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Background: Vitamin D deficiency in pregnancy is reported as a prevalent public health problem. Objectives: We aimed to evaluate, in pregnant Canadian women, 1) vitamin D intake, 2) maternal and cord serum 25-hydroxycholecalciferol [25(OH)D] and maternal 1,25-dihydroxycholecalciferol [1,25(OH)2D], and 3) factors associated with maternal serum 25(OH)D. Methods: Women (n = 187; mean prepregnancy BMI 24.4 kg/m2, mean age 31 y) recruited to the Be Healthy in Pregnancy study provided fasting blood samples and nutrient intake at 12-17 (early) and 36-38 (late) weeks of gestation, and cord blood. Vitamin D intakes (Nutritionist Pro™) and serum 25(OH)D and 1,25(OH)2D concentrations (LC-tandem MS) were measured. Results: Vitamin D intake was comparable in early and late pregnancy [median (IQR) = 586 (459, 859) compared with 689 (544, 974) IU/d; P = 0.83], with 71% consumed as supplements. Serum 25(OH)D was significantly higher in late pregnancy (mean ± SD: 103.1 ± 29.3 nmol/L) than in early pregnancy (82.5 ± 22.5 nmol/L; P < 0.001) and no vitamin D deficiency (50 nmol/L in healthy Canadian pregnant women. This trial was registered at clinicaltrials.gov as NCT01693510.

Introduction Due to bone fragility, children with acute lymphoblastic leukemia (ALL) have a 6-fold greater fracture risk during therapy compared to peers. Osteoporotic fractures are a concern, as they lead to adverse health outcomes including pain, loss of height due to vertebral deformity, and (transient) disability. In previous studies, lower lumbar spine bone mineral density (LS BMD) at ALL diagnosis was found to be prognostic for the occurrence of future fractures. However, routinely performing dual-energy X-ray absorptiometry (DXA) in each newly diagnosed child is not universally feasible. The aim of this study is to develop and validate an easy to use clinical risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤-2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation. Methods Children treated for ALL according to the Dutch Childhood Oncology Group (DCOG-ALL9; model development) protocol (n=249; median age: 7.6 years [range: 4.0-16.6 years]) and children from the Canadian STeroid-Associated Osteoporosis in the Pediatric Population (STOPP; model validation) cohort (n=99; median age: 7.3 years [range: 4.0-16.6 years]) were included in this study. Multivariable logistic regression analyses were used to develop the prediction model for low LS BMD at diagnosis, defined as a Z-score ≤-2.0 (evaluated with DXA). Candidate predictors included sex, age, height and weight Z-scores at diagnosis of ALL. The receiver operating characteristic area under the curve (AUC) was assessed for model performance. To confirm the association between low LS BMD at diagnosis and bone fragility during and shortly following ALL therapy, we performed multivariable logistic regression analyses. The dependent variables were: one or more symptomatic fractures from ALL diagnosis to 12 months following treatment cessation and low LS BMD at cessation of treatment. In addition, because of homogeneity in the intended glucocorticoid doses, we combined data from the DCOG-ALL9 and STOPP cohorts and performed multivariable pooled cohort analyses (meta-analysis). Potential associations between the six-month cumulative glucocorticoid dose and fractures that occurred in the first year of therapy, were explored. Furthermore, we assessed potential associations between the cumulative glucocorticoid dose at cessation of therapy, and the endpoints 'low LS BMD at therapy cessation' and 'fractures that occurred during treatment and within 12 months following treatment cessation'. Results The prediction model for low LS BMD at diagnosis included weight Z-scores (β = -0.70) and age (β = -0.10) at diagnosis. This model had an AUC of 0.71 (0.63 to 0.78) in the DCOG-ALL9 cohort, and resulted in correct identification of 71% of patients with low LS BMD at ALL diagnosis. Validation on the STOPP cohort showed an AUC of 0.74 (95% CI = 0.63 to 0.84). To calculate the probability of low LS BMD at ALL diagnosis for an individual patient, an online calculator is available at http://lsbmd-risk-calculator.azurewebsites.net/ We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR = 5.9; 95% CI = 3.2 to 10.9) and with symptomatic fractures (OR = 1.7; 95% CI = 1.3 to 2.4) that occurred from diagnosis until 12 months following treatment cessation. In pooled meta-analysis, lower LS BMD at diagnosis (OR = 1.6, 95% CI = 1.1 to 2.4) and six-month cumulative glucocorticoid dose (OR = 1.9, 95% CI = 1.1 to 3.3, for every gram increase) were associated with symptomatic fractures that occurred in the first year of therapy. Higher cumulative glucocorticoid dose at cessation of therapy (OR = 1.5, 95% CI = 1.2 to 2.0, for every gram increase), lower LS BMD Z-scores at diagnosis (OR = 7.9, 95% CI = 4.8 to 13.1) and higher age at diagnosis (OR = 1.6, 95% CI = 1.4 to 1.8), were associated with low LS BMD at cessation of therapy. Conclusion We developed and successfully validated a risk prediction model for low LSBMD at diagnosis in children aged 4-18 years with ALL. This is important because low LS BMD at diagnosis was strongly associated with bone fragility and fractures during and shortly following treatment for ALL. Our easy to use prediction model, can facilitate awareness and early identification of bone fragility in individual pediatric ALL patients, without performing DXA examination. Disclosures No relevant conflicts of interest to declare.

