Placental volume at 11 weeks is associated with offspring bone mass at birth and in later childhood: Findings from the Southampton Women's Survey.

OBJECTIVES: To investigate associations between placental volume (PV) at 11 weeks' gestation and offspring bone outcomes at birth, 6 years and 8 years. METHODS: 3D ultrasound scanning was used to assess 11 week PV in a subset (n = 236) of the Southampton Women's Survey (a prospective mother-offspring cohort). Maternal anthropometric measures and lifestyle information were obtained pre-pregnancy and at 11 weeks' gestation. Offspring dual-energy x-ray absorptiometry scanning was performed within 2 weeks postnatally and at 6 and 8 years. Linear regression was used to assess associations between PV and bone outcomes, adjusting for offspring age at DXA and sex, and maternal age, height, smoking status, walking speed and triceps skinfold thickness. ß are SD change in bone outcome per SD change in PV. RESULTS: In adjusted models, 11 week PV was positively associated with bone area (BA) at all time points, with evidence of persisting associations with increasing childhood age (birth: n = 80, ß = 0.23 [95%CI = 0.03, 0.42], 6 years: n = 110, ß = 0.17 [-0.01, 0.36], 8 years: n = 85, ß = 0.13 [-0.09, 0.36]). Similar associations between 11 week PV and bone mineral content (BMC) were observed. Associations with size-corrected bone mineral content were weaker at birth but strengthened in later childhood (birth: n = 78, ß = 0.07 [-0.21, 0.35], 6 years: n = 107, ß = 0.13 [-0.08, 0.34], 8 years: n = 71, ß = 0.19 [-0.05, 0.43]). CONCLUSIONS: 11 week PV is associated with DXA bone measures at birth, with evidence of persisting associations into later childhood. Further work is required to elucidate the contributions of placental morphology and function to gestational influences on skeletal development.

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Breech presentation is associated with lower bone mass and area: findings from the Southampton Women's Survey.

We compared bone outcomes in children with breech and cephalic presentation at delivery. Neonatal whole-body bone mineral content (BMC) and area were lower in children with breech presentation. At 4 years, no differences in whole-body or spine measures were found, but hip BMC and area were lower after breech presentation. INTRODUCTION: Breech presentation is associated with altered joint shape and hip dysplasias, but effects on bone mineral content (BMC), area (BA) and density (BMD) are unknown. METHODS: In the prospective Southampton Women's Survey mother-offspring cohort, whole-body bone outcomes were measured using dual-energy X-ray absorptiometry (DXA) in 1430 offspring, as neonates (mean age 6 days, n = 965, 39 with a breech presentation at birth) and/or at age 4.1 years (n = 999, 39 breech). Hip and spine bone outcomes were also measured at age 4 years. RESULTS: Neonates with breech presentation had 4.2 g lower whole-body BMC (95% CI -7.4 to - 0.9 g, P = 0.012) and 5.9 cm2 lower BA (- 10.8 to - 1.0 cm2, P = 0.019), but BMD was similar between groups (mean difference - 0.007, - 0.016 to 0.002 g/cm2, P = 0.146) adjusting for sex, maternal smoking, gestational diabetes, mode of delivery, social class, parity, ethnicity, age at scan, birthweight, gestational age and crown-heel length. There were no associations between breech presentation and whole-body outcomes at age 4 years, but, in similarly adjusted models, regional DXA (not available in infants) showed that breech presentation was associated with lower hip BMC (- 0.51, - 0.98 to - 0.04 g, P = 0.034) and BA (- 0.67, - 1.28 to - 0.07 cm2, P = 0.03) but not with BMD (- 0.009, - 0.029 to 0.012 g, P = 0.408), or spine outcomes. CONCLUSIONS: These results suggest that breech presentation is associated with lower neonatal whole-body BMC and BA, which may relate to altered prenatal loading in babies occupying a breech position; these differences did not persist into later childhood. Modest differences in 4-year hip BMC and BA require further investigation.

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.

Maternal predictors of neonatal bone size and geometry: the Southampton Women's Survey.

Early growth is associated with later risk of osteoporosis and fractures. In this study, we aimed to evaluate the relationships between maternal lifestyle and body composition and neonatal bone size, geometry and density in the offspring. Participants were recruited from the Southampton Women's Survey, a unique prospective cohort of 12,500 initially non-pregnant women aged 20-34 years, resident in Southampton, UK. These women were studied in detail before and during pregnancy, and the offspring underwent anthropometric and bone mineral assessment (using dual energy-X-ray absorptiometry) at birth. A total of 841 mother-baby pairs were studied (443 boys and 398 girls). The independent predictors of greater neonatal whole body bone area (BA) and bone mineral content included greater maternal birthweight, height, parity, triceps skinfold thickness and lower walking speed in late pregnancy. Maternal smoking was independently associated with lower neonatal bone mass. Neonatal BA adjusted for birth length (a measure of bone width) was predicted positively by maternal parity and late pregnancy triceps skinfold thickness and negatively by late pregnancy walking speed. These findings were similar in both genders. We have confirmed, in a large cohort, previous findings that maternal lifestyle and body build predict neonatal bone mineral; additionally, maternal parity and fat stores and walking speed in late pregnancy were associated with neonatal bone geometry. These findings may suggest novel public health strategies to reduce the burden of osteoporotic fracture in future generations.

Women of lower educational attainment have lower food involvement and eat less fruit and vegetables.

