Validating inborn error of immunity prevalence and risk with nationally representative electronic health record data.

BACKGROUND: The 10 Warning Signs of Primary Immunodeficiency were created 30 years ago to advance recognition of inborn errors of immunity (IEI). However, no population-level assessment of their utility applied to electronic health record (EHR) data has been conducted. OBJECTIVE: We sought to quantify the value of having ≥2 warning signs (WS) toward diagnosing IEI using a highly representative real-world US cohort. A secondary goal was estimating the US prevalence of IEI. METHODS: In this cohort study, we accessed normalized and de-identified EHR data on 152 million US patients. An IEI cohort (n = 41,080), in which patients were defined by having at least 1 verifiable IEI diagnosis placed ≥2 times in their record, was compared with a matched set of controls (n = 250,262). WS were encoded along with relevant diagnoses, relative weights were calculated, and the proportion of IEI cases versus controls with ≥2 WS was compared. RESULTS: The proportion of IEI cases with ≥2 WS significantly differed from controls (0.33 vs 0.031; P < .0005, χ2 test). We also estimated a US IEI prevalence of 6 per 10,000 individuals (41,080/73,165,655; 0.056%). WS 9 (≥2 deep-seated infections), 7 (fungal infections), 5 (failure to thrive) and 4 (≥2 pneumonias in 1 year) were the most heavily weighted among the IEI cohort. CONCLUSIONS: This nationally representative US-based cohort study demonstrates that presence of WS and associated clinical diagnoses can facilitate identification of patients with IEI from EHR data. In addition, we estimate that 6 in 10,000, or approximately 150,000 to 200,000 individuals are affected by IEI across the United States.

Hadean silicate differentiation preserved by anomalous 142Nd/144Nd ratios in the Réunion hotspot source.

Active volcanic hotspots can tap into domains in Earth's deep interior that were formed more than two billion years ago. High-precision data on variability in tungsten isotopes have shown that some of these domains resulted from differentiation events that occurred within the first fifty million years of Earth history. However, it has not proved easy to resolve analogous variability in neodymium isotope compositions that would track regions of Earth's interior whose composition was established by events occurring within roughly the first five hundred million years of Earth history. Here we report 142Nd/144Nd ratios for Réunion Island igneous rocks, some of which are resolvably either higher or lower than the ratios in modern upper-mantle domains. We also find that Réunion 142Nd/144Nd ratios correlate with helium-isotope ratios (3He/4He), suggesting parallel behaviour of these isotopic systems during very early silicate differentiation, perhaps as early as 4.39 billion years ago. The range of 142Nd/144Nd ratios in Réunion basalts is inconsistent with a single-stage differentiation process, and instead requires mixing of a conjugate melt and residue formed in at least one melting event during the Hadean eon, 4.56 billion to 4 billion years ago. Efficient post-Hadean mixing nearly erased the ancient, anomalous 142Nd/144Nd signatures, and produced the relatively homogeneous 143Nd/144Nd composition that is characteristic of Réunion basalts. Our results show that Réunion magmas tap into a particularly ancient, primitive source compared with other volcanic hotspots, offering insight into the formation and preservation of ancient heterogeneities in Earth's interior.

Tungsten-182 evidence for an ancient kimberlite source.

Globally distributed kimberlites with broadly chondritic initial 143Nd-176Hf isotopic systematics may be derived from a chemically homogenous, relatively primitive mantle source that remained isolated from the convecting mantle for much of the Earth's history. To assess whether this putative reservoir may have preserved remnants of an early Earth process, we report 182W/184W and 142Nd/144Nd data for "primitive" kimberlites from 10 localities worldwide, ranging in age from 1,153 to 89 Ma. Most are characterized by homogeneous µ182W and µ142Nd values averaging -5.9 ± 3.6 ppm (2SD, n = 13) and +2.7 ± 2.9 ppm (2SD, n = 6), respectively. The remarkably uniform yet modestly negative µ182W values, coupled with chondritic to slightly suprachondritic initial 143Nd/144Nd and 176Hf/177Hf ratios over a span of nearly 1,000 Mya, provides permissive evidence that these kimberlites were derived from one or more long-lived, early formed mantle reservoirs. Possible causes for negative µ182W values among these kimberlites include the transfer of W with low µ182W from the core to the mantle source reservoir(s), creation of the source reservoir(s) as a result of early silicate fractionation, or an overabundance of late-accreted materials in the source reservoir(s). By contrast, two younger kimberlites emplaced at 72 and 52 Ma and characterized by distinctly subchondritic initial 176Hf/177Hf and 143Nd/144Nd have µ182W values consistent with the modern upper mantle. These isotopic compositions may reflect contamination of the ancient kimberlite source by recycled crustal components with µ182W ≥ 0.

