Cognitive function and skeletal size and mineral density at age 6-7 years: Findings from the Southampton Women's Survey.

INTRODUCTION: Poor cognitive function and osteoporosis commonly co-exist in later life. In women, this is often attributed to post-menopausal estrogen loss. However, a common early life origin for these conditions and the associations between cognitive function and bone mineral density (BMD) in childhood have not previously been explored. We examined these relationships at age 6-7 years in the Southampton Women's Survey (SWS) mother-offspring cohort. METHODS: Child occipitofrontal circumference (OFC), a proxy for brain volume, intelligence quotient (IQ) [Wechsler Abbreviated Scale of Intelligence] and visual recognition and working memory [CANTAB® Delayed Matching to Sample (DMS) and Spatial Span Length (SSP), respectively] were assessed. Whole-body-less-head (WBLH) and lumbar spine dual-energy X-ray absorptiometry [Hologic Discovery] (DXA) were performed to measure bone area (BA), bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Linear regression was used to examine associations between age and sex standardized variables (ß represent standard deviation (SD) difference per SD of cognitive function). RESULTS: DXA was performed in 1331 children (mean (SD) age 6.8 (0.33) years, 51.5 % male), with OFC, IQ, DMS and SSP assessed in 1250, 551, 490 and 460, respectively. OFC (ß = 0.25 SD/SD, 95%CI 0.20,0.30), IQ (ß = 0.11 SD/SD, 95%CI 0.02,0.19), and DMS (ß = 0.11, SD/SD, 95%CI 0.01,0.20) were positively associated with WBLH BA, with similar associations for lumbar spine BA. OFC and DMS were also positively associated with WBLH BMC, but only OFC was associated with BMD (WBLH: ß = 0.38 SD/SD, 95%CI 0.33,0.43; LS: ß = 0.19 SD/SD, 95%CI 0.13,0.24). CONCLUSION: Childhood brain volume was positively associated with measures of skeletal size and BMD, whereas IQ and memory were associated only with skeletal size. These findings suggest that common early life determinants for skeletal growth and BMD and cognitive function should be explored to identify potential early-life approaches to preventing osteoporosis and cognitive decline.

Blood pressure measurement and adverse pregnancy outcomes: A cohort study testing blood pressure variability and alternatives to 140/90 mmHg.

OBJECTIVE: To examine the association with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit-to-visit BP variability (BPV), adjusted for BP level. DESIGN: An observational study. SETTING: Analysis of data from the population-based UK Southampton Women's Survey (SWS). POPULATION OR SAMPLE: 3003 SWS participants. METHODS: Generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV] and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below. MAIN OUTCOME MEASURES: Gestational hypertension, severe hypertension, pre-eclampsia, preterm birth (PTB), small-for-gestational-age (SGA) infants, neonatal intensive care unit (NICU) admission. RESULTS: A median of 11 BP measurements were included per participant. For BP at ≥20 weeks' gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90 mmHg was a good rule-out test (negative LR <0.20) for pre-eclampsia and BP ≥140/90 mmHg a good rule-in test (positive LR >8.00) for the condition. BP ≥160/110 mmHg could rule-in PTB, SGA infants and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre-eclampsia, PTB, SGA and NICU admission (adjusted RRs 1.05-1.39). CONCLUSIONS: While our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes.

Activity Behaviors Before and During Pregnancy Are Associated With Women's Device-Measured Physical Activity and Sedentary Time in Later Parenthood: A Longitudinal Cohort Analysis.

