Differential relationships between parent-child DXA and pQCT bone measures: Results from the Southampton Women's Survey.

AIM: To investigate the associations between indices of bone health in childhood and corresponding parental measures. METHODS: The Southampton Women's Survey characterised 12,583 non-pregnant women aged 20-34 years; 3158 subsequently had singleton live births. In a subset, dual-energy X-ray absorptiometry (DXA) measurements of bone area (BA), bone mineral content (BMC) and areal bone mineral density (aBMD) lumbar spine and total hip were obtained in the parent/offspring (aged 8-9 years) trios. Another subset of children (aged 6-7 years), and their parents, had peripheral quantitative computed tomography (pQCT; 4% and 38% tibia) measures. Using multivariable linear regression we examined relationships between mother/father and offspring, adjusting for parental age, habitual walking speed and education; offspring age and sex; and the corresponding bone measure in the other parent (ß-coefficients (95%CI) unit/unit for each bone measure). RESULTS: Data were available for 260 trios with DXA and 99 with pQCT. There were positive associations for BA, BMC and aBMD between either parent and offspring. Mother-child associations were of greater magnitude than father-child; for example, mother-child aBMD (ß = 0.26 g·cm-2/g·cm-2 (0.21,0.32)) and father-child aBMD (ß = 0.16 g·cm-2/g·cm-2 (0.11,0.21)), P-difference in ß = 0.007. In the subset with pQCT there was a positive association for mother-offspring 4% tibial total area (ß = 0.33 mm2/mm2 (0.17,0.48)), but little evidence of a father-offspring association (ß = -0.06 mm2/mm2 (-0.17,0.06)). In contrast offspring 38% cortical density was more strongly associated with this measure in fathers (ß = 0.48 mg·cm-3/mg·cm-3 (0.15,0.82)) than mothers (ß = 0.27 mg·cm-3/mg·cm-3 (-0.03,0.56)). In general mother-father differences were attenuated by adjustment for height. CONCLUSIONS: Whilst offspring bone measures are independently associated with those of either parent, the magnitude of the association is often greater for maternal than paternal relationships. These findings are consistent with an in utero influence on offspring growth but might also reflect genetic and/or epigenetic parent of origin effects. SUMMARY: In an established parent-offspring cohort, associations between parent and offspring bone indices were generally greater in magnitude for mother-offspring than father-offspring relationships.

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.

Development of a Short Questionnaire to Assess Diet Quality among Older Community-Dwelling Adults.

OBJECTIVE: To evaluate the use of a short questionnaire to assess diet quality in older adults. DESIGN: Cross-sectional study. SETTING: Hertfordshire, UK. PARTICIPANTS: 3217 community-dwelling older adults (59-73 years). MEASUREMENTS: Diet was assessed using an administered food frequency questionnaire (FFQ); two measures of diet quality were defined by calculating participants' 'prudent diet' scores, firstly from a principal component analysis of the data from the full FFQ (129 items) and, secondly, from a short version of the FFQ (including 24 indicator foods). Scores calculated from the full and short FFQ were compared with nutrient intake and blood concentrations of vitamin C and lipids. RESULTS: Prudent diet scores calculated from the full FFQ and short FFQ were highly correlated (0.912 in men, 0.904 in women). The pattern of associations between nutrient intake (full FFQ) and diet scores calculated using the short and full FFQs were very similar, both for men and women. Prudent diet scores calculated from the full and short FFQs also showed comparable patterns of association with blood measurements: in men and women, both scores were positively associated with plasma vitamin C concentration and serum HDL; in women, an inverse association with serum triglycerides was also observed. CONCLUSIONS: A short food-based questionnaire provides useful information about the diet quality of older adults. This simple tool does not require nutrient analysis, and has the potential to be of value to non-specialist researchers.

Modifiable risk factors of maternal postpartum weight retention: an analysis of their combined impact and potential opportunities for prevention.