Parental Height and Weight Influence Offspring Adiposity at 2 Years; Findings from the ROLO Kids Birth Cohort Study.

OBJECTIVE: The perinatal period and in utero environment are important for fetal growth, development, and fetal programming. This study aimed to determine the effect of parental anthropometry and the maternal metabolic milieu on offspring adiposity at 2 years of age. STUDY DESIGN: This longitudinal birth cohort includes analysis of maternal (n = 337) and paternal (n = 219) anthropometry and maternal and fetal metabolic markers (n = 337), including glucose, homeostatic model of assessment (HOMA), C-peptide, and leptin from participants of the ROLO (the Randomized Control Trial of Low) pregnancy study, and their partners, to determine an association with offspring anthropometry at two years of age. RESULTS: Linear regression, when adjusted for confounders, indicated maternal and paternal anthropometry and was associated with offspring weight and length at 2 years of age. Maternal height was negatively associated with general adiposity in the total cohort of children (p = 0.002) and in female children (p = 0.006) and central adiposity in the total child cohort (p < 0.001). Paternal height was also negatively associated with general adiposity in all children (p = 0.002) and central adiposity in total (p = 0.023) and female children (p = 0.008). Maternal glucose, insulin resistance, and fetal C-peptide positively correlated with anthropometry in total, male, and female children. CONCLUSION: Parental anthropometry in the perinatal period has a long-lasting effect on offspring anthropometry beyond the neonatal period. Maternal and fetal metabolic factors influence adiposity, and this extends beyond the perinatal period. Parental adiposity may play a significant role in early childhood adiposity and may be a target for interventions to decrease the risk of early childhood obesity. KEY POINTS: · Parental height and weight were associated with offspring anthropometry and measures of offspring adiposity at 2 years of age.. · Maternal glucose, insulin resistance, and fetal C-peptide correlated with offspring anthropometry.. · Parental anthropometry has long-term effect on offspring adiposity and is seen at 2 years of age..

Maternal protein intake during pregnancy is associated with child growth up to 5 years of age, but not through insulin-like growth factor-1: findings from the ROLO study.

Infant protein intake has been associated with child growth, however, research on maternal protein intake during pregnancy is limited. Insulin-like growth factors (IGF) play a role in early fetal development and maternal protein intake may influence child body composition via IGF-1. The aim of this study was to investigate the association of maternal protein intake throughout pregnancy on cord blood IGF-1 and child body composition from birth to 5 years of age. Analysis was carried out on 570 mother-child dyads from the Randomised cOntrol trial of LOw glycaemic index diet study. Protein intake was recorded using 3-d food diaries in each trimester of pregnancy and protein intake per kg of maternal weight (g/d per kg) was calculated. Cord blood IGF-1 was measured at birth. Infant anthropometry was measured at birth, 6 months, 2 and 5 years of age. Mixed modelling, linear regression, and mediation analysis were carried out. Birth weight centiles were positively associated with early-pregnancy protein intake (g/d per kg), while weight centiles from 6 months to 5 years were negatively associated (B=-21·6, P<0·05). These associations were not mediated by IGF-1. Our findings suggest that high protein intake in early-pregnancy may exert an in utero effect on offspring body composition with a higher weight initially at birth but slower growth rates into childhood. Further research is needed to elucidate the exact mechanisms by which dietary protein modulates fetal growth.

The association between childcare and risk of childhood overweight and obesity in children aged 5 years and under: a systematic review.