Background Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic status from a biospecimen. Methods In the Family Atherosclerosis Monitoring In earLY life (FAMILY) prospective birth cohort study, we selected 228 cases of MetS and 228 matched controls among children age 5 years. In addition, a continuous MetS risk score was calculated for all 456 participants. Comprehensive metabolite profiling was performed on fasting serum samples using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariable regression models were applied to test metabolite associations with MetS adjusting for covariates of screen time, diet quality, physical activity, night sleep, socioeconomic status, age, and sex. Results Compared to controls, thirteen serum metabolites were identified in MetS cases when using multivariable regression models, and using the quantitative MetS score, an additional eight metabolites were identified. These included metabolites associated with gluconeogenesis (glucose (odds ratio (OR) 1.55 [95% CI 1.25–1.93]) and glutamine/glutamate ratio (OR 0.82 [95% CI 0.67–1.00])) and the alanine-glucose cycle (alanine (OR 1.41 [95% CI 1.16–1.73])), amino acids metabolism (tyrosine (OR 1.33 [95% CI 1.10–1.63]), threonine (OR 1.24 [95% CI 1.02–1.51]), monomethylarginine (OR 1.33 [95% CI 1.09–1.64]) and lysine (OR 1.23 [95% CI 1.01–1.50])), tryptophan metabolism (tryptophan (OR 0.78 [95% CI 0.64–0.95])), and fatty acids metabolism (carnitine (OR 1.24 [95% CI 1.02–1.51])). The quantitative MetS risk score was more powerful than the dichotomous outcome in consistently detecting this metabolite signature. Conclusions A distinct metabolite signature of pediatric MetS is detectable in children as young as 5 years old and may improve risk assessment at early stages of development.

Exposure to sub-optimal maternal vitamin D status during pregnancy has been linked to inadequate in utero bone growth with potential for post-natal deficits, but reported findings are inconsistent. Possible reasons include measurement error in assessing bone length/height, or lack of adjustment for confounding variables such as maternal/infant diet, physical activity and season of birth. The objective of this study was to determine the maternal and child factors associated with bone length traits in children at 3 years of age as part of a longitudinal follow-up of a pregnancy cohort.Mother-child dyads enrolled in the Family Atherosclerosis Monitoring In early Life study were included. Maternal serum 25-hydroxyvitamin D (25(OH)D) concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Anthropometry, physical activity by questionnaire and dietary assessment by food frequency questionnaire were completed for mothers during pregnancy (27-40 weeks gestation) and for children at 3 years with diet by 3-day food records (Nutritionist Pro). Whole body bone mineral density in mother and child (n = 473) was measured by dual-energy absorptiometry (DXA) at the 3 year visit. A software program was developed using MATLAB to derive bone length measurements from whole body DXA images using 8 long bones of each child. Association between maternal and child variables with offspring bone length was assessed using unadjusted and adjusted multivariate linear regression analyses.In the final adjusted multivariate regression model, factors associated with child bone length were maternal height (p = 0.05), child birth length (p = 0.005) and child weight z-score at 3 years (p 0.001). No association was observed between maternal serum 25(OH)D concentrations in pregnancy (of which 77% were in normal range) and child bone length.In healthy Canadian mothers and their children, the factors associated with child bone length achieved at 3 years of age appear to be related to genetic traits rather than environmental exposures. Measures of the length of long bones in children using DXA scans may have provided a more accurate assessment of bone length than whole body height measures.

While the role of vitamin D in supporting bone homeostasis during growth and maintenance is well substantiated, emerging evidence from ecological and observational studies suggests that a deficiency of vitamin D is associated with some cancers, immune disorders, cardiovascular disease, abnormal glucose metabolism, and neurodegenerative diseases. Biological plausibility for extraskeletal functions originated with the discovery of the vitamin D receptor in many body tissues and knowledge that the conversion of 25-hydroxyvitamin D (25(OH)D) to its active metabolite 1,25(OH)2D occurs in many cell types in addition to the kidney. The association of vitamin D status in humans as an etiological factor in developmental programming of bone, in some chronic diseases, and in all-cause mortality, in addition to skeletal morbidity, is supported by some but not all observational studies and randomized controlled trials. These clinical observations have implications for paleopathology, both in terms of specific comorbidities and the potential role of vitamin D in individuals who display no evidence for skeletal disease. This paper outlines recent clinical research on vitamin D metabolism and its novel biological roles, and explores the possible relevance to paleopathological research designs, theoretical models, and interpretations of disease experience.

Background Evidence from epidemiological and animal studies support the concept of programming fetal, neonatal, and adult health in response to in utero exposures such as maternal obesity and lifestyle variables. Excess gestational weight gain (GWG), maternal physical activity, and sub-optimal and excess nutrition during pregnancy may program the offspring’s risk of obesity. Maternal intake of dairy foods rich in high-quality proteins, calcium, and vitamin D may influence later bone health status. Current clinical practice guidelines for managing GWG are not founded on randomized trials and lack specific “active intervention ingredients.” The Be Healthy in Pregnancy (BHIP) study is a randomized controlled trial (RCT) designed to test the effectiveness of a novel structured and monitored Nutrition + Exercise intervention in pregnant women of all pre-pregnancy weight categories (except extreme obesity), delivered through prenatal care in community settings (rather than in hospital settings), on the likelihood of women achieving recommended GWG and a benefit to bone status of offspring and mother at birth and six months postpartum. Methods The BHIP study is a two-site RCT that will recruit up to 242 participants aged > 18 years at 12–17 weeks of gestation. After baseline measures, participants are randomized to either a structured and monitored Nutrition + Exercise (intervention) or usual care (control) program for the duration of their pregnancy. The primary outcome of the study is the percent of women who achieve GWG within the Institute of Medicine (IOM) guidelines. The secondary outcomes include: (1) maternal bone status via blood bone biomarkers during pregnancy; (2) infant bone status in cord blood; (3) mother and infant bone status measured by dual-energy absorptiometry scanning (DXA scan) at six months postpartum; (4) other measures including maternal blood pressure, blood glucose and lipid profiles, % body fat, and postpartum weight retention; and (5) infant weight z-scores and fat mass at six months of age. Discussion If effective, this RCT will generate high-quality evidence to refine the nutrition guidelines during pregnancy to improve the likelihood of women achieving recommended GWG. It will also demonstrate the importance of early nutrition on bone health in the offspring. Trial registration ClinicalTrials.gov, NCT01689961 Registered on 21 September 2012. Electronic supplementary material The online version of this article (10.1186/s13063-018-3065-x) contains supplementary material, which is available to authorized users.

