (P = 0.006; r = 0.147) and PMD (P = 0.001; r = 0.176); FV also demonstrated positive univariate correlations with maternal height (P < 0.001; r = 0.246), weight (P = 0.003; r = 0.160), triceps skinfold thickness (P = 0.013; r = 0.134), and a borderline negative effect from smoking (P = 0.061). On multiple regression, independent predictors of FV were the maternal height and triceps skinfold thickness; the effect of 25(OH)D on FV was attenuated, but it remained significant for PMD.

Conclusion: 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.

Fig. 1.

Femur measurement technique using 3D ultrasound and the MITK software (near field at the bottom of the image). Before measurement, the orthogonal orientation axes are aligned with the longitudinal axis of the femur in planes A and C and their intersection positioned at the midshaft (left, A, B, C). The coronal A plane is then used for FL measurement (right A), and the sagittal C plane is used for PMD and MSD measurement (right C).

Fig. 2.

The effect of maternal vitamin D concentration, expressed as a binary variable, on FL (A), PMD (B), MSD (C), and FV (D); all ultrasound measurements are adjusted for GA; FV axis (D) is shown in logarithmic scale; box plots demonstrate mean values; error bars show the 95% confidence intervals; p = statistical significance from independent samples t-test.

Fig. 3.

Linear regression analyses of FL (A), PMD (B), MSD (C), and FV (D) against maternal vitamin D concentration; all ultrasound measurements are adjusted for GA; FV axis (D) is shown in logarithmic scale; p = statistical significance from univariate linear regression analysis; r = Pearson correlation coefficient.