UNLABELLED: The aim of this paper was to systematically review the published evidence on the relationship between the type of childcare and risk of childhood overweight or obesity. The databases PubMed, MEDLINE, Cochrane Library and EMBASE were searched using combinations of the various search terms to identify eligible observational studies published between 2000 and May 2016 in English. Fifteen publications from 7 countries matched the inclusion criteria. The most commonly reported childcare arrangements were centre-based (e.g. crèche) and informal care (e.g. relatives, neighbours, friends). Informal care was most frequently associated with an increased risk of childhood overweight and obesity. Associations were also found for other lifestyle variables such as low maternal education, high birth-weight, maternal employment, ethnicity, maternal overweight/obesity and father's Body Mass Index (BMI). CONCLUSION: The relationship between childcare and childhood overweight/obesity is multi-faceted with many aspects linked to childhood adiposity, in particular the age of initiation to care, type of care (i.e. informal care) and shorter breastfeeding duration were related with infant adiposity. WHAT IS KNOWN: • Lifestyle factors during early years affect health outcomes in adulthood, particularly in children with low birth weight. • Pre-school stage influences children's body composition and growth. What is new: • This is the first systematic review of observational studies examining the association between childcare and childhood overweight and obesity in preschool children. • 'Informal' care is linked to early introduction to solid foods, less physical activity and obesity.

Women growing older with environmental sensitivities: A grounded theory model of meeting one's needs.

This article describes a telephone interview study of 21 women over the age of 65 with environmental sensitivities (ES), including both chemical and electrical hypersensitivities. We employed Charmaz's constructivist grounded theory, using incident, focused, and theoretical coding levels. We were interested in how informants thought their needs would be met as they grew older with ES. We found a central process (that which motivates informants) of "balancing on a changing tightrope with great overwhelm" with three categories: No Safety Net, The Knowing, and Going Through the Cracks. No Safety Net refers to the inaccessibility of most community and health resources for persons who must avoid chemicals, electromagnetic fields, or both. The Knowing refers to having the awareness that one has been dealt out of the equation and will not receive help from conventional sources. Going Through the Cracks describes living one's life by finding small openings and opportunities for living and experiencing what most take for granted. We describe these categories in detail and appeal to health care providers and the general public to view culture through the eyes of those who are unable to participate in it to an extent considered "normal."

The association between maternal dietary micronutrient intake and neonatal anthropometry - secondary analysis from the ROLO study.

BACKGROUND: Micronutrients are necessary for fetal growth. However increasingly pregnant women are nutritionally replete and little is known about the effect of maternal micronutrient intakes on fetal adiposity in mothers with increased BMI. The aim of this study was to examine the association of maternal dietary micronutrient intake with neonatal size and adiposity in a cohort at risk of macrosomia. METHODS: This was a cohort analysis of 554 infants from the ROLO study. Three day food diaries from each trimester were collected. Neonatal weight, length, circumferences and skinfold thicknesses were measured at birth. Multiple linear regression was used to identify associations between micronutrient intakes and neonatal anthropometry. RESULTS: Birthweight was negatively associated with maternal trimester 3 vitamin D intake and positively associated with trimester 3 vitamin B12 intake R2adj 19.8% (F = 13.19, p <0.001). Birth length was positively associated with trimester 3 magnesium intake R2adj 12.9% (F = 8.06, p <0.001). In terms of neonatal central adiposity; abdominal circumference was positively associated with maternal trimester 3 retinol intake and negatively associated with trimester 3 vitamin E and selenium intake R2adj 11.9% (F = 2.93, p = 0.002), waist:length ratio was negatively associated with trimester 3 magnesium intake R2adj 20.1% (F = 3.92, p <0.001) and subscapular:triceps skinfold ratio was negatively associated with trimester 1 selenium intake R2adj7.2% (F = 2.00, p = 0.047). CONCLUSIONS: Maternal micronutrient intake was associated with neonatal anthropometry even in women not at risk of malnutrition. Further research is necessary to determine optimal micronutrient intake in overweight and obese pregnant women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54392969.

Fetal metabolic influences of neonatal anthropometry and adiposity.

BACKGROUND: Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring. METHODS: Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity. RESULTS: Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant. CONCLUSION: Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

Maternal low glycaemic index diet, fat intake and postprandial glucose influences neonatal adiposity--secondary analysis from the ROLO study.