BACKGROUND/OBJECTIVES: Pregnancy triggers a physiological change in weight status. Postpartum weight retention in the childbearing years can substantially alter a woman's weight gain trajectory, with several potential contributing factors identified. Most research has relied on women's recall of pre-pregnancy weight during pregnancy or later, and not considered risk factors in combination. Using measured pre-pregnancy weight, this study aimed to examine the associations of maternal postpartum weight retention with parity, pre-pregnancy BMI, excessive gestational weight gain (GWG), maternal serum vitamin D concentration and dietary Glycaemic Index in early and late pregnancy, and breastfeeding duration, including analysis of the combined impact of potentially modifiable risk factors. SUBJECTS/METHODS: Prospective cohort study of 12 583 non-pregnant women aged 20-34 years in Southampton (UK) who were assessed prior to pregnancy, with those who subsequently became pregnant followed up in early and late gestation, and after delivery (n=2559 in the final sample). Linear regression models examined potential predictors of weight retention in adjusted individual and multivariate analyses, and as a risk factor score. RESULTS: Compared with pre-pregnancy weight, 73% of women retained some weight at 6 months postpartum (mean (s.d.): 3.5 (6.2) kg). In the adjusted multivariate model, women who were primiparous, had a lower pre-pregnancy BMI, excessive GWG, a lower early pregnancy vitamin D concentration and breastfed for <6 months had greater weight retention 6 months postpartum (P<0.05 for all variables). For each additional modifiable risk factor (excessive GWG, low vitamin D concentration in early pregnancy and short breastfeeding duration; scale 0-3), women retained an additional 2.49 kg (95% CI: 2.16, 2.82; P<0.001). CONCLUSIONS: Having a greater number of modifiable risk factors was associated with greater weight retention 6 months postpartum. Initiatives supporting women to target these risk factors in the years prior to, during and after pregnancy could impact on their weight gain trajectory and later risk of adverse weight-related outcomes.

Maternal stress and psychological distress preconception: association with offspring atopic eczema at age 12 months.

BACKGROUND: Perinatal maternal stress and low mood have been linked to offspring atopic eczema. OBJECTIVES: To examine the relation of maternal stress/mood with atopic eczema in the offspring, focusing particularly on stress/psychological distress preconception. METHODS: At recruitment in the UK Southampton Women's Survey, preconception maternal reports of perceived stress in daily living and the effect of stress on health were recorded; in a subsample, psychological distress was assessed (12-item General Health Questionnaire). Infants were followed up at ages 6 (n = 2956) and 12 (n = 2872) months and atopic eczema ascertained (based on UK Working Party Criteria for the Definition of Atopic Dermatitis). At 6 months post-partum, mothers were asked if they had experienced symptoms of low mood since childbirth and completed the Edinburgh Postnatal Depression Scale. RESULTS: Preconception perceived stress affecting health [OR 1.21 (95% CI 1.08-1.35), P = 0.001] and stress in daily living [OR 1.16 (1.03-1.30), P = 0.014] were associated with an increased risk of offspring atopic eczema at age 12 months but not at 6 months, robust to adjustment for potentially confounding variables. Findings were similar for maternal psychological distress preconception. Low maternal mood between delivery and 6 months post-partum was associated with an increased risk of infantile atopic eczema at age 12 months, but no significant association between post-natal mood and atopic eczema was seen after taking account of preconception stress. CONCLUSION AND CLINICAL RELEVANCE: Our data provide novel evidence linking maternal stress at preconception to atopic eczema risk, supporting a developmental contribution to the aetiology of atopic eczema and pointing to potentially modifiable influences.

Higher maternal serum concentrations of nicotinamide and related metabolites in late pregnancy are associated with a lower risk of offspring atopic eczema at age 12 months.

BACKGROUND: Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema. OBJECTIVE: To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring. METHODS: Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry (n = 497) and related to the odds ratio of infantile atopic eczema. RESULTS: Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables. CONCLUSION AND CLINICAL RELEVANCE: This is the first study linking maternal serum concentrations of nicotinamide and related metabolites to the risk of atopic eczema in the offspring. The findings point to potentially modifiable maternal influences on this complex and highly prevalent condition.

Age at introduction of solid foods and feeding difficulties in childhood: findings from the Southampton Women's Survey.

This study aimed to determine whether age at introduction of solid foods was associated with feeding difficulties at 3 years of age. The present study was carried out using data from the Southampton Women's Survey (SWS). Women enrolled in the SWS who subsequently became pregnant were followed-up during pregnancy and postpartum, and the offspring have been studied through childhood. Maternal socio-demographic and anthropometric data and child anthropometric and feeding data were collected through interviews and self-administered questionnaires. When the children were 3 years of age, mothers/carers rated six potential child feeding difficulty questions on a four-point Likert scale, including one general question and five specific feeding difficulty questions. Age at introduction of solids as a predictor of feeding difficulties was examined in 2389 mother-child pairs, adjusting for child (age last breast fed, sex, gestation) and maternal characteristics (parity, pre-pregnancy BMI, age, education, employment, parenting difficulties, diet quality). The majority of mothers/carers (61 %) reported some feeding difficulties (general feeding difficulty question) at 3 years of age, specifically with their child eating enough food (61 %), eating the right food (66 %) and being choosy with food (74 %). Children who were introduced to solids ≥6 months had a lower risk of feeding difficulties (RR 0·73; 95 % CI 0·59, 0·91, P=0·004) than children who were introduced to solids between 4 and 6 months. No other significant associations were found. There were few associations between feeding difficulties in relation to age at introduction of solid foods. However, general feeding difficulties were less common among infants introduced to solid foods ≥6 months of age.

Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey.

INTRODUCTION: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. METHODS: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. RESULTS: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002-0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. DISCUSSION: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.

Diet quality across early childhood and adiposity at 6 years: the Southampton Women's Survey.

BACKGROUND: Poor diet quality in early childhood is inconsistently linked to obesity risk. Understanding may be limited by the use of cross-sectional data and the use of body mass index (BMI) to define adiposity in childhood. OBJECTIVE: The objective of this study is to examine the effects of continued exposure to diets of varying quality across early childhood in relation to adiposity at 6 years. METHODS: One thousand and eighteen children from a prospective UK birth cohort were studied. Diet was assessed using food frequency questionnaires when the children were aged 6 and 12 months, and 3 and 6 years; diet quality was determined according to scores for a principal component analysis-defined dietary pattern at each age (characterized by frequent consumption of fruits, vegetables and fish). At each age, children were allocated a value of 0/1/2 according to third of the distribution (bottom/middle/top) their diet quality score was in; values were summed to calculate an overall diet quality index (DQI) for early childhood (range 0-8). Obesity outcomes considered at 6 years were dual-energy X-ray absorptiometry-assessed fat mass and BMI. RESULTS: One hundred and seven (11%) children had a DQI=0, indicating a consistently low diet quality, 339 (33%) had a DQI=1-3, 378 (37%) had a DQI=4-6 and 194 (19%) had a DQI=7-8. There was a strong association between lower DQI and higher fat mass z-score at 6 years that was robust to adjustment for confounders (fat mass s.d. per 1-unit DQI increase: ß=-0.05 (95% confidence interval (CI): -0.09, -0.01), P=0.01). In comparison with children who had the highest diet quality (DQI=7-8), this amounted to a difference in fat mass of 14% (95% CI: 2%, 28%) at 6 years for children with the poorest diets (DQI=0). In contrast, no independent associations were observed between DQI and BMI. CONCLUSIONS: Continued exposure to diets of low quality across early childhood is linked to adiposity at the age of 6 years.

Body size and body composition: a comparison of children in India and the UK through infancy and early childhood.