Context Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. Objective This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. Methods Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. Results A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean –0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (–0.6, SD 0.9). Conclusion VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

Objectives Gestational weight gain (GWG) is increasingly monitored in the United States and Canada. While promoting healthy GWG offers benefits, there may be costs with over-surveillance. We aimed to explore these costs/benefits. Methods Quantitative data from 350 pregnant survey respondents and qualitative focus group data from 43 pregnant/post-partum and care-provider participants were collected in the Mothers to Babies (M2B) study in Hamilton, Canada. We report descriptive statistics and discussion themes on GWG trajectories, advice, knowledge, perceptions, and pregnancy diet. Relationships between GWG monitoring/normalization and worry, knowledge, diet quality, and sociodemographics-namely low-income and racialization-were assessed using χ2 tests and a linear regression model and contextualized with focus group data. Results Most survey respondents reported GWG outside recommended ranges but rejected the mid-20th century cultural norm of "eating for two"; many worried about gaining excessively. Conversely, respondents living in very low-income households were more likely to be gaining less than recommended GWG and to worry about gaining too little. A majority had received advice about GWG, yet half were unable to identify the range recommended for their prepregnancy BMI. This proportion was even lower for racialized respondents. Pregnancy diet quality was associated with household income, but not with receipt or understanding of GWG guidance. Care-providers encouraged normalized GWG, while worrying about the consequences of pathologizing "abnormal" GWG. Conclusions Translation of GWG recommendations should be done with a critical understanding of GWG biological normalcy. Supportive GWG monitoring and counseling should consider clinical, socioeconomic, and community contexts.

Background Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability. Objectives To identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic cohort of pregnant women. Design In this cross-sectional analysis of 3 multiethnic Canadian birth cohorts, we collected semiquantitative FFQ and serum data from 900 women at the second trimester of pregnancy. We calculated a diet quality score (DQS), defined as daily servings of “healthy” minus “unhealthy” foods. Serum metabolomics was performed by multisegment injection-capillary electrophoresis-mass spectrometry, and specific serum metabolites associated with maternal DQSs were identified. We combined the results across all 3 cohorts using meta-analysis to classify robust dietary biomarkers (r > ± 0.1; P 75%) and adequate precision (CV, Study identifies robust dietary biomarkers of dietary patterns and foods in pregnant women.

Background: Sparse data exists on the utility of individual serum non-esterified fatty acids (NEFAs) as clinical and dietary biomarkers and how reporting methods could affect these associations. We investigated the associations of 19 serum NEFAs expressed as µM or mol%, with self-reported dietary intake data, and cardiometabolic health indicators in pregnant women. Methods: In this cross-sectional study, 273 pregnant women in their second trimester each completed a semi-quantitative food-frequency questionnaire and provided fasting serum samples. Comprehensive serum NEFA analysis was performed by multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry. We evaluated the associations of NEFAs using two different reporting methods, with diet quality, specific foods intake, and measures of adiposity and glucose homeostasis. Results: Consistently stronger dietary correlations were observed when expressed as mol%. Serum ω-3 NEFAs were associated with diet quality and fish/fish oil daily servings (DHA mol%, r=0.37; p=4.8e-10), and odd-chain NEFAs were associated with full-fat dairy intake (15:0 mol%, r=0.23; p=9.0e-5). Glucose intolerance was positively associated with odd chain NEFAs as expressed in µM (r=0.21; p=0.001) but inversely associated when expressed as mol% (r=-0.31; p=2.2e-7). In contrast, monounsaturated NEFAs (µM and mol%) had robust positive associations with pre-pregnancy BMI, second trimester skin-fold thickness, glycated hemoglobin, fasting glucose, and glucose intolerance. Conclusions: This study demonstrates the utility of specific NEFAs and their sub-classes as viable dietary and clinical biomarkers when reported as their relative proportions. More research is needed to investigate inconsistencies between absolute concentrations and relative proportions when reporting fatty acids.