PURPOSE: To explore how activity behaviors before/during pregnancy relate to those in later parenthood, we assessed associations between sitting and moderate-/strenuous exercise before/during pregnancy, and sedentary time (SED) and moderate to vigorous physical activity (MVPA) 4-7 years postpartum ("later parenthood"). METHODS: Longitudinal data were from the Southampton Women's Survey, United Kingdom. Women reported time spent sitting (in hours per day), in moderate-strenuous exercise (hours per week), and in strenuous exercise (hours per week) at 3 time points before/during pregnancy (ie, preconception, at ∼12-wk and ∼34-wk gestation). From this, we derived 3 behavior trajectories for each woman. In later parenthood, women wore an accelerometer for ≤7 days (mean: 5.4 [SD: 1.8] d), which we used to derive 2 outcomes: minutes per day SED and in MVPA. Multilevel linear regression was used to explore associations between trajectories before/during pregnancy and device-measured SED/MVPA in later parenthood. RESULTS: A total of 780 women provided valid data before/during pregnancy and in later parenthood. Consistent high sitters (vs low) were more sedentary 4-7 years postpartum (ß = 39.5 min/d [95% confidence interval, 23.26 to 55.82]), as were women in groups who sat more in later pregnancy. Consistently high moderate/-strenuous exercisers (vs low) were 22% (95% confidence interval, 2%-47%) more active in later parenthood; those engaging in strenuous activity preconception tended to have higher MVPA as parents. CONCLUSIONS: Trajectories of sitting and exercise before/during pregnancy are associated with SED and MVPA, respectively, in later parenthood. Interventions to reduce sitting in pregnancy and to encourage higher intensity activity preconception may benefit maternal and child health.

Longitudinal dietary trajectories from pregnancy to 3 years post delivery in women with obesity: relationships with adiposity.

OBJECTIVE: The study aim was to examine the relationships between longitudinal dietary trajectories from early pregnancy to 3 years post delivery and adiposity measures in women with obesity. METHODS: The diets of 1208 women with obesity in the UPBEAT (UK Pregnancy Better Eating and Activity Trial) study were assessed using a food frequency questionnaire (FFQ) at 15+0 to 18+6 weeks' gestation (baseline), 27+0 to 28+6 weeks' gestation, and 34+0 to 36+0 weeks' gestation, as well as 6 months and 3 years post delivery. Using factor analysis of the baseline FFQ data, four dietary patterns were identified: fruit & vegetable, African/Caribbean, processed, and snacking. The baseline scoring system was applied to the FFQ data at the four subsequent time points. Group-based trajectory modeling was used to extract longitudinal dietary pattern trajectories. Using adjusted regression, associations between dietary trajectories and log-transformed/standardized adiposity measures (BMI and waist and mid-upper arm circumferences) at 3 years post delivery were examined. RESULTS: Two trajectories were found to best describe the data for the four individual dietary patterns; these were characterized as high and low adherence. A high adherence to the processed pattern was associated with a higher BMI (ß = 0.38 [95% CI: 0.06-0.69]) and higher waist (ß = 0.35 [0.03-0.67]) and mid-upper arm circumferences (ß = 0.36 [0.04-0.67]) at 3 years post delivery. CONCLUSIONS: In women with obesity, a processed dietary pattern across pregnancy and 3 years post delivery is associated with higher adiposity.

Parent-Offspring Associations in Body Composition: Findings From the Southampton Women's Survey Prospective Cohort Study.

CONTEXT: Children born to parents who are overweight or obese have a high risk of adult obesity, but it is unclear if transgenerational associations relating to unfavorable body composition differ by parent. OBJECTIVE: To examine differential mother-offspring and father-offspring associations in body composition in early childhood. METHODS: A total of 240 mother-father-offspring trios from a prospective UK population-based pre-birth cohort (Southampton Women's Survey) were included for anthropometry and dual-energy x-ray absorptiometry assessment of whole-body-less-head body composition in the offspring at 3 different ages (4, 6-7, and 8-9 years) and in the mother and father at the 8- to 9-year offspring visit. Associations were assessed using linear regression adjusting for the other parent. RESULTS: Positive associations between mother-daughter body mass index (BMI) and fat mass were observed at ages 6 to 7 (BMI: ß = .29 SD/SD, 95% CI = .10, .48; fat mass ß = .27 SD/SD, 95% CI = .05, .48) and 8 to 9 years (BMI: ß = .33 SD/SD, 95% CI = .13, .54; fat mass ß = .31 SD/SD, 95% CI = .12, .49), with similar associations at age 4 years but bounding the 95% CI. The mother-son, father-son, and father-daughter associations for BMI and fat mass were weaker at each of the ages studied. CONCLUSION: A strong association between the fat mass of mothers and their daughters but not their sons was observed. In contrast, father-offspring body composition associations were not evident. The dimorphic parent-offspring effects suggest particular attention should be given to early prevention of unfavorable body composition in girls born to mothers with excess adiposity.

Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? Post hoc analyses of the MAVIDOS randomized controlled trial.

BACKGROUND: Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH). METHODS: MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks' gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500 ml estimated blood loss) were determined from medical records. RESULTS: A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode. CONCLUSIONS: Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD.

Evaluation and interpretation of latent class modelling strategies to characterise dietary trajectories across early life: a longitudinal study from the Southampton Women's Survey.

There is increasing interest in modelling longitudinal dietary data and classifying individuals into subgroups (latent classes) who follow similar trajectories over time. These trajectories could identify population groups and time points amenable to dietary interventions. This paper aimed to provide a comparison and overview of two latent class methods: group-based trajectory modelling (GBTM) and growth mixture modelling (GMM). Data from 2963 mother-child dyads from the longitudinal Southampton Women's Survey were analysed. Continuous diet quality indices (DQI) were derived using principal component analysis from interviewer-administered FFQ collected in mothers pre-pregnancy, at 11- and 34-week gestation, and in offspring at 6 and 12 months and 3, 6-7 and 8-9 years. A forward modelling approach from 1 to 6 classes was used to identify the optimal number of DQI latent classes. Models were assessed using the Akaike and Bayesian information criteria, probability of class assignment, ratio of the odds of correct classification, group membership and entropy. Both methods suggested that five classes were optimal, with a strong correlation (Spearman's = 0·98) between class assignment for the two methods. The dietary trajectories were categorised as stable with horizontal lines and were defined as poor (GMM = 4 % and GBTM = 5 %), poor-medium (23 %, 23 %), medium (39 %, 39 %), medium-better (27 %, 28 %) and best (7 %, 6 %). Both GBTM and GMM are suitable for identifying dietary trajectories. GBTM is recommended as it is computationally less intensive, but results could be confirmed using GMM. The stability of the diet quality trajectories from pre-pregnancy underlines the importance of promotion of dietary improvements from preconception onwards.

The association between number and ages of children and the physical activity of mothers: Cross-sectional analyses from the Southampton Women's Survey.

BACKGROUND: Physical activity (PA) has many health benefits, but motherhood is often associated with reduced PA. Considering that ages and number of children may be associated with maternal PA, and that PA patterns may change as children transition to formal schooling, we aimed to investigate the associations between ages and number of children and device-measured maternal PA. METHODS: Cross-sectional analyses were conducted using data from 848 mothers from the Southampton Women's Survey at two different timepoints. Two-level random intercept linear models were used to investigate associations between ages (≤4y(ears) ("younger"), school-aged, both age groups) and number (1, 2, ≥3) of children, and their interaction, and accelerometer-assessed minutes of maternal moderate or vigorous PA (log-transformed MVPA) and light, moderate or vigorous PA (LMVPA). RESULTS: Women with any school-aged children engaged in more MVPA than those with only ≤4y (e.g. % difference in minutes of MVPA [95% confidence interval]: 46.9% [22.0;77.0] for mothers with only school-aged vs only ≤4y). Mothers with multiple children did less MVPA than those with 1 child (e.g. 12.5% [-1.1;24.3] less MVPA for those with 2 children). For mothers with multiple children, those with any school-aged children did less LMVPA than those with only ≤4y (e.g. amongst mothers with 2 children, those with only school-aged children did 34.0 [3.9;64.1] mins/day less LMVPA). For mothers with any ≤4y, those with more children did more LMVPA (e.g. amongst mothers with only ≤4y, those with 2 children did 42.6 [16.4;68.8] mins/day more LMVPA than those with 1 child). CONCLUSIONS: Mothers with multiple children and only children aged ≤4y did less MVPA. Considering that many of these women also did more LMVPA than mothers with fewer or older children, interventions and policies are needed to increase their opportunities for higher intensity PA to maximise health benefits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04715945.

Early-onset burdensome multimorbidity: an exploratory analysis of sentinel conditions, condition accrual sequence and duration of three long-term conditions using the 1970 British Cohort Study.

OBJECTIVES: The prevalence of multiple long-term condition (LTC) multimorbidity is increasing with younger onset among socioeconomically deprived populations. Research on life course trajectories towards multimorbidity is limited and early-onset multimorbidity poorly characterised. Understanding sentinel conditions (the first LTC occurring in the life course), the sequence of LTC accrual and the permanency of the reporting of LTCs may help identify time points for prevention efforts. We used a longitudinal birth cohort to estimate the prevalence of a common three-condition early-onset multimorbidity (multiple long-term condition multimorbidity (MLTC-M)) group at midlife, describe the frequency of sentinel conditions, the sequence of LTC accrual and explore the permanency of one of these conditions: psychological distress. SETTING: 1970 British Cohort Study (BCS70). PARTICIPANTS: 17 196 cohort members born in 1970. OUTCOME MEASURES: Prevalence of the most common three-condition multimorbidity group at age 46. The nature and timing of sentinel conditions, the sequencing patterns of subsequent LTC accrual and the permanency of the reporting of psychological distress. RESULTS: At age 46 high blood pressure, psychological distress and back pain were the most common three-condition MLTC-M group, (4.3%, n=370). A subgroup of 164 (44.3%) people provided complete information on LTC across all time points. Psychological distress measured by the Malaise Index was the most common sentinel condition, occurring in 25.0% (n=41), followed by back pain (22%, n=36). At age 26, 45.1% (75/164) reported their sentinel condition. The most common sequence of LTC accrual was the co-reporting of psychological distress and back pain followed by high blood pressure. Almost one-third (30.5%, n=50) reported a variation of psychological distress across the adult life course. CONCLUSION: In these exploratory analyses, psychological distress and back pain were the most common sentinel conditions, and along with high blood pressure these three conditions represented the most common three-condition MLTC-M group. These analyses suggest that birth cohorts, like the BCS70, may usefully inform life course-multimorbidity research.

Predictors of maternal dietary quality and dietary inflammation during pregnancy: An individual participant data meta-analysis of seven European cohorts from the ALPHABET consortium.

BACKGROUND & AIMS: Maternal diet during pregnancy is a modifiable behaviour which plays an important role in maternal, neonatal and child health outcomes. Thus, knowledge of predictors of dietary quality and dietary inflammatory potential in European countries may contribute to developing maternal diet-related public health policies that target specific at-risk populations in Europe. METHODS: We used harmonised data from >26,000 pregnant women enrolled in the ALSPAC, EDEN, Generation R, Lifeways, REPRO_PL, ROLO and SWS cohorts, as part of the ALPHABET consortium. Maternal dietary quality and inflammatory potential were assessed using the Dietary Approaches to Stop Hypertension (DASH) and the energy-adjusted Dietary Inflammatory Index (E-DII). We conducted an individual participant data meta-analysis to investigate the maternal sociodemographic, health and behavioural predictors of maternal diet before and during pregnancy. RESULTS: DASH and E-DII scores were moderately correlated: from -0.63 (95% CI: -0.66, -0.59) to -0.48 (95% CI: -0.49, -0.47) across cohorts. Higher maternal age, education, household income, and physical activity during pregnancy were associated with a better dietary quality and a more anti-inflammatory diet. Conversely, multiparity and smoking during pregnancy were associated with a poorer dietary quality and a more proinflammatory diet. Women with obesity had a poorer pregnancy dietary quality than women with a normal body mass index range. CONCLUSIONS: The results will help identify population subgroups who may benefit from targeted public health strategies and interventions aimed at improving women's dietary quality during pregnancy.

Pregnancy Vitamin D Supplementation and Childhood Bone Mass at Age 4 Years: Findings From the Maternal Vitamin D Osteoporosis Study (MAVIDOS) Randomized Controlled Trial.

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/L from three research centers (2008-2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013-2018). Anthropometry and dual-energy X-ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472-0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466-0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age- and sex-adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Activity Behaviors in British 6-Year-Olds: Cross-Sectional Associations and Longitudinal Change During the School Transition.

BACKGROUND: To explore activity behaviors at school entry, we describe temporal/demographic associations with accelerometer-measured physical activity in a population-based sample of British 6-year-olds, and examine change from ages 4 to 6. METHODS: A total of 712 six-year-olds (308 at both ages) wore Actiheart accelerometers for ≥3 (mean 6.0) days. We derived minutes per day sedentary (<20 cpm) and moderate to vigorous physical activity (MVPA, ≥460 cpm), also segmented across mornings (06:00 AM to 09:00 AM), school (09:00 AM to 3:00 PM), and evenings (3:00 PM to 11:00 PM). Using mixed effects linear regression, we analyzed associations between temporal/demographic factors and children's activity intensities at age 6, and change between ages 4 and 6. RESULTS: Six-year-old children engaged in MVPA (mean [SD]): 64.9 (25.7) minutes per day (53% met UK guidelines). Girls did less MVPA than boys, particularly during school hours. Children were less active on weekends (vs weekdays) and more active on spring/summer evenings (vs winter). Longitudinally, 6-year-old children did less light physical activity (-43.0; 95% confidence interval, -47.5 to -38.4 min/d) but were more sedentary (29.4; 24.6 to 34.2), and engaged in greater MVPA (7.1; 5.2 to 9.1) compared to when they were aged 4. CONCLUSION: Half of 6-year-old children met current activity guidelines; MVPA levels were lower in girls and at weekends. UK children became more sedentary but did more MVPA as they entered formal schooling. Physical activity promotion efforts should capitalize on these changes in MVPA, to maintain positive habits.

Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial.

BACKGROUND: Evidence linking prenatal maternal vitamin D supplementation with the offspring's risk of atopic eczema is inconsistent, with most data coming from observational studies. OBJECTIVES: To examine the influence of maternal cholecalciferol supplementation during pregnancy on the risk of atopic eczema in the offspring at ages 12, 24 and 48 months. METHODS: Within the UK Maternal Vitamin D Osteoporosis Study (MAVIDOS) double-blind, randomized placebo-controlled trial, we examined the relationship of maternal vitamin D supplementation during pregnancy with offspring atopic eczema at ages 12, 24 and 48 months. In MAVIDOS, pregnant women were allocated to either cholecalciferol 1000 IU per day or matched placebo, taken from around 14 weeks' gestation until delivery, with the primary outcome of neonatal whole-body bone mineral content. The prevalence of atopic eczema in the offspring was ascertained at ages 12 (n = 635), 24 (n = 610) and 48 (n = 449) months, based on the UK Working Party criteria for the definition of atopic dermatitis. The trial was registered with ISRCTN (82927713) and EudraCT (2007-001716-23). RESULTS: The characteristics of mothers and offspring were similar between the intervention and placebo groups, apart from longer breastfeeding duration in the intervention group. Adjusting for breastfeeding duration, offspring of mothers who received cholecalciferol 1000 IU daily had a lower odds ratio (OR) of atopic eczema at age 12 months [OR 0·55, 95% confidence interval (CI) 0·32-0·97, P = 0·04]; this effect weakened and was not statistically significant at ages 24 months (OR 0·76, 95% CI 0·47-1·23) or 48 months (OR 0·75, 95% CI 0·37-1·52). The statistical interaction of intervention and breastfeeding duration in relation to eczema at age 12 months was not significant (P = 0·41), but stratification showed reduced infantile eczema risk in the intervention group for infants breastfed for ≥ 1 month (OR 0·48, 95% CI 0·24-0·94, P = 0·03) but not in those breastfed for < 1 month (OR 0·80, 95% CI 0·29-2·17, P = 0·66). CONCLUSIONS: Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on the risk of infantile atopic eczema, with the effect potentially being via increased breast milk cholecalciferol levels. The findings support a developmental influence on atopic eczema, and point to a potentially modifiable perinatal influence on atopic eczema. What is already known about this topic? There are currently no antenatal interventions proven to reduce the incidence of infantile atopic eczema in the general population. However, observational studies have led to speculation that antenatal vitamin D supplementation may be beneficial.

Associations Between Late Pregnancy Dietary Inflammatory Index (DII) and Offspring Bone Mass: A Meta-Analysis of the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC).

Systemic inflammation is associated with reduced bone mineral density and may be influenced by pro-inflammatory diets. We undertook an observational analysis of associations between late pregnancy energy-adjusted dietary inflammatory index (E-DII) scores and offspring bone outcomes in childhood. E-DII scores (higher scores indicating pro-inflammatory diets) were derived from food frequency questionnaires in late pregnancy in two prospective mother-offspring cohorts: the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). The mean (SD) offspring age at dual-energy X-ray absorptiometry (DXA) scanning was 9.2 (0.2) years. Linear regression was used to assess associations between E-DII and bone outcomes, adjusting for offspring sex and age at DXA and maternal age at childbirth, educational level, pre-pregnancy body mass index (BMI), parity, physical activity level, and smoking in pregnancy. Associations were synthesized using fixed-effect meta-analysis. Beta coefficients represent the association per unit E-DII increment. In fully adjusted models (total n = 5910) late pregnancy E-DII was negatively associated with offspring whole body minus head bone area (BA: ß = -3.68 [95% confidence interval -6.09, -1.27] cm2 /unit), bone mineral content (BMC: ß = -4.16 [95% CI -6.70, -1.62] g/unit), and areal bone mineral density (aBMD: ß = -0.0012 [95% CI -0.0020, -0.0004] g.cm-2 /unit), but there was only a weak association with BMC adjusted for BA (ß = -0.48 [95% CI -1.11, 0.15] g/unit) at 9 years. Adjustment for child height partly or, for weight, fully attenuated the associations. Higher late pregnancy E-DII scores (representing a more pro-inflammatory diet) are negatively associated with offspring bone measures, supporting the importance of maternal and childhood diet on longitudinal offspring bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Peri-conceptional diet patterns and the risk of Gestational diabetes mellitus in South Indian women.

OBJECTIVE: To identify peri-conceptional diet patterns among women in Bangalore, and examine their associations with risk of gestational diabetes mellitus. DESIGN: BANGLES, started in June 2016, was a prospective observational study, in which women were recruited at 5-16 weeks' gestation. Peri-conceptional diet was recalled at recruitment, using a validated 224-item food frequency questionnaire. GDM was assessed by a 75-gram oral glucose tolerance test at 24-28 weeks' gestation, applying WHO 2013 criteria. Diet patterns were identified using principal component analysis and diet pattern-GDM associations were examined using multivariate logistic regression, adjusting for 'a priori' confounders. SETTING: Antenatal clinics of two hospitals, Bangalore, South India. PARTICIPANTS: 785 pregnant women of varied socio-economic status. RESULTS: GDM prevalence was 22%. Three diet patterns were identified: a) High-diversity, urban (HDU) characterised by diverse, home-cooked and processed foods was associated with older, more affluent, better-educated and urban women; b) Rice-fried snacks-chicken-sweets (RFCS), characterised by low diet-diversity, was associated with younger, less-educated, and lower income, rural and joint families; c) Healthy, traditional vegetarian (HTV), characterised by home-cooked-vegetarian and non-processed foods was associated with less-educated, more affluent, and rural and joint families. The HDU pattern was associated with a lower GDM risk (aOR: 0.80 per SD, 95% CI: 0.64, 0.99, p=0.04) after adjusting for confounders. BMI was strongly related to GDM risk and possibly mediated diet-GDM associations. CONCLUSIONS: The findings support global recommendations to encourage women to attain a healthy pre-pregnancy BMI and increase diet-diversity. Both healthy and unhealthy foods in the patterns indicate low-awareness about healthy foods and a need for public-education.

Is the skull responsive to bone mineralisation stimuli in children?

BACKGROUND: Whole-body-less-head (WBLH) is the recommended skeletal region of interest (ROI) for dual-energy X-ray absorptiometry (DXA) assessment of bone mineral density (BMD) in children. Historically it has been suggested that the skull is less responsive than the rest of the skeleton to stimuli that affect BMD but there are few published data to support this notion. We compared the associations of BMD with anthropometric, body composition, diet, and activity variables across various ROI. METHODS: Children from the Southampton Women's Survey (SWS) mother-offspring cohort participated at age 6-7 years, including measurement of height, weight, and whole-body and lumbar spine (LS) BMD by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart) and diet by interviewer-led questionnaire. BMD was measured in the following skeletal ROI: whole-body, skull, WBLH and lower limbs (all derived from the whole-body scan) and LS. RESULTS: 1218 children participated. Height z-score, weight z-score, lean mass and milk intake were associated with skull BMD, but associations were weaker than observed for other ROI; for example, the association between lean mass and skull BMD was ß (95% CI) 0.11 (0.08, 0.14) SD/kg, compared with 0.32 (0.30, 0.34), 0.38 (0.37, 0.40) and 0.23 (0.21, 0.25) SD/kg for whole body, WBLH and lumbar spine, respectively. Relationships with whole-body BMD were attenuated compared with WBLH. CONCLUSION: Associations between skull BMD and anthropometry, body composition and dietary variables were weaker than for other DXA sites. These findings support, and importantly provide a quantitative basis for, the recommendation that the skull should be excluded from whole-body DXA analyses in children.

Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit.

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.

Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children.

RATIONALE: Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health. METHODS: We performed an individual participant meta-analysis among 18 326 mother-child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry. RESULTS: After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference -0.05, 95% CI -0.08- -0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <-1.64) (OR 1.20, 95% CI 1.06-1.36 and z-score difference 1.40, 95% CI 1.06-1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively. CONCLUSION: The main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Longitudinal dietary trajectories from preconception to mid-childhood in women and children in the Southampton Women's Survey and their relation to offspring adiposity: a group-based trajectory modelling approach.

BACKGROUND: Rates of childhood obesity are increasing globally, with poor dietary quality an important contributory factor. Evaluation of longitudinal diet quality across early life could identify timepoints and subgroups for nutritional interventions as part of effective public health strategies. OBJECTIVE: This research aimed to: (1) define latent classes of mother-offspring diet quality trajectories from pre-pregnancy to child age 8-9 years, (2) identify early life factors associated with these trajectories, and (3) describe the association between the trajectories and childhood adiposity outcomes. DESIGN: Dietary data from 2963 UK Southampton Women's Survey mother-offspring dyads were analysed using group-based trajectory modelling of a diet quality index (DQI). Maternal diet was assessed pre-pregnancy and at 11- and 34-weeks' gestation, and offspring diet at ages 6 and 12 months, 3, 6-7- and 8-9-years using interviewer-administered food frequency questionnaires. At each timepoint, a standardised DQI was derived using principal component analysis. Adiposity age 8-9 years was assessed using dual-energy X-ray absorptiometry (DXA) and BMI z-scores. RESULTS: A five-trajectory group model was identified as optimal. The diet quality trajectories were characterised as stable, horizontal lines and were categorised as poor (n = 142), poor-medium (n = 667), medium (n = 1146), medium-better (n = 818) and best (n = 163). A poorer dietary trajectory was associated with higher maternal pre-pregnancy BMI, smoking, multiparity, lower maternal age and lower educational attainment. Using linear regression adjusted for confounders, a 1-category decrease in the dietary trajectory was associated with higher DXA percentage body fat (0.08 SD (95% confidence interval 0.01, 0.15) and BMI z-score (0.08 SD (0.00, 0.16) in the 1216 children followed up at age 8-9 years. CONCLUSION: Mother-offspring dietary trajectories are stable across early life, with poorer diet quality associated with maternal socio-demographic and other factors and childhood adiposity. The preconception period may be an important window to promote positive maternal dietary changes in order to improve childhood outcomes.