Women who leave school with few or no educational qualifications are less likely to have diets that meet current recommendations than women who attain more qualifications at school. We hypothesise that lower 'food involvement', meaning that food has a lower level of importance in their lives, explains the poorer quality diets of women of lower educational attainment. We administered Bell and Marshall [(2003). The construct of food involvement in behavioral research: Scale development and validation. Appetite, 40, 235-244.] Food Involvement scale to 242 women of varied educational attainment, of whom 127 were also asked how often they ate fruit and vegetables. Women's food involvement decreased with decreasing educational attainment. Forty-two percent of women who had no educational qualifications were in the lowest quarter of the food involvement score, compared with 12% of women with degrees. Women with lower scores on the food involvement scale also reported eating fruit and vegetables less often. The odds of eating fewer fruit and vegetables rose with lower educational attainment and with lower food involvement scores, suggesting that each has an independent effect. We have shown that the Food Involvement scale discriminates between women, is associated with other characteristics and predicts dietary quality. We now plan to use it in a larger, representative population of women of lower educational attainment to examine its role along with other psychological variables in determining dietary quality.

Stability of dietary patterns in young women over a 2-year period.

OBJECTIVE: To examine the stability of dietary patterns in young women over a two-year period and to identify factors that influence stability. DESIGN: A food frequency questionnaire was used to assess diet. In a subgroup, this was repeated after 2 years. Questions were asked about major changes to diet over this time. Dietary patterns were identified using principal components analysis and pattern scores were compared at the two time points. The consumption of foods was also examined. The relationship between change in pattern scores and socio-demographic factors and body mass index was assessed. SETTING: The Southampton Women's Survey, a prospective study of diet, health and lifestyle in young women and their influences on fetal growth. SUBJECTS: A subgroup of 94 women from a cohort of 6129 nonpregnant women aged 20-34 years. RESULTS: Two dietary patterns, labelled 'prudent' and 'high energy', were identified. Spearman correlation coefficients between the initial and repeat scores for the prudent and high-energy patterns were 0.81 and 0.64, respectively. Average changes (repeat - initial) were 0.13 and -0.01 SD of initial score. Change in prudent dietary pattern score was influenced by amount of strenuous exercise taken and by changes in partnership status. An increase in high-energy pattern score was associated with lower social class. CONCLUSIONS: Dietary patterns in young women are reasonably stable over a 2-year period. This suggests that dietary patterns identified in the recent past may provide useful information about current dietary patterns.

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 degrees 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.

Umbilical cord leptin predicts neonatal bone mass.

Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences on bone development during intrauterine and early postnatal life. A potential role for fetal leptin in mediating these effects is suggested by animal studies showing that leptin influences prenatal osteoblast growth and development, and that fetal leptin concentrations are altered by changes in maternal nutrition. In a group of term human infants we reported previously that maternal birthweight, smoking, fat mass, and exercise during late pregnancy independently predict neonatal bone mass. To investigate the potential role of leptin in mediating these effects, we now relate leptin concentrations in umbilical venous serum to neonatal bone mass and body composition in 117 infants. There were strong positive associations between umbilical venous leptin concentration and each of whole body bone mineral contents (BMC) (r = 0.42, P < or = 0.001) and estimated volumetric bone density (r = 0.21, P = 0.02); whole body lean mass (r = 0.21, P < or = 0.024); and whole body fat mass (r = 0.60, P < 0.001). The associations with neonatal BMC and fat mass, but not with lean mass, were independent of associations that we have reported previously between cord serum insulin-like growth factor 1 (IGF-1) concentrations and neonatal body composition. Among the maternal determinants of neonatal bone mass, cord leptin explained the relationship with maternal fat stores, but not those with the mother's own birthweight, smoking, or physical activity. We conclude that umbilical venous leptin predicts both the size of the neonatal skeleton and its estimated volumetric mineral density. In addition, among previously documented maternal determinants of neonatal bone mass in healthy pregnancies, maternal fat stores may mediate their effect on fetal bone accrual through variation in fetal leptin concentrations.

Impact of educational attainment on the quality of young women's diets.

OBJECTIVE: New findings, that relate poor foetal growth to long-term outcomes, highlight the need to understand more about the nature of women's diets before and during pregnancy. This study examines the influence of sociodemographic and anthropometric factors on the quality of the diets of young women in the UK. DESIGN: Diet was assessed by an interviewer-administered food frequency questionnaire. A single diet score was calculated for each woman using the first component defined by principal components analysis. SETTING: Southampton, UK. SUBJECTS: A total of 6125 non pregnant women aged 20-34 y. RESULTS: The diets of women with low diet scores were characterised by low intakes of fruit and vegetables, wholemeal bread, rice and pasta, yogurt, and breakfast cereals, but high intakes of chips and roast potatoes, sugar, white bread, red, and processed meat and full-fat dairy products. Educational attainment was the most important factor related to the diet score. In all, 55% (95% CI 50-59%) of women with no educational qualifications had scores in the lowest quarter of the distribution, compared with only 3% (95% CI 2-4%) of those who had a degree. Smoking, watching television, lack of strenuous exercise, and living with children were also associated with lower diet scores. After taking these factors into account, no other factor including social class, the deprivation score of the neighbourhood, or receipt of benefits added more than 1% to the variance in the diet score. CONCLUSIONS: Poor achievement at school defines a substantial group of women in the UK who may be vulnerable. Many of these women have poor diets that are not simply a result of the level of deprivation in their neighbourhood, or of living at a level of poverty that entitles them to benefits. We suggest that it is a priority to identify and to address the barriers that prevent these women from improving the quality of their diets. SPONSORSHIP: The study was funded by the Dunhill Medical Trust, the University of Southampton and the Medical Research Council.