Environmental factors affecting development through embryogenesis, pregnancy, and infancy impact health through all subsequent stages of life. Known as the Developmental Origins of Health and Disease (DOHaD) hypothesis, this concept is widely accepted among health and social scientists. However, it is unclear whether DOHaD-based ideas are reaching the general public and/or influencing behaviour. This study thus investigated whether and under what circumstances pregnant people in Canada are familiar with DOHaD, and if DOHaD familiarity relates to eating behaviour. Survey responses from pregnant people from Hamilton, Canada, were used to assess respondents' knowledge of DOHaD (hereafter, DOHaDKNOWLEDGE) compared with their knowledge of more general pregnancy health recommendations (Pregnancy GuidelineKNOWLEDGE). The survey also characterized respondents' pregnancy diet quality and sociodemographic profiles. We fit two multiple, linear, mixed regression models to the data, one with DOHaDKNOWLEDGE score as the dependent variable and the other with diet quality score as the dependent. In both models, responses were clustered by respondents' neighbourhoods. Complete, internally consistent responses were available for 330 study-eligible respondents. Relative to Pregnancy GuidelineKNOWLEDGE, respondents had lower, more variable DOHaDKNOWLEDGE scores. Additionally, higher DOHaDKNOWLEDGE was associated with higher socio-economic position, older age, and lower parity, independent of Pregnancy GuidelineKNOWLEDGE. Diet quality during pregnancy was positively associated with DOHaDKNOWLEDGE, adjusting for sociodemographic factors. A subset of relatively high socio-economic position respondents was familiar with DOHaD. Greater familiarity with DOHaD was associated with better pregnancy diet quality, hinting that translating DOHaD knowledge to pregnant people may motivate improved pregnancy nutrition and thus later-life health for developing babies.

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation. The increasing proportions of elderly citizens, the growing prevalence of chronic diseases, and the persistently high prevalence of overweight and obesity, which predispose to chronic disease, highlight the importance of understanding the impact of nutrition on chronic disease prevention and control. A multidisciplinary working group sponsored by the Canadian and US government DRI steering committees met from November 2014 to April 2016 to identify options for addressing key scientific challenges encountered in the use of chronic disease endpoints to establish reference values. The working group focused on 3 key questions: 1) What are the important evidentiary challenges for selecting and using chronic disease endpoints in future DRI reviews, 2) what intake-response models can future DRI committees consider when using chronic disease endpoints, and 3) what are the arguments for and against continuing to include chronic disease endpoints in future DRI reviews? This report outlines the range of options identified by the working group for answering these key questions, as well as the strengths and weaknesses of each option.

BACKGROUND The genetic influence on child obesity has not been fully elucidated. OBJECTIVE This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old. METHODS A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. RESULTS The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10-3 and 5.08 × 10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10-6 and 3.75 × 10-5 , respectively). CONCLUSIONS SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.

Excess gestational weight gain is associated with short‐ and long‐term pregnancy complications. Although a healthy diet and physical activity during pregnancy are recommended and shown to reduce the risk of complications and improve outcomes, adherence to these recommendations is low. The aims of this study were to explore women's view of nutrition and physical activity during pregnancy and to describe barriers and facilitators experienced in implementing physical activity and nutrition recommendations. In a substudy of the Be Healthy in Pregnancy randomized trial, 20 semistructured focus groups were conducted with 66 women randomized to the control group when they were between 16 and 24 weeks gestation. Focus groups were recorded, transcribed verbatim, coded and thematically analysed. The results indicate that women felt motivated to be healthy for their baby, but competing priorities may take precedence. Participants described limited knowledge and access to information on safe physical activity in pregnancy and lacked the skills needed to operationalize both physical activity and dietary recommendations. Women's behaviours regarding diet and physical activity in pregnancy were highly influenced by their own and their peers' beliefs and values regarding how weight gain impacted their health during pregnancy. Pregnancy symptoms beyond women's control such as fatigue and nausea made physical activity and healthy eating more challenging. Counselling from care providers about nutrition and physical activity was perceived as minimal and ineffective. Future interventions should address improving counselling strategies and address individual's beliefs around nutrition and activity in pregnancy.

Purpose: Prenatal multivitamins are recommended in pregnancy. This study assessed food and supplement intakes of folate, vitamin B12 (B12), vitamin D, and choline in pregnant women living in Southern Ontario in comparison with current recommendations.Methods: Women recruited to the Be Healthy in Pregnancy RCT (NCT01693510) completed 3-day diet/supplement records at 12–17 weeks gestation. Intakes of folate, B12, vitamin D, and choline were quantified and compared with recommendations for pregnant women.Results: Folate intake (median (min, max)) was 1963 μg/day dietary folate equivalents (153, 10 846); 90% of women met the Estimated Average Requirement (EAR) but 77% exceeded the Tolerable Upper Intake Level (UL) (n = 232). B12 intake was 12.1 μg/day (0.3, 2336); 96% of women met the EAR with 7% exceeding the EAR 100-fold (n = 232). Vitamin D intake was 564 IU/day (0.0, 11 062); 83% met the EAR, whereas 1.7% exceeded the UL (n = 232). Choline intake was 338 mg/day (120, 1016); only 18% met the Adequate Intake and none exceeded the UL (n = 158).Conclusion: To meet the nutrient requirements of pregnancy many women rely on prenatal vitamins. Reformulating prenatal multivitamin supplements to provide doses of vitamins within recommendations to complement a balanced healthy diet would ensure appropriate micronutrient intakes for pregnant women.

Objective The effects of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) on maternal and offspring obesity traits, as well as the maternal and offspring genetic contribution to GWG and postpartum weight retention, were examined. Methods Blood samples from mothers (n = 608) and offspring (n = 541) were genotyped for 83 BMI-associated SNPs and 47 waist-to-hip ratio (WHR)-associated SNPs. Linear regression and mixed-effects regression models were performed to examine clinical epidemiological and genetic associations with unweighted and weighted BMI and WHR genetic risk scores (GRS). Results Prepregnancy BMI was positively associated with offspring weight and BMI Z-score from birth to 5 years. GWG was positively associated with maternal postpartum weight retention at 1 and 5 years and with offspring weight Z-score from birth to 5 years old. The maternal unweighted BMI GRS was associated with prepregnancy BMI, postpartum weight retention at 5 years, and offspring weight Z-score from birth to 5 years old, but not associated with GWG. Both maternal and offspring unweighted WHR GRSs were negatively associated with GWG. Conclusions Maternal BMI-associated SNPs may contribute to the genetic link between prepregnancy BMI variation, long-term postpartum weight retention, and offspring birth weight and longitudinal weight. Maternal and offspring WHR-associated SNPs may contribute to GWG variation.

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow’s milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45–2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42–0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51–0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50−125 nmol/L, requiring 600–4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50–125 nmol/L (600–4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Background Dietary inadequacy and adiposity, both prevalent in the chronic spinal cord injury (SCI) population, are known to influence bone turnover and may be potential modifiable risk factors for the development of sublesional osteoporosis following SCI. This pilot study in an SCI cohort aimed to assess measures of nutrition and obesity, to determine if these measures were associated with bone mineral density (BMD), and to compare these measures to a non-SCI control cohort. Methods In a cross-sectional observational study, volunteers with chronic SCI (> 1 year post-injury, lesions from C1 to T12 and severity category A–D by the American Spinal Injury Association Impairment Scale) were assessed, and 8 non-SCI individuals were recruited as a comparison group. BMD at the femoral neck (FN) and lumbar spine (LS), and an estimate of visceral adipose tissue (VAT) from lumbar vertebrae 1 through 4 were measured using dual energy X-ray absorptiometry (DXA); nutrient intake of calcium, vitamins D & K, and protein were estimated using a food frequency questionnaire; plasma 25-hydroxyvitamin D (25(OH)D) was analyzed using ultra-high performance liquid chromatography/tandem mass spectroscopy; and serum leptin, adiponectin and insulin were analyzed using a multiplex assay. Results A total of 34 individuals with SCI (n = 22 tetraplegic; n = 12 paraplegic; 94% male) who averaged 12.7 (9.0) years post-injury, age 40.0 (10.9) years and % body fat of 28.4 (7.3) were assessed. Multiple linear regression analyses in the SCI cohort showed significant associations between BMD at the FN and LS with leptin (FN: r = 0.529, p = 0.005; LS: r = 0.392, p = 0.05), insulin (FN: r = 0.544, p = 0.003; LS: r = 0.388, p = 0.05), and VAT percent (FN: r = 0.444, p = 0.02; LS: r = 0.381, p = 0.05). Adiponectin was only correlated with LS BMD (r = 0.429, p = 0.03). No significant relationships were found between BMD and serum 25(OH)D, or intakes of calcium, vitamins D & K, and protein. Intake of vitamin D was adequate in 69% of participants with SCI, where 91% of those persons consumed either vitamin D and/or multivitamin supplements. Vitamin D status was similar between SCI and non-SCI groups as was sub-optimal status (25(OH)D, Highlights • In SCI subjects, BMD was positively associated with adiposity. • Adipokine regulation may be more important for bone status in chronic SCI. • Compromised BMD in SCI was not attributed to suboptimal vitamin D or bone nutrients. • Widespread variability in SCI stage/severity may have influenced lack of association. • Suboptimal 25(OH)D status was seen in 60% of an SCI cohort, despite vitamin D supplement use in 63%.

Objectives. To determine (1) whether intramuscular adipose tissue (IntraMAT) differs between women with and without type 2 diabetes and (2) the association between IntraMAT and mobility and strength.Methods. 59 women ≥ 65 years with and without type 2 diabetes were included. A 1-Tesla MRI was used to acquire images of the leg. Timed-up-and-go (TUG) and grip strength were measured. Regression was used to determine associations between the following: (1) type 2 diabetes and IntraMAT (covariates: age, ethnicity, BMI, waist : hip ratio, and energy expenditure), (2) IntraMAT and TUG (covariates: diabetes, age, BMI, and energy expenditure), and (3) IntraMAT and grip strength (covariates: diabetes, age, height, and lean mass).Results. Women with diabetes had more IntraMAT. After adjustment, IntraMAT was similar between groups (diabetes mean [SD] = 13.2 [1.4]%, controls 11.8 [1.3]%,P=0.515). IntraMAT was related to TUG and grip strength, but the relationships became nonsignificant after adjustment for covariates (difference/percent IntraMAT [95% CI]: TUG = 0.041 seconds [−0.079–0.161],P=0.498, grip strength = −0.144 kg [−0.335–0.066],P=0.175).Conclusions. IntraMAT alone may not be a clinically important predictor of functional mobility and strength; however, whether losses in functional mobility and strength are promoted by IntraMAT accumulation should be explored.

ObjectiveBirth weight is an indicator of newborn health and a strong predictor of health outcomes in later life. Significant variation in diet during pregnancy between ethnic groups in high-income countries provides an ideal opportunity to investigate the influence of maternal diet on birth weight.SettingFour multiethnic birth cohorts based in Canada (the NutriGen Alliance).Participants3997 full-term mother–infant pairs of diverse ethnic groups who had principal component analysis-derived diet pattern scores—plant-based, Western and health-conscious—and birth weight data.ResultsNo associations were identified between the Western and health-conscious diet patterns and birth weight; however, the plant-based dietary pattern was inversely associated with birth weight (β=−67.6 g per 1-unit increase; PConclusionsMaternal consumption of a plant-based diet during pregnancy is associated with birth weight. Among white Europeans, a plant-based diet is associated with lower birth weight, reduced odds of an infant born LGA and increased odds of SGA, whereas among South Asians living in Canada, a plant-based diet is associated with increased birth weight.

Taking the innovative step of considering individuals of all age groups and disease states via aspects of a life course perspective, this study aims to shed light on biocultural factors contributing to vitamin D deficiency in the Roman period assemblage from Isola Sacra, Italy (1st–3rd century AD) comprising 678 individuals (307 nonadults, 371 adults). Active and healed deficiency were identified in nonadults (

BackgroundChildhood obesity is a world-wide concern due to its growing prevalence and association with cardiometabolic risk factors in childhood and subsequent adult cardiovascular disease. In young pre-school children, there is uncertainty regarding which of the commonly used anthropometric measures of childhood obesity is best associated with cardiometabolic risk factors. This study compared the utility of common measures used in identifying obesity in these young children.MethodsThe four commonly used metrics for identifying obesity in children: body fat percentage ≥ 90th percentile, waist circumference ≥ 90th percentile, BMI z score > 2 SD and waist-to-height ratio (WHtR) ≥ 0.5, were measured in a cohort of children born singleton, at full term and followed from birth (n = 761) to 5 years of age (n = 513). The utility of each in identifying cardiometabolic risk factors (fasting lipid profile, fasting blood glucose and blood pressure) was examined.ResultsAt age 5 years, children with percent body fat ≥ 90th percentile or waist circumference ≥ 90th percentile, were associated with higher levels of triglycerides, glucose, and systolic and diastolic blood pressures than those < 90th percentile, respectively. Such differences were not obvious at age 3 years or at birth. A BMI z-score > 2 SD was associated with higher levels of triglycerides and systolic and diastolic blood pressure but not glucose at age 5 years. Differences in HDL cholesterol, fasting glucose and systolic blood pressure were observed in children with BMI z score > 2 SD at age 3 years but not with the other indices of obesity. As almost all children had WHtR ≥ 0.5 at birth, ages 1 and 3 years, this measure could not differentiate increased cardiometabolic risk. At age 5 years, the differences were much more obvious, with significant differences in triglycerides and systolic and diastolic blood pressures between those with WHtR ≥ 0.5 and those with < 0.5.ConclusionEach of the four commonly used measures of childhood obesity shows moderate associations with cardiometabolic risk factors at 5 years, with no advantage of one measure over the other. These associations were less consistent at 3 years of age or younger. These observations have not been reported previously.

OBJECTIVES: Maternal bone health can be compromised in pregnancy if diet and exercise are inadequate. Our objective was to determine the changes of calciotropic hormones and bone biomarkers in response to a maternal high-dairy diet plus exercise intervention compared to usual care from early to late pregnancy. METHODS: As part of the Be Healthy in Pregnancy RCT (Southern Ontario, Canada) (NCT01689961), healthy pregnant women (≤ 17 wk gestation) were randomized to the control or treatment group (Nutrition: 25% protein energy with ∼50% from dairy and Exercise plan: 10,000 daily steps) for the duration of pregnancy. Calcium and vitamin D intakes were analyzed from 3-day diet and supplement records (Nutritionist Pro). Fasted serum was analyzed for 25(OH)D(2) and D(3) and 1,25(OH)(2)D by LC-MS/MS (Waters Corp.); procollagen type I N-terminal propeptide (PINP, Cloud Clone Corp., TX, USA) and insulin growth factor-1 (IGF-1, R&D Systems, MN, USA) by ELISA) at 12–17 and 36–38 wk gestation. T-tests were used to compare groups at baseline. Two-way ANOVA were performed to assess time and treatment effect. RESULTS: In 118 women (86% of European descent, mean (range) pre-pregnancy BMI 24.9 kg/m2 (17.9 – 39.6 kg/m2)), baseline median (Q1, Q3) vitamin D and calcium intakes (585 IU/d (453, 823) and 1192 mg/d (979, 1512)) and bone biomarkers were similar between control and treatment groups. Baseline 25(OH)D was 79.6 nmol/L (66.1, 97.7), 1,25(OH)(2)D was 71.5 pmol/L (62.3, 89.8), PINP was 57.0 ng/mL (37.4, 74.2) and IGF-1 was 178.0 ng/mL (132.0, 212.0). At the end of pregnancy, concentrations of 25(OH)D, 1,25(OH)(2)D and IGF-1 increased significantly (P

Vitamin D deficiency in pregnancy is widely reported, but whether this applies in North America is unclear since no population-based surveys of vitamin D status in pregnancy exist in Canada or the United States. The objectives were to assess (i) the intake and sources of vitamin D, (ii) vitamin D status, and (iii) factors associated with serum 25-hydroxyvitamin D (25-OHD) concentration in two cohorts of pregnant women from Southern Ontario, Canada, studied over a span of 14 years. Maternal characteristics, physical measurements, fasting blood samples and nutrient intake were obtained at enrolment in 332 pregnant women from the Family Atherosclerosis Monitoring In early Life (FAMILY) study and 191 from the Be Healthy in Pregnancy (BHIP) study. Serum 25-OHD was measured by LC/MS-MS. The median (Q1, Q3) total vitamin D intake was 383 IU/day (327, 551) in the FAMILY study and 554 IU/day (437, 796) in the BHIP study. Supplemental vitamin D represented 64% of total intake in participants in FAMILY and 78% in BHIP. The mean (SD) serum 25-OHD was 76.5 (32.9) nmol/L in FAMILY and 79.7 (22.3) nmol/L in BHIP. Being of European descent and blood sampling in the summer season were significantly associated with a higher maternal serum 25-OHD concentration. In summary, health care practitioners should be aware that vitamin D status is sufficient in the majority of pregnant Canadian women of European ancestry, likely due to sun exposure.

Purpose: The aim was to validate a food frequency questionnaire (FFQ) against a 3-day food record (3DFR) for pregnant women with a focus on nutrients important for bone health from food and supplements. Methods: The FFQ and 3DFR were administered to pregnant women (n = 42) aged 18–45 years in their third trimester of pregnancy in Hamilton, Ontario. Nutrient analysis of intakes was conducted using an FFQ calculator and Nutritionist-Pro software. The average daily serving consumption of Milk and alternatives group and Vegetable subgroup from Canada’s Food Guide were also compared. Results: There was a high positive correlation between methods for total dietary vitamin D (r = 0.83). Low positive associations were observed for total protein (r = 0.37), calcium (r = 0.36), vitamin K (r = 0.41), and servings of Milk and alternatives (r = 0.36). A cross-classification analysis using participants’ intake quartiles revealed no major misclassifications. Bland–Altman analysis showed that the FFQ mildly underestimated the intake for protein, whereas it grossly overestimated the intake of vitamin K, and daily servings of Milk and alternatives and Vegetable. Conclusions: This FFQ can serve as a useful tool in clinical and research settings to assess key bone nutrients from foods and supplement sources in pregnant women.

BACKGROUND:Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood. OBJECTIVES:We investigate whether common genetic variants identified in adults have an effect on glucose in early life. METHODS:610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied. Quantitative trait disequilibrium tests and mixed-effects regressions were conducted to estimate an effect of the SNPs on glucose. RESULTS:Risk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10-3 ≤ P ≤ 4.60x10-2). Together, these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype score (P = 6.33x10-5). None of the associations described in the present study have been reported previously in early childhood. CONCLUSION:Our data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life.

Maternal nutrition plays a crucial role in influencing fertility, fetal development, birth outcomes, and breast milk composition. During the critical window of time from conception through the initiation of complementary feeding, the nutrition of the mother is the nutrition of the offspring—and a mother’s dietary choices can affect both the early health status and lifelong disease risk of the offspring. Most health expert recommendations and government-sponsored dietary guidelines agree that a healthy diet for children and adults (including those who are pregnant and/or lactating) should include an abundance of nutrient-rich foods such as fruits and vegetables. These foods should contain a variety of essential nutrients as well as other compounds that are associated with lower disease risk such as fiber and bioactives. However, the number and amounts of nutrients varies considerably among fruits and vegetables, and not all fruit and vegetable options are considered “nutrient-rich”. Avocados are unique among fruits and vegetables in that, by weight, they contain much higher amounts of the key nutrients folate and potassium, which are normally under-consumed in maternal diets. Avocados also contain higher amounts of several non-essential compounds, such as fiber, monounsaturated fats, and lipid-soluble antioxidants, which have all been linked to improvements in maternal health, birth outcomes and/or breast milk quality. The objective of this report is to review the evidence that avocados may be a unique nutrition source for pregnant and lactating women and, thus, should be considered for inclusion in future dietary recommendations for expecting and new mothers.

Purpose Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. Patient and Methods We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. Results Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006). Conclusion Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.

Background.Osteoporosis is a chronic disease that can significantly impact numerous aspects of health and wellness. The individual consequences of osteoporosis can be devastating, often resulting in substantial loss of independence and sometimes death. One of the few illnesses with greater disease burden than low bone mineral density (BMD) is major depressive disorder (MDD). Both depression and antidepressant use have been identified as secondary causes of osteoporosis. The objective of this paper is to review and summarize the current findings on the relationship between antidepressant use and BMD.Methods.Relevant sources were identified from the Pubmed and MEDLINE databases, citing articles from the first relevant publication to September 1st, 2010.Results.2001 articles initially met the search criteria, and 35 studies were thoroughly reviewed for evidence of an association between SSRI use and BMD, and 8 clinical studies were detailed and summarized in this paper.Conclusions.Current findings suggest a link between mental illness and osteoporosis that is of clinical relevance. Additional longitudinal studies and further research on possible mechanisms surrounding the association between SSRI use on bone metabolism need to be conducted. Treatment algorithms need to recognize this association to ensure that vulnerable populations are screened.

Consolidation and maintenance of peak bone mass in young adulthood may be compromised by inactivity, low dietary calcium, and diet-induced weight loss.We aimed to determine whether higher intakes of dairy foods, dietary calcium, and protein during diet- and exercise-induced weight loss affected markers of bone health.Participants included premenopausal overweight and obese women.Ninety participants were randomized into three groups (n = 30 per group): high protein and high dairy (HPHD), adequate protein and medium dairy (APMD), and adequate protein and low dairy (APLD), differing in dietary protein (30, 15, or 15% of energy, respectively), dairy foods (15, 7.5, or2% of energy from protein, respectively), and dietary calcium (∼1600, ∼1000, or500 mg/d, respectively).Serum and urine bone turnover biomarkers, serum osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), PTH, 25-hydroxyvitamin D, leptin, and adiponectin measured at 0 and 16 wk.All groups lost equivalent body weight (P0.05). N-telopeptide, C-telopeptide (CTX), urinary deoxypyridinoline, and osteocalcin increased in APLD (P0.01), whereas in HPHD, osteocalcin and procollagen 1 amino-terminal propeptide (P1NP) increased (P0.05), and all resorption markers remained unchanged. P1NP to CTX and OPG to RANKL ratios increased in HPHD (P0.005), and P1NP to CTX ratio decreased in APLD (P0.05). PTH decreased in HPHD and APMD vs. APLD (P0.005), and 25-hydroxyvitamin D increased in HPHD (P0.05), remained unchanged in APMD, and decreased in APLD (P0.05). Leptin decreased and adiponectin increased in APMD and HPHD only (P0.001).Hypoenergetic diets higher in dairy foods, dietary calcium, and protein with daily exercise, favorably affected important bone health biomarkers vs. diets with less of these bone-supporting nutrients.

Objective Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM. Methods An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 μm3 voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x-ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up-and-go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI). Results Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups. Conclusion In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population.

Weight loss can have substantial health benefits for overweight or obese persons; however, the ratio of fat:lean tissue loss may be more important. We aimed to determine how daily exercise (resistance and/or aerobic) and a hypoenergetic diet varying in protein and calcium content from dairy foods would affect the composition of weight lost in otherwise healthy, premenopausal, overweight, and obese women. Ninety participants were randomized to 3 groups (n = 30/group): high protein, high dairy (HPHD), adequate protein, medium dairy (APMD), and adequate protein, low dairy (APLD) differing in the quantity of total dietary protein and dairy food-source protein consumed: 30 and 15%, 15 and 7.5%, or 15 and

Background Complex interactions among genetic, epigenetic, and environmental exposures, further modified by a child's postnatal environment, underlie the relationship among maternal health, fetal growth, and the development of cardiovascular disease (CVD) risk factors in the child and disease in the adult. Few available studies consider the genetic and environmental influences of the family, beyond maternal health. The purpose of this study is to examine the fetal and early childhood family-based determinants for the development of adiposity, CVD risk factors, and atherosclerosis in childhood. Method A cohort of 850 children and their families (mother, father, eldest sibling) are being recruited during pregnancy to a prospective longitudinal study to investigate the relative contribution of ( a ) prenatal and postnatal determinants and ( b ) individual and family (maternal/paternal) determinants for the development of adiposity and CVD risk factors at 3, 5, and 10 years of age and carotid intima media thickness at 10 years. Implications The FAMILY study will advance understanding of the fetal and early childhood determinants for CVD development and will contribute to the design of primary prevention programs based on identification of the most important modifiable determinants for early childhood adiposity and CVD risk factor development.

CONTEXT: Obesity is a major public health problem in North America, particularly in Aboriginal people. OBJECTIVE: To determine if a household-based lifestyle intervention is effective at reducing energy intake and increasing physical activity among Aboriginal families after 6 months. DESIGN, PARTICIPANTS, AND INTERVENTION: Randomized, open trial of 57 Aboriginal households recruited between May 2004 and April 2005 from the Six Nations Reserve in Ohsweken, Canada. Aboriginal Health Counsellors made regular home visits to assist families in setting dietary and physical activity goals. Additional interventions included provision of filtered water, a physical activity program for children, and educational events about healthy lifestyles. RESULTS: 57 households involving 174 individuals were randomized to intervention or usual care. Intervention households decreased consumption of fats, oils and sweets compared to usual care households (-4.9 servings per day vs. -3 servings/day, p=0.006), and this was associated with a reduction in trans fatty acids (-0.2 vs. +0.6 grams/day, p=0.02). Water consumption increased (+0.3 vs. -0.1 servings/day, p

The relationship between bone mineral mass and cumulative dose of corticosteroids (CDC) was investigated in 42 children and adolescents treated for Hodgkin disease (HD; n = 22) and non-Hodgkin lymphoma (NHL; n = 20). The median age at the time of the study was 24.1 years for HD survivors and 14.1 years for NHL survivors. Dual-energy X-ray absorptiometry [bone mineral density of the lumbar spine (LS-BMD) expressed as Z-scores] and peripheral quantitative computed tomography at the distal radius [trabecular volumetric BMD (vBMD-trab)] were undertaken. Osteopenia (Z-score-1.00) was found in 9/22 patients with HD and 10/20 with NHL, while 34% (HD = 6, NHL = 8) had a vBMD-trab below the normal range. The CDC correlated inversely with LS-BMD Z-score (r =-0.41, P = 0.007). There was a statistically significantly higher vBMD-trab in patients who received low (1-4 g/m(2)) compared with high (or=20 g/m(2)) CDC (P = 0.031). Treatment of malignant lymphoma with high CDC is a risk factor for development of osteopenia.

The derivation of reference values in 11 current dietary reference standards is often based on methods of extrapolation or interpolation, but these are not consistent across reports. Such methods are frequently employed to derive nutrient intake values (NIVs) for infants and children owing to the paucity of relevant research data available. The most common method is to extrapolate values for children down from those of adults, employing a weight or metabolic factor and adjusting for growth. In some instances, values for young children are extrapolated up from infants, values for adults are extrapolated up from children, or values for older adults are extrapolated up from young adults. Extrapolation is employed to estimate not only nutrient requirement or adequate intake but also the upper tolerable levels of intake. Extrapolation methods may also form the basis of estimates of tissue deposition of nutrients during growth in children and for the maternal/fetal dyad in pregnancy with adjustments for metabolic efficiency. Likewise, recommended intakes during lactation are extrapolated from known secretion of the nutrient in milk with adjustments for bioavailability. For future dietary standards, a first priority is to obtain relevant scientific data using current methodology, such as stable isotope tracers, body composition analysis, and appropriate biomarkers, from which NIVs for each age group can be derived. Extrapolation to derive an NIV is only acceptable in the sheer absence of sound scientific data and must be modeled with a consistent approach. For the purpose of harmonization of dietary standards, we recommend the following approaches that should be clearly described in reports: standardization of age groups on a biological basis (growth and pubertal stages) with consideration of relevant developmental milestones throughout childhood; application of internationally accