P Mahon

The Effect of Maternal Vitamin D Concentration on Fetal Bone

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.

Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey.

Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Womens Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.

Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass

Alterations in expression of the imprinted gene PHLDA2 are linked to low birth weight in both humans and the mouse. However birth weight is a summary measure of fetal growth and provides little information on the growth rate of the fetus in early and late pregnancy. To examine the relation of PHLDA2 expression with rates of fetal growth and explore associations with the infants body composition in early childhood, we measured PHLDA2 mRNA levels in the term placenta of 102 infants whose mothers were participating in the Southampton Womens Survey (SWS). Higher PHLDA2 expression was associated with a lower fetal femur growth velocity between 19 and 34 weeks gestation. In addition, higher placental PHLDA2 gene expression was associated with a lower childs bone mineral content at four years of age, measured using dual-energy X-ray absorptiometry. The results suggest that placental PHLDA2 may provide a biomarker for suboptimal skeletal growth in pregnancies uncomplicated by overt fetal growth restriction.

Placental size at 19 weeks predicts offspring bone mass at birth: findings from the Southampton Women's Survey.

OBJECTIVES In this study we investigate the relationships between placental size and neonatal bone mass and body composition, in a population-based cohort. STUDY DESIGN 914 mother-neonate pairs were included. Placental dimensions were measured via ultrasound at 19 weeks gestation. Dual X-ray absorptiometry (DXA) was performed on the neonates within the first two weeks of life. RESULTS We observed positive relationships between placental volume at 19 weeks, and neonatal bone area (BA; r = 0.26, p < 0.001), bone mineral content (BMC; r = 0.25, p < 0.001) and bone mineral density (BMD; r = 0.10, p = 0.001). Thus placental volume accounted for 6.25% and 1.2% of the variation in neonatal BMC and BMD respectively at birth. These associations remained after adjustment for maternal factors previously shown to be associated with neonatal bone mineral accrual (maternal height, smoking, walking speed in late pregnancy, serum 25(OH) vitamin D and triceps skinfold thickness). CONCLUSIONS We found that placental volume at 19 weeks gestation was positively associated with neonatal bone size and mineral content. These relationships appeared independent of those maternal factors known to be associated with neonatal bone mass, consistent with notion that such maternal influences might act through modulation of aspects of placental function, e.g. utero-placental blood flow or maternal nutrient concentrations, rather than placental size itself. Low placental volume early in pregnancy may be a marker of a reduced postnatal skeletal size and increased risk of later fracture.

Fetal and infant growth predict hip geometry at 6 y old: findings from the Southampton Women's Survey

Background:We investigated relationships between early growth and proximal femoral geometry at age 6 y in a prospective population-based cohort, the Southampton Women’s Survey.Methods:In 493 mother–offspring pairs, we assessed linear size using high-resolution ultrasound at 11, 19, and 34 wk gestation (femur length) and at birth and 1, 2, 3, 4, and 6 y (crown–heel length/height). SD scores were created and conditional regression modeling generated mutually independent growth variables. Children underwent hip dual-energy X-ray absorptiometry (DXA) at 6 y; hip structure analysis software yielded measures of geometry and strength.Results:There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 y, with the strongest relationships observed for femur growth from 19 to 34 wk gestation (β = 0.26 cm3/SD, P < 0.0001), and for height growth from birth to 1 y (β = 0.25 cm3/SD, P < 0.0001) and 1 to 2 y (β = 0.33 cm3/SD, P < 0.0001), with progressively weaker relationships over years 3 (β = 0.23 cm3/SD, P = 0.0002) and 4 (β = 0.10 cm3/SD, P = 0.18).Conclusion:These results demonstrate that growth before age 3 y predicts proximal femoral geometry at 6 y old. These data suggest critical periods in which there is capacity for long-term influence on the later skeletal growth trajectory.

Maternal vitamin D insufficiency and fetal bone development

S FROM THE BRS MEETING Abstracts Presented at the Bone Research Society Meeting Manchester, UK 23-25 June 2008s Presented at the Bone Research Society Meeting Manchester, UK 23-25 June 2008

OP33.09: The effect of maternal vitamin D concentration on fetal bone

Objectives: The aim of the present study was to explore the possible use of 3D Power Doppler Angiography (3D PDA) using VOCALTM software (GE Healthcare, USA) assessing different fetal cerebral regions in normal and growth restricted fetuses (IUGR). Methods: 77 AGA and 55 IUGR (24–36 ws gestation). IUGR were divided in 3 groups: group 1 (n = 28): Late onset IUGR (>34 ws) with normal bidimensional Doppler flow analysis, group 2 (n = 11): early onset IUGR (<34 ws) with abnormal umbilical artery (UA) pulsatilty index (PI), normal middle cerebral artery (MCA) PI and normal ductus venosus (DV) PI, group 3 (n = 16): early onset IUGR (<34 ws) with abnormal umbilical artery (UA) pulsatilty index (PI), abnormal MCA PI and pathological DV PI. Two regions of interest (ROI) were defined within the fetal brain. The first ROI (zone 1) is anterior respect the cavum septi pellucidi (CSP). The second ROI (zone 2) is obtained tracing a contour between the temporal bones as wide as the CSP. 3D-PDA vascular indexes (VI = vascularization, FI = flow, VFI = vascularization and flow) were determined in both areas for both AGA and IUGR fetuses by one operator. Results: VFI values demonstrated increased blood flow in frontal zone compared to control group (AGA) in ‘‘early onset IUGR’’ (in both groups 2–3 with and without abnormal 2D MCA findings). VI and VFI values demonstrated increased blood flow in frontal zone and decreased blood flow in temporal zone compared to control group (AGA) in ‘‘late onset IUGR’’ with preferential increment in bloody supply to the frontal region to protect general cognitive functions. Conclusions: 3DPDA analysis could be considered a valid method to identify earlier vascular redistribution in IUGR fetuses comparing to 2D velocimetry. 3DPDA could become an additional parameter to adjust the monitoring intervals in the evaluation of high risk fetuses.