Offspring Bone Mass Research Articles

Maternal vitamin D status and offspring bone fractures: prospective study over two decades in Aarhus City, Denmark.

BackgroundStudies investigating the association between maternal vitamin D status and offspring bone mass measured by dual-energy X-ray absorptiometry (DXA) during childhood have shown conflicting results.PurposeWe used occurrence of bone fractures up to the age of 18 as a measure reflecting offspring bone mass and related that to maternal vitamin D status.MethodsThe Danish Fetal Origins 1988 Cohort recruited 965 pregnant women during 1988–89 at their 30th gestation week antenatal midwife visit. A blood sample was drawn and serum was stored, which later was analyzed for the concentration of 25-hydroxyvitamin D (25(OH)D) by the liquid chromatography coupled with a tandem mass spectrometric method (LC-MS/MS). Outcome was diagnosis of first time bone fractures extracted from the Danish National Patient Register.ResultsVitamin D status was available for 850 women. The median (5th–95th percentile) 25(OH)D was 76.2 (23.0–152.1) nmol/l. During follow up 294 children were registered with at least one bone fracture diagnosis. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between maternal vitamin D status and first time bone fractures. However, there was a significantly increased hazard ratio (HR) during childhood for those who had maternal blood drawn in Dec/Jan/Feb compared with Jun/Jul/Aug (HR: 1.75, 95%CI: 1.11–2.74). Adjustment for vitamin D status strengthened this association (1.82, 1.12–2.97), which indicated a potential seasonal impact on offspring fractures independent of maternal vitamin D status. In a sensitivity analysis we found a borderline significant inverse association between continuous concentrations of 25(OH)D and offspring forearm fractures (P = 0.054).ConclusionOverall, our results did not substantiate an association between maternal vitamin D status and offspring bone fractures. Further studies on this subject are needed, but the study populations must be large enough to allow for subdivision of fractures.

O18. DXA Measures of Bone Mass in Mother, Father and Offspring: Results from the Southampton Women’s Survey

O18. DXA Measures of Bone Mass in Mother, Father and Offspring: Results from the Southampton Women’s Survey

Maternal Vitamin D Status During Pregnancy and Bone Mass in Offspring at 20 Years of Age: A Prospective Cohort Study

It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum samples collected at 18 weeks gestation were assayed for 25-hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L; 132 women (38.7%) were vitamin D-deficient (25OHD <50 nmol/L). After adjustment for season of sample collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6-32.7) g for BMC and 4.6 (95% CI, 0.1-9.1) mg/cm(2) for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm(2) , p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life.

Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era

Data from animal and human studies implicate maternal vitamin D deficiency during pregnancy as a significant risk factor for several adverse outcomes affecting maternal, fetal, and child health. The possible associations of maternal vitamin D status and offspring bone development comprise a significant public health issue. Evidence from randomized trials regarding maternal vitamin D supplementation for optimization of offspring bone mass is lacking. In the same field, data from observational studies suggest that vitamin D supplementation is not indicated. Conversely, supplementation studies provided evidence that vitamin D has beneficial effects on neonatal calcium homeostasis. Nevertheless, a series of issues, such as technical difficulties of current vitamin D assays and functional interplay among vitamin D analytes, prohibit arrival at safe conclusions. Future studies would benefit from adoption of a gold standard assay, which would unravel the functions of vitamin D analytes. This narrative review summarizes and discusses data from both observational and supplementation studies regarding maternal vitamin D status during pregnancy and offspring bone development.

Maternal perinatal diet induces developmental programming of bone architecture

Maternal high-fat (HF) diet can alter offspring metabolism via perinatal developmental programming. This study tests the hypothesis that maternal HF diet also induces perinatal programming of offspring bone mass and strength. We compared skeletal acquisition in pups from C57Bl/6J mice fed HF or normal diet from preconception through lactation. Three-week-old male and female pups from HF (HF-N) and normal mothers (N-N) were weaned onto normal diet. Outcomes at 14 and 26 weeks of age included body mass, body composition, whole-body bone mineral content (WBBMC) via peripheral dual-energy X-ray absorptiometry, femoral cortical and trabecular architecture via microcomputed tomography, and glucose tolerance. Female HF-N had normal body mass and glucose tolerance, with lower body fat (%) but higher serum leptin at 14 weeks vs. N-N (P<0.05 for both). WBBMC was 12% lower at 14 weeks and 5% lower at 26 weeks, but trabecular bone volume fraction was 20% higher at 14 weeks in female HF-N vs. N-N (P<0.05 for all). Male HF-N had normal body mass and mildly impaired glucose tolerance, with lower body fat (%) at 14 weeks and lower serum leptin at 26 weeks vs. N-N (P<0.05 for both). Serum insulin was higher at 14 weeks and lower at 26 weeks in HF-N vs. N-N (P<0.05). Trabecular BV/TV was 34% higher and cortical bone area was 6% higher at 14 weeks vs. N-N (P<0.05 for both). These data suggest that maternal HF diet has complex effects on offspring bone, supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis.

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

ObjectivesIn this study we investigate the relationships between placental size and neonatal bone mass and body composition, in a population-based cohort. Study design914 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. ResultsWe 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). ConclusionsWe 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.

Perinatal Maternal Dietary Supplementation of ω3-Fatty Acids Transiently Affects Bone Marrow Microenvironment, Osteoblast and Osteoclast Formation, and Bone Mass in Male Offspring

It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with ω3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-κB ligand, TNF-α, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health.

Evaluation of Methylation Status of the eNOS Promoter at Birth in Relation to Childhood Bone Mineral Content

Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year-old children. We used Sequenom MassARRAY to assess the methylation status of two CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9years (Lunar DPXL DXA instrument). Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex, there were strong positive associations between methylation status and the child's whole-body bone area (r=0.28, P=0.02), bone mineral content (r=0.34, P=0.005), and areal bone mineral density (r=0.34, P=0.005) at age 9years. These associations were independent of previously documented maternal determinants of offspring bone mass. Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.

Maternal and paternal relationships with offspring bone mass: response to Harvey et al.

Dear Editor, We thank Harvey et al. for their comment [1] regarding our paper comparing relationships of maternal and paternal smoking during pregnancy with offspring bone measures at age 10 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) [2]. We agree that the associations the authors report of maternal smoking and pre-pregnancy BMI with offspring whole body bone mineral content (BMC) at birth in the Southampton Women’s Survey, without similar paternal effects [1], provide some support for intrauterine influences on fetal bone development. However, we emphasise that in our study we aimed to assess whether any intrauterine effects on bone mineral accrual persist into childhood. The authors refer to differences between maternal and paternal associations in our complete case analysis as potentially representing an intrauterine effect. We point out that in our complete case, as in our multiple imputation analysis, there were similar-sized associations of maternal and paternal smoking with offspring total body BMC, bone area and bone mineral density in confounder-adjusted models; parental differences were apparent only in models for spinal bone outcomes. Furthermore, in both analyses, any associations of maternal smoking with offspring bone measures were positive, and thus in the opposite direction to those found with BMC at birth [1, 3, 4], and completely explained by the child’s height and, in particular, weight. Our findings, therefore, are not consistent with an adverse intrauterine effect of maternal smoking on bone development which persists into later childhood. In our other study referenced by the authors, the positive relationship of maternal BMI with offspring bone mass at age 10 years [5] is consistent with that reported at birth [1]. In our complete case, but not in our multiple imputation analysis, maternal effects were slightly stronger than paternal effects, so an intrauterine influence is plausible. However, detailed analyses suggested that these associations were completely driven by the association of maternal BMI with child’s BMI, rather than direct effects on bone development. Previous studies investigating maternal and paternal–offspring BMI associations have had inconsistent findings [6–9], although similar associations of maternal and paternal BMI with offspring BMI demonstrated in ALSPAC [6] and in the largest study to date [9] give support to our findings from multiple imputation of similarsized parental BMI associations with offspring bone mass. Finally, the authors suggest that maternal smoking status and BMI during/pre-pregnancy will be highly correlated with those post-pregnancy. We would expect that this is also true for fathers, suggesting that effects of parental exposures would be similar unless there was a specific effect of the maternal exposure during the intrauterine period [10]. Furthermore, we do not agree that an association of birth weight with later bone density is proof of an intrauterine effect. Smoking is the strongest environmental determinant of birth weight and strongly related to socioeconomic position (and largely explains the association of socioeconomic position with birth weight [11]); thus, familial socioeconomic position and associated lifestyles would C. Macdonald-Wallis (*) :G. Davey Smith :D. A. Lawlor MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK e-mail: C.Macdonald-Wallis@bristol.ac.uk

Bone turnover and maternal 25(OH) vitamin D3 levels during pregnancy and the postpartum period: should routine vitamin D supplementation be increased in pregnant women?

Objective To investigate the relationship between 25(OH) vitamin D3 levels and maternal bone turnover during pregnancy and lactation. Study design Thirty pregnant women and 30 healthy non-pregnant controls were included the study. The pregnant women were examined in the 12th, 25th and 32nd gestational weeks and 6 weeks after delivery. The controls were examined once. Serum concentrations of 25(OH) vitamin D3, parathyroid hormone (PTH), cross-linked C-terminal telopeptide of type I collagen (CTX), calcium, and phosphate were measured. Results In the 32nd week and the postpartum period, 25(OH) vitamin D3 deficiency rates were 13.3% and 33.3%, respectively. Serum 25(OH) vitamin D3 levels were below the detection limit in 10% and 33%, respectively, of the same subjects. In the control group, rates of 25(OH) vitamin D3 deficiency and “below detection limit” were 30% and 23%, respectively. While 25(OH) vitamin D3 and CTX levels were not correlated to each other in the first trimester, a negative correlation was found in the 2nd and 3rd trimesters and the postpartum period between 25(OH) vitamin D3 and CTX levels ( r = −0.472, p = 0.048; r = −0.893, p < 0.0001, r = −0.881, p < 0.001, respectively). No correlation between 25(OH) vitamin D3 and CTX levels was found in controls. Conclusion We consider that 25(OH) vitamin D3 supplementation of women could both decrease maternal bone resorption and lead to enhanced bone mass in offspring during later life. Since women are prone to 25(OH) vitamin D3 insufficiency, we suggest higher doses of 25(OH) vitamin D3 should be given to pregnant subjects.

Histone de-acetylases and epigenetic regulation

Histone de-acetylases and epigenetic regulation

Parental smoking during pregnancy and offspring bone mass at age 10 years: findings from a prospective birth cohort

