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Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Context Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long-term outcomes and adult body composition in SRS are limited. Objective To evaluate body composition and metabolic health in adults with SRS. Methods This was an observational study of 25 individuals with molecularly confirmed SRS, aged ≥ 18 years, from research facilities across the UK. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey [SWS]). Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured. Results Twenty-five adults with SRS were included (52% female). The median age was 32.9 years (range, 22.0 to 69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, P <.001). Fat mass index was similar (9.6 vs 7.8, P =.3). Lean mass percentage (51.8% vs 66.2%, P <.001) and lean mass index (13.5 kg/m2 vs 17.3 kg/m2, P <.001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, P <.001; all median values). Total cholesterol was ≥ 5 mmol/L in 52.0%. Triglyceride levels were ≥ 1.7 mmol/L in 20.8%. Fasting blood glucose levels were ≥ 6.1 mmol/L in 25.0%. Hypertension was present in 33.3%. Conclusion Adults with SRS have an unfavorable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes. [ABSTRACT FROM AUTHOR]

Author(s): Johan L. Vinther, Tim Cadman, Demetris Avraam, Claus T. Ekstrøm, Thorkild I. A. Sørensen, Ahmed Elhakeem, Ana C. Santos, Angela Pinot de Moira, Barbara Heude, Carmen Iñiguez, Costanza Pizzi, [...]

Background Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. Methods and findings We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. Conclusions This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term., Author(s): Johan L. Vinther 1,*, Tim Cadman 2, Demetris Avraam 3, Claus T. Ekstrøm 4, Thorkild I. A. Sørensen 1,5, Ahmed Elhakeem 2, Ana C. Santos 6,7, Angela Pinot de [...]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Trials in developing countries suggest that improving young children's diet may benefit cognitive development. Whether dietary composition influences young children's cognition in developed countries is unclear. Although many studies have examined the relation between type of milk received in infancy and subsequent cognition, there has been no investigation of the possible effect of variations in the weaning diet. Methods: We studied 241 children aged 4 years, whose diet had been assessed at age 6 and 12 months. We measured IQ with the Wechsler Pre-School and Primary Scale of Intelligence, visual attention, visuomotor precision, sentence repetition and verbal fluency with the Developmental Neuropsychological Assessment (NEPSY), and visual form-constancy with the Test of Visual Perceptual Skills. Results: In sex-adjusted analyses, children whose diet in infancy was characterised by high consumption of fruit, vegetables and home-prepared foods ("infant guidelines" dietary pattern) had higher full-scale and verbal IQ and better memory performance at age 4 years. Further adjustment for maternal education, intelligence, social class, quality of the home environment and other potential confounding factors attenuated these associations but the relations between higher "infant guidelines" diet score and full-scale and verbal IQ remained significant. For a standard deviation increase in "infant guidelines" diet score at 6 or 12 months full-scale IQ rose by 0.18 (95% CI 0.04 to 0.31) of a standard deviation. For a standard deviation increase in "infant guidelines" diet score at 6 months verbal IQ rose by 0.14 (0.01 to 0.27) of a standard deviation. There were no associations between dietary patterns in infancy and 4-year performance on the other tests. Conclusions: These findings suggest that dietary patterns in early life may have some effect on cognitive development. It is also possible that they reflect the influence of unmeasured confounding factors. (Contains 4 tables.)