BACKGROUND: The in utero environment is known to affect fetal development however many of the mechanisms by which this occurs remain unknown. The aim of this study was to examine the association between maternal dietary macronutrient intake and lifestyle throughout pregnancy and neonatal weight and adiposity. METHODS: This was an analysis of 542 mother and infant pairs from the ROLO study (Randomised cOntrol trial of LOw glycaemic index diet versus no dietary intervention to prevent recurrence of fetal macrosomia). Food diaries as well as food frequency and lifestyle and physical activity questionnaires were completed during pregnancy. Maternal anthropometry was measured throughout pregnancy and neonatal anthropometry was measured at birth. RESULTS: Multiple linear regression analysis revealed the main maternal factor associated with increased birth weight was greater gestational weight gain R2adj 23.3% (F = 11.547, p < 0.001). The main maternal factor associated with increased birth length was non-smoking status R2adj 27.8% (F = 6.193, p < 0.001). Neonatal central adiposity (determined using waist:length ratio) was negatively associated with maternal age, and positively associated with the following parameters: smoking status, maternal pre-pregnancy arm circumference, percentage energy from saturated fat in late pregnancy, postprandial glucose at 28 weeks gestation and membership of the control group with a positive trend towards association with trimester 2 glycaemic load R2adj 38.1% (F = 8.000, p < 0.001). CONCLUSIONS: Several maternal diet and lifestyle factors were associated with neonatal anthropometry . Low glycaemic index dietary intervention in pregnancy was found to have a beneficial effect on neonatal central adiposity. Additionally, central adiposity was positively associated with maternal dietary fat intake and postprandial glucose highlighting the important role of healthy diet in pregnancy in promoting normal neonatal adiposity. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54392969.

Sexual dimorphism and the placenta - results from the ROLO kids study.

BACKGROUND/AIMS: To assess the association between placental morphology and neonatal and infant anthropometry, including analysis by sex. STUDY DESIGN: Data from the ROLO Kids [Randomized COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analyzed including placental weight and morphology. Placental, anthropometric and skinfold measurements were recorded as markers of adiposity in 196 neonates and 215 infants at 6 months of age. Ratios including subscapular-to-triceps skinfold ratio and waist-to-height ratio were used as markers of central adiposity, while the sum of all skinfolds and subscapular plus triceps skinfolds were used as markers of general adiposity. Analysis was performed for total groups and by sex. RESULTS: On simple linear regression placental weight was associated with neonatal and infant anthropometric measurements. On multiple regression, the placental weight was associated with birth weight. In the neonatal period placental weight was associated with general adiposity in males only (sum of skinfolds (B 0.007, p < .001) and subscapular + triceps skinfolds a marker of general adiposity (B 0.004 p < .001)). At 6 months of age placental length was positively associated with central adiposity in the total group (B 0.006, p .036) and maximum cord diameter was inversely associated with infant central adiposity (B - 0.309 p .043) in males only. CONCLUSION: The placental phenotype is associated with anthropometry at birth and this association persists to early infancy with a stronger relationship noted in this cohort amongst males. This suggests sexual dimorphism may play a role in the impact of the placenta on infant anthropometry.

The association of a low glycaemic index diet in pregnancy with child body composition at 5 years of age: A secondary analysis of the ROLO study.

INTRODUCTION: Childhood obesity remains a significant global health concern. Early intervention through maternal diet during pregnancy represents a possible mode of improving childhood adiposity. AIM: To examine the impact of a low glycaemic index diet during pregnancy on offspring anthropometry at 5 years of age. METHODS: This is a secondary analysis of 387 children from the ROLO pregnancy study 5 years' post-intervention. At the follow-up, BMI, circumferences and skinfold thickness were obtained. A subgroup of 103 children had a DXA scan completed. Statistical analyses included Independent sample t tests, Mann Whitney-U tests and chi-square tests to compare the intervention and control groups. Adjusted analysis using linear regression controlled for significant confounders between participants who returned at follow-up and those that did not. RESULTS: There were no significant differences in BMI (16.05 kg/m2 vs 16.16 kg/m2 , P = 0.403), general adiposity (36.60 mm vs 36.00 mm, P = 0.920), central adiposity (0.61 mm vs 0.60 mm, P = 0.540), total fat mass (4.91 kg vs 4.71 kg, P = 0.377) or total lean mass (14.29 kg vs 14.56 kg, P = 0.386) between the intervention and control groups, respectively. No associations were observed in 5-year outcomes in adjusted analyses when controlling for maternal age at delivery, maternal early pregnancy BMI, maternal education and gestational age. CONCLUSION: Our study found no evidence that a low glycaemic index diet in pregnancy impacts offspring anthropometry 5 years' post-intervention. Therefore, modulating maternal carbohydrate quality in pregnancy may not be an appropriate approach to improving weight status in childhood. Future research should investigate the impact of other dietary practices in pregnancy on child health.