SummaryWe investigated an intrauterine influence of maternal smoking during pregnancy on childhood bone mass. Daughters, but not sons, of mothers who smoked had higher bone mass at age 10 years. This appears to be due to familial factors related to parental smoking influencing increased offspring adiposity rather than a direct intrauterine effect.IntroductionNeonatal studies have demonstrated an adverse relationship between maternal smoking in pregnancy and foetal bone mineral accrual. We aimed to investigate an intrauterine influence of maternal smoking during pregnancy on offspring bone mass at mean age 9.9 years.MethodsWe compared associations of maternal and paternal smoking in pregnancy with offspring total body less head (TBLH) and spine bone mineral content (BMC), bone area (BA), bone mineral density (BMD) and area-adjusted BMC (ABMC) in 7,121 children in the Avon Longitudinal Study of Parents and Children.ResultsMaternal smoking in any trimester was associated with increased TBLH BMC, BA and BMD in girls (mean difference [95% CI] (sex-specific SD scores), 0.13 [0.05–0.22], 0.13 [0.04–0.21], 0.13 [0.04–0.22], respectively) but not boys (0.01 [−0.07–0.09], 0.00 [−0.08–0.08], 0.04 [−0.05–0.12]), and also with spine BMC, BA and BMD in girls (0.13 [0.03–0.23], 0.12 [0.03–0.22], 0.10 [0.00–0.21]) but not boys (0.03 [−0.06–0.12], 0.00 [−0.09–0.09], 0.05 [−0.04–0.14]), but not with ABMC. Paternal smoking associations were similar, with no statistical evidence for a difference between maternal and paternal effects. Maternal associations increased on adjustment for offspring birth weight and gestational age, but attenuated to the null after adjustment for current height and weight.ConclusionsWe found little evidence that maternal smoking was related to bone mass in boys. In girls, maternal smoking associations were similar to those of paternal smoking, suggesting that these were attributable to shared familial characteristics, not intrauterine mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-010-1415-y) contains supplementary material, which is available to authorized users.

Relation of maternal prepregnancy body mass index with offspring bone mass in childhood: is there evidence for an intrauterine effect?

Background: Evidence indicates that intrauterine skeletal development has implications for bone mass in later life and that maternal fat stores in pregnancy are important for fetal bone mineral accrual.Objective: We investigated whether childhood bone mass is influenced by maternal body mass index (BMI) via an intrauterine mechanism by comparing parental associations.Design: We conducted a multivariable regression analysis of 7121 children in the Avon Longitudinal Study of Parents and Children. Total body less head (TBLH) and spine bone measures were derived from dual-energy X-ray absorptiometry scans at a mean age of 9.9 y. Maternal and paternal BMI values were derived from self-reported weight and height during pregnancy.Results: Maternal prepregnancy BMI (SD score) was positively associated with offspring TBLH bone mineral content and bone mineral density (SD scores) [mean difference (95% CI): boys, 0.19 (0.16, 0.23) and 0.15 (0.12, 0.19), respectively; girls, 0.23 (0.19, 0.26) and 0.19 (0.16, 0.23), respectively] and spine bone mineral content and bone mineral density [boys, 0.20 (0.16, 0.24) and 0.18 (0.14, 0.22), respectively; girls, 0.22 (0.18, 0.26) and 0.21 (0.17, 0.25), respectively] and with TBLH and spine bone area–and spine area–adjusted bone mineral content. Associations of paternal BMI with these outcomes were similar, with no statistical evidence of a difference between maternal and paternal effects. Maternal associations were partly explained by offspring birth weight and gestational age and attenuated to the null after adjustment for offspring height and weight.Conclusion: The positive relation between maternal prepregnancy BMI and offspring bone mass is likely due to shared familial, genetic, and environmental characteristics rather than to an intrauterine mechanism.

P12 Maternal smoking during pregnancy and offspring bone mass at age 9 years

ObjectiveStudies in neonates have demonstrated an adverse relationship between maternal smoking during pregnancy and fetal bone mineral accrual. We aimed to investigate an intrauterine influence of maternal smoking in pregnancy...

Maternal Diet, Behaviour and Offspring Skeletal Health

Osteoporotic fracture has a major impact upon health, both in terms of acute and long term disability and economic cost. Peak bone mass, achieved in early adulthood, is a major determinant of osteoporosis risk in later life. Poor early growth predicts reduced bone mass, and so risk of fracture in later life. Maternal lifestyle, body build and 25(OH) vitamin D status predict offspring bone mass. Recent work has suggested epigenetic mechanisms as key to these observations. This review will explore the role of the early environment in determining later osteoporotic fracture risk.