BACKGROUND: Indian babies are characterised by the 'thin-fat phenotype' which comprises a 'muscle-thin but adipose' body composition compared with European babies. This body phenotype is of concern because it is associated with an increased risk of diabetes and cardiovascular disease. We examined whether the 'thin-fat phenotype' persists through early childhood, comparing Indian children with white Caucasians in the UK at birth, infancy and childhood, using comparable measurement protocols. METHODS: We used data from two cohorts, the Pune Maternal Nutrition Study (N=631) and the Southampton Women's Survey (N=2643). Measurements of weight, head circumference, mid-upper arm circumference, height, triceps and subscapular skinfold thickness were compared at birth, 1, 2, 3 and 6 years of age. SD scores were generated for the Pune children, using the Southampton children as a reference. Generalised estimating equations were used to examine the changes in SD scores across the children's ages. RESULTS: The Indian children were smaller at birth in all body measurements than the Southampton children and became relatively even smaller from birth to 2 years, before 'catching up' to some extent at 3 years, and more so by 6 years. The deficit for both skinfolds was markedly less than for other measurements at all ages; triceps skinfold showed the least difference between the two cohorts at birth, and subscapular skinfold at all ages after birth. CONCLUSIONS: The 'thin-fat phenotype' previously found in Indian newborns, remains through infancy and early childhood. Despite being shorter and lighter than UK children, Indian children are relatively adipose.

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.

Physical activity, calcium intake and childhood bone mineral: a population-based cross-sectional study.

UNLABELLED: In a free-living cohort of 4-year old children, mean daily time in moderate-vigorous physical activity and daily calcium intake at 3 years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966 mg/day). INTRODUCTION: We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density. METHODS: Children aged 4 years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days. RESULTS: Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R(2) = 3%, p < 0.001), BMC (R(2) = 4%, p < 0.001), aBMD (R (2) = 3%, p = 0.001) and estimated vBMD (R(2) = 2%, p = 0.01), but not height (r (s) = 0.04, p = 0.42) or weight (r(s) = 0.01, p = 0.76). Mean daily calcium intake (assessed at 3 years old) positively predicted bone indices in those with a calcium intake below the median (966 mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p = 0.1) and above median was 6% (p = 0.001). CONCLUSIONS: These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.

Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast.

Fetal growth depends on placental transfer of amino acids from maternal to fetal blood. The mechanisms of net amino acid efflux across the basal membrane (BM) of the placental syncytiotrophoblast to the fetus, although vital for amino acid transport, are poorly understood. We examined the hypothesis that facilitated diffusion by the amino acid transporters TAT1, LAT3 and LAT4 plays an important role in this process, with possible effects on fetal growth. Amino acid transfer was measured in isolated perfused human placental cotyledons (n = 5 per experiment) using techniques which distinguish between different transport processes. Placental TAT1, LAT3 and LAT4 proteins were measured, and mRNA expression levels (measured using real-time quantitative-PCR) were related to fetal and neonatal anthropometry and dual-energy X-ray absorptiometry measurements of neonatal lean mass in 102 Southampton Women's Survey (SWS) infants. Under conditions preventing transport by amino acid exchangers, all amino acids appearing in the fetal circulation were substrates of TAT1, LAT3 or LAT4. Western blots demonstrated the presence of TAT1, LAT3 and LAT4 in placental BM preparations. Placental TAT1 and LAT3 mRNA expression were positively associated with measures of fetal growth in SWS infants (P < 0.05). We provide evidence that the efflux transporters TAT1, LAT3 and LAT4 are present in the human placental BM, and may play an important role in the net efflux of amino acids to the fetus. Unlike other transporters they can increase fetal amino acid concentrations. Consistent with a role in placental amino acid transfer capacity and fetal growth TAT1 and LAT3 mRNA expression showed positive associations with infant size at birth.

The relationship between infant lung function and the risk of wheeze in the preschool years.

RATIONALE: There is evidence that perinatal lung development predicts childhood wheeze. However, very few studies have examined whether preschool wheeze is associated with lower premorbid lung function in early infancy, and as yet there is no information relating atopic and non-atopic preschool wheeze to early lung development. OBJECTIVE: To examine the association between premorbid infant lung function and preschool wheeze, and to explore associations with atopic and non-atopic wheeze phenotypes. METHODS: Infant lung function was measured in 147 healthy term infants aged 5-14 weeks. Rapid thoracoabdominal compression was performed during tidal breathing and at raised volume to measure maximal expiratory flow at functional residual capacity (V' max FRC) and forced expiratory volume in 0.4 sec (FEV(0.4)). Atopic status was determined by skin prick testing at 3 years and wheeze ascertained from parental questionnaires (1 and 3 years). MEASUREMENTS AND MAIN RESULTS: Lower early infancy V' max FRC was associated with wheeze in both the first and third years of life (P=0.002 and 0.006, respectively). Lower early infancy FEV(0.4) was associated with wheeze in the first year (P=0.03). Compared to non-atopic children who did not wheeze, non-atopic children who wheezed in their third year of life had lower FEV(0.4) (P=0.02), while FEV(0.4) values of atopic children who wheezed were not significantly different (P=0.4). CONCLUSIONS: Lower premorbid infant lung function was present in infants who subsequently wheezed during the first and third years of life. Lower FEV(0.4) in early infancy was associated with non-atopic wheeze but not atopic wheeze at 3 years of age.

Maternal muscle mass may influence system A activity in human placenta.

During pregnancy, nutrient partitioning between the mother and fetus must balance promoting fetal survival and maintaining nutritional status of the mother for her health and future fertility. The nutritional status of the pregnant woman, reflected in her body composition, may affect placental function with consequences for fetal development. We investigated the relationship between maternal body composition and placental system A amino acid transporter activity in 103 term placentas from Southampton Women's Survey pregnancies. Placental system A activity was measured as Na(+)-dependent uptake of 10 mumol/L (14)C-methylaminoisobutyric acid (a system A specific amino acid analogue) in placental villous fragments. Maternal body composition was measured at enrollment pre-pregnancy; in 45 infants neonatal body composition was measured using dual-energy x-ray absorptiometry. Term placental system A activity was lower in women with smaller pre-pregnancy upper arm muscle area (r = 0.27, P = 0.007), but was not related to maternal fat mass. System A activity was lower in mothers who reported undertaking strenuous exercise (24.6 vs 29.7 pmol/mg/15 min in sedentary women, P = 0.03), but was not associated with other maternal lifestyle factors. Lower placental system A activity in women who reported strenuous exercise and had a lower arm muscle area may reflect an adaptation in placental function which protects maternal resources in those with lower nutrient reserves. This alteration may affect fetal development, altering fetal body composition, with long-term consequences.

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.

Development of a 20-item food frequency questionnaire to assess a 'prudent' dietary pattern among young women in Southampton.

OBJECTIVE: To develop a short food frequency questionnaire (FFQ) that can be used among young women in Southampton to assess compliance with a prudent dietary pattern characterized by high consumption of wholemeal bread, fruit and vegetables, and low consumption of sugar, white bread, and red and processed meat. METHODS: Diet was assessed using a 100-item interviewer-administered FFQ in 6129 non-pregnant women aged 20-34 years. In total, 94 of these women were re-interviewed 2 years later using the same FFQ. Subsequently, diet was assessed in 378 women attending SureStart Children's Centres in the Nutrition and Well-being Study (NWS) using a 20-item FFQ. The 20 foods included were those that characterized the prudent dietary pattern. RESULTS: The 20-item prudent diet score was highly correlated with the full 100-item score (r=0.94) in the Southampton Women's Survey (SWS). Both scores were correlated with red blood cell folate (r=0.28 for the 100-item score and r=0.25 for the 20-item score). Among the women re-interviewed after 2 years, the change in prudent diet score was correlated with change in red cell folate for both the 20-item (r(S)=0.31) and 100-item scores (r(S)=0.32). In the NWS a strong association between the 20-item prudent diet score and educational attainment (r=0.41) was observed, similar to that seen in the SWS (r=0.47). CONCLUSIONS: The prudent diet pattern describes a robust axis of variation in diet. A 20-item FFQ based on the foods that characterize the prudent diet pattern has clear advantages in terms of time and resources, and is a helpful tool to characterize the diets of young women in Southampton.