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 Women's 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.

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.

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 infant's body composition in early childhood, we measured PHLDA2 mRNA levels in the term placenta of 102 infants whose mothers were participating in the Southampton Women's 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 child's 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.

Nonoperative management of adult splenic injury due to blunt trauma: a warning.

An analysis of 11 patients with splenic injury initially receiving nonoperative treatment revealed that 73 percent subsequently required surgery for delayed hemorrhage. The influence of age and the anatomic differences between the adult's spleen and child's spleen may account for the increased incidence of delayed bleeding seen in this series. Which patients might avoid surgical intervention cannot be predicted with certainty from the mechanism of injury or the lack of early physical signs and symptoms. The corresponding medical problems that often exist with the older patient may make nonoperative management, with the inherent risk of hypotension and large transfusion requirements, inappropriate. Although not advocating immediate splenectomy, we encourage early operative intervention with splenorrhaphy. Although improved diagnostic techniques will uncover a greater incidence of splenic injury, the inability to identify the nonoperative patient remains a clinical dilemma. The true role of nonoperative management of splenic injuries in the adult and the criteria for selection need to be further defined with larger prospective series. Although this approach may be useful for some patients, its application cannot be universal, and one must be willing to accept the consequences of delayed hemorrhage.