Session 2: Other diseases Dietary management of osteoporosis throughout the life course

Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course. Thus, adequate Ca and vitamin D intake has been shown to reduce risk of fracture in old age. Other factors such as protein and vitamin K may also be important, although the evidence here is less strong. In childhood Ca or vitamin D supplementation trials have demonstrated modest short-term increases in bone mass, but the long-term implications have not been established. Over recent years it has become apparent that maternal nutrition may have critical and far-reaching persistent consequences for offspring health. Thus, reduced maternal fat stores and low levels of circulating 25-hydroxyvitamin D in pregnancy are associated with reduced bone mass in the offspring; placental Ca transport may be key to these relationships. Wider maternal dietary patterns have also been shown to predict offspring bone mass. These data suggest that an interventional approach aimed at specific micronutrients, such as vitamin D, should be complemented by general optimisation of the mother's diet and lifestyle in order to maximise intrauterine bone mineral accrual and postnatal skeletal growth and thus reduce the burden of osteoporotic fractures in future generations.

Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity

Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.

Impact of maternal veiling during pregnancy and socioeconomic status on offspring’s musculoskeletal health

The impact of maternal veiling during pregnancy and of socioeconomic status on offspring's bone mass was investigated in 326 healthy adolescents. Veiling during pregnancy was associated with decreased musculoskeletal parameters in the offspring boys, but not girls. SES was a significant predictor of bone mass in both genders. This study investigates the effects of maternal veiling during pregnancy, a surrogate for low vitamin D level, and socioeconomic status (SES), a surrogate of nutritional status, on their offspring's bone mass at adolescence. Three hundred and twenty-six healthy adolescents aged 13.1(2.0) years and their mothers were studied. The impact of maternal veiling on offspring's bone mass was evaluated through regression analyses. Outcome variables were bone mineral density (BMD) and content (BMC) at the spine, hip, and total body of the children. Predictors were maternal veiling during pregnancy and SES. Covariates were height, body composition, Tanner staging, calcium intake, vitamin D and exercise in children. In boys, adjusted analyses revealed that both maternal veiling during pregnancy and SES were significant predictors of bone mass, at multiple skeletal sites. In girls, SES but not maternal veiling during pregnancy was a significant predictor of bone mass at multiple sites. Maternal veiling during pregnancy was associated with decreased musculoskeletal parameters of boys, but not girls. SES was a significant predictor of bone mass in both genders. These findings may have profound implications on children's bone health.

Importance of genetic differences in developmental programming: gene by environment interactions in models of maternal dietary restriction

Importance of genetic differences in developmental programming: gene by environment interactions in models of maternal dietary restriction

Placental calcium transporter (PMCA3) gene expression predicts intrauterine bone mineral accrual

Evidence is accruing that environmental exposures during critical periods of early development induce persisting changes in skeletal growth, and alter fracture risk in later life. We have previously demonstrated that placental calcium transport, partly determined by maternal 25-(OH) vitamin D status, may underlie this phenomenon. However, the precise relationship between expression of calcium transport proteins in the human placenta, and neonatal bone mineral accrual in the offspring, remains unknown. Tissue samples from 70 human placentae were fast frozen in liquid nitrogen and stored at − 70 °C. A quantitative real time reverse transcriptase polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1–4, using beta-actin as a control gene. Neonatal whole body bone area, mineral content and areal density (BA, BMC, BMD) were measured within 2 weeks of birth using DXA. PMCA3 mRNA expression predicted BA ( r = 0.28, p = 0.02), BMC ( r = 0.25, p = 0.04), placental weight ( r = 0.26, p = 0.04) and birth weight ( r = 0.33, p = 0.006) of the neonate. In a multivariate model, the relationship between placental PMCA3 expression and neonatal BMC was independent of maternal height, pre-pregnant fat stores, parity, physical activity, smoking, and calcium intake ( p < 0.05). Expression of the placental calcium transporter PMCA3 mRNA predicts neonatal whole body bone mineral content. This association may explain, in part, the mechanism whereby a mother's 25(OH)-vitamin D stores influence her offspring's bone mass.