Breastfeeding and maternal eating behaviours are associated with child eating behaviours: findings from the ROLO Kids Study.

BACKGROUND: Child eating behaviours can negatively contribute to the development of childhood obesity. This study investigated associations between breastfeeding habits, maternal eating behaviours and child eating behaviours, in 5-year-old children. METHODS: Secundigravida women were recruited to the ROLO dietary randomised controlled trial (Dublin, Ireland) and were followed up with their children to 5 years of age. Breastfeeding exposure and duration were obtained at postnatal and infant follow-up at 2 and 6 months and 2 and 5 years. At 5 years, maternal and child eating behaviours were measured using the Three Factor Eating Questionnaire and the Child Eating Behaviour Questionnaire, respectively. Regression determined associations between breastfeeding habits and maternal eating behaviours with child eating behaviours, controlling for RCT group, maternal education level, maternal BMI at 5 years, childcare exposure and child BMI centile at 5-year follow-up. RESULTS: There were 230 mother and child pairs analysed. One hundred and fifty-eight mothers had initiated breastfeeding. Median breastfeeding duration was 22 (IQR 33) weeks. Children who were never breastfed were more likely to express a desire to drink (B = -1.01, p = 0.022). Longer breastfeeding duration was associated with lower food responsiveness (B = -1.71, p = 0.003). Maternal uncontrolled eating was positively associated with child food responsiveness, emotional overeating and emotional undereating (B = 0.21, p < 0.001; B = 0.14, p = 0.005; B = 0.14, p = 0.005, respectively). Maternal emotional eating was associated with child emotional overeating and undereating (B = 0.27, p < 0.001, B = 0.29, p = 0.004, respectively). CONCLUSION: Not breastfeeding and short breastfeeding duration may contribute to the development of obesogenic eating behaviours in children, alongside maternal eating behaviours including uncontrolled and emotional eating. These 'food approach' eating behaviours may increase risk of overweight/obesity as they are associated with increased energy intake, hence the importance of research surrounding eating behaviours.

Perinatal inflammation and childhood adiposity - a gender effect?

Background: To determine the association of maternal and fetal inflammatory factors with gender-specific infant adiposity, independent of leptin.Methods: Analysis of anthropometry from 265 mother-infant pairs at birth and 280 pairs at 6 months from the randomised control trial of low glycaemic index diet in pregnancy (ROLO) study (Randomised control trial of low glycaemic index diet) and their association with Maternal TNF-alpha, interleukin 6 and leptin as measured in early and late pregnancy and fetal levels in cord blood.Results: No associations were noted in the male cohort. On multiple regression amongst the female neonatal cohort late pregnancy IL-6 was inversely associated with sum of skinfolds (p ≤ .001); at 6 months infant sum of skinfolds were positively associated with early pregnancy IL-6 (p = .046) and central adiposity positively associated with early pregnancy TNF alpha (p = .018) independent of leptin.Conclusion: Although maternal inflammatory cytokines were not associated with neonatal adiposity independent of leptin (as this association is known), both IL-6 and TNF-α were associated with female infant anthropometry at 6 months of age independent of leptin. These results suggest inflammatory cytokines may exert an in-utero influence on later infant adiposity with a tendency to influence female adiposity more than male. Further research is required to ascertain whether these cytokines may be used as reliable early predictors of infant adiposity.

Associations of maternal and fetal SCD-1 markers with infant anthropometry and maternal diet: Findings from the ROLO study.

BACKGROUND: Elevated stearoyl-CoA desaturase 1 (SCD-1) activity showed associations with obesity in cross-sectional studies. In non-pregnant populations, nutrition regulates SCD-1 transcription and activity. OBJECTIVE: To investigate the longitudinal associations of maternal and fetal SCD-1 activity markers with infant anthropometry up to 2 years of age, and to explore how selected dietary intakes modulate SCD-1 activity in pregnancy. METHODS: As a secondary analysis from the ROLO intervention study, which was conducted in a population at risk for macrosomia, non-esterified fatty acids (NEFA) from maternal plasma at 13 and 28 weeks' gestation and in cord blood were measured via liquid-chromatography-mass-spectrometry. Fatty acid ratios 18:1/18:0 and 16:1/16:0 were used as markers for SCD-1 activity ('desaturation indices', DIs). Relationships of DIs with infant anthropometry up to 2 years of age and maternal dietary parameters during pregnancy were investigated using adjusted linear regression models and p-values correction for multiple testing. RESULTS: 18:1/18:0, but not 16:1/16:0, was associated with measures of infant anthropometry at birth (maternal and fetal markers) and up to 2 years of age (maternal markers only). Dietary intakes did not show strong associations with 18:1/18:0, but 16:1/16:0 was associated with absolute and relative dietary intakes. CONCLUSIONS: In a population at risk for macrosomia, maternal SCD-1 activity measured via 18:1/18:0 was involved in the fetal programming of infant obesity, but could not be substantially modulated by short-term diet in pregnancy. CLINICAL TRIAL REGISTRATION: ISRCTN Registration number: ISRCTN54392969 (http://www.isrctn.com/ISRCTN54392969).

Child Care Exposure Influences Childhood Adiposity at 2 Years: Analysis from the ROLO Study.

BACKGROUND: The first 2 years of life are instrumental for childhood physical development. Factors contributing to childhood obesity are difficult to determine; child care exposure is one to consider, by influencing food preference and physical activity development. OBJECTIVE: To investigate the association of child care exposure with adiposity at 2 years. METHODS: Data were collected as part of the secondary analysis of the prospective ROLO study (randomized control trial of low glycemic index diet) in Dublin, Ireland. Mothers were recruited antenatally and followed up at 2 years postpartum. Maternal and childhood anthropometric data and lifestyle questionnaires, reporting on child care attendance (defined as nonparental care), exposure (weeks), and infant-feeding practices, were collected. RESULTS: Anthropometric measures and lifestyle data were collected for 273 mothers and children aged 2 years, 52.7% of whom attended child care. Child care was predominately provided by a nonrelative (83.7%), either in a crèche (57%) or by a childminder (26.7%). More than half (56.2%) of the children attended child care part-time (≤30 hours/week). Central adiposity measures (abdominal circumference, waist:height ratio) and total adiposity (sum of all skin folds) were significantly elevated in children with increasing time in child care. Children provided with "meals and snacks" had elevated adiposity measures versus those given "snacks or no food." No difference in the infant-feeding practices was identified between the child care groups. CONCLUSIONS: Children attending child care have higher total and central adiposity, proportional to exposure. More research is required to investigate this link to appropriately design health promotion and obesity prevention programs targeting children at 2 years.

An examination of whether associations exist between maternal and neonatal 25OHD and infant size and adiposity at birth, 6-9 months and 2-2.5 years of age - a longitudinal observational study from the ROLO study.

BACKGROUND: Vitamin D status in pregnancy and offspring bone health effects are well established, yet limited knowledge exists on the effect of maternal vitamin D status on offspring size/adiposity. This study examines the association of early (13 weeks), late (28 weeks) pregnancy and neonatal (umbilical) 25-hydroxyvitamin D (25OHD) on offspring size/adiposity. METHODS: This analysis included mother-infant pairs from the ROLO study at birth (n = 292), 6-9 months (n = 160) and 2-2.5 years (n = 287) postpartum. RESULTS: Using Institute of Medicine 2011 Report criteria, 30% of women in early pregnancy and 38% in late pregnancy were at risk of vitamin D deficiency (25OHD < 30 nmol/L). Birthweight was negatively associated with early-pregnancy 25OHD (p = 0.004) and neonatal 25OHD (p < 0.001). Birth length was not associated with 25OHD. Neonatal measures of overall adiposity were negatively associated with neonatal 25OHD (p = 0.001, and p = <0.001 respectively). At 2-2.5 years there was a negative association between weight-for-age z-score and early-pregnancy 25OHD (p < 0.041). CONCLUSIONS: Maternal and neonatal 25OHD were negatively associated with offspring size/adiposity at birth and offspring weight-for-age at 2-2.5 years. Results may not reflect a general population replete in vitamin D, due to high prevalence of macrosomia and high risk of deficiency in this cohort. Improvement of pregnancy vitamin D status remains a public health concern. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54392969. 22/04/2009 retrospectively registered.

Maternal Nutrition and Glycaemic Index during Pregnancy Impacts on Offspring Adiposity at 6 Months of Age--Analysis from the ROLO Randomised Controlled Trial.

Childhood obesity is associated with increased risk of adult obesity and metabolic disease. Diet and lifestyle in pregnancy influence fetal programming; however the influence of specific dietary components, including low glycaemic index (GI), remains complex. We examined the effect of a maternal low GI dietary intervention on offspring adiposity at 6 months and explored the association between diet and lifestyle factors in pregnancy and infant body composition at 6 months. 280 6-month old infant and mother pairs from the control (n = 142) and intervention group (n = 138), who received low GI dietary advice in pregnancy, in the ROLO study were analysed. Questionnaires (food diaries and lifestyle) were completed during pregnancy, followed by maternal lifestyle and infant feeding questionnaires at 6 months postpartum. Maternal anthropometry was measured throughout pregnancy and at 6 months post-delivery, along with infant anthropometry. No difference was found in 6 months infant adiposity between control and intervention groups. Maternal trimester three GI, trimester two saturated fats and trimester one and three sodium intake were positively associated with offspring adiposity, while trimester two and three vitamin C intake was negatively associated. In conclusion associations were observed between maternal dietary intake and GI during pregnancy and offspring adiposity at 6 months of age.

The association between maternal nutrition and lifestyle during pregnancy and 2-year-old offspring adiposity: analysis from the ROLO study.

AIM: To examine the association between maternal nutrition and lifestyle factors and offspring adiposity, using baseline and 2-year postpartum follow-up data from a randomised control trial of low glycaemic index diet. SUBJECT AND METHODS: Food diaries and lifestyle questionnaires were completed during pregnancy and infant feeding and maternal lifestyle questionnaires 2 years postpartum for 281 mother and infant pairs from the ROLO study. Maternal anthropometry was measured throughout pregnancy and infant and maternal anthropometry was measured 2 years postpartum. RESULTS: Maternal 2 year postpartum body mass index (BMI) was positively associated with offspring BMI-for-age z-score (B = 0.105, p = 0.015). Trimester 2 saturated fat intake was positively associated with offspring subscapular:triceps skinfold ratio (B = 0.018, p = 0.001). Trimester 1 glycaemic index was also positively associated with offspring sum of subscapular and triceps skinfolds (B = 0.009, p = 0.029). CONCLUSIONS: Maternal BMI 2 years postpartum was positively associated with offspring BMI. Pregnancy saturated fat intake was positively and polyunsaturated fat negatively associated with offspring adiposity. While further research is necessary, pregnancy and the postpartum period may be early opportunities to combat childhood obesity.

Preservation of Earth-forming events in the tungsten isotopic composition of modern flood basalts.

How much of Earth's compositional variation dates to processes that occurred during planet formation remains an unanswered question. High-precision tungsten isotopic data from rocks from two large igneous provinces, the North Atlantic Igneous Province and the Ontong Java Plateau, reveal preservation to the Phanerozoic of tungsten isotopic heterogeneities in the mantle. These heterogeneities, caused by the decay of hafnium-182 in mantle domains with high hafnium/tungsten ratios, were created during the first ~50 million years of solar system history, indicating that portions of the mantle that formed during Earth's primary accretionary period have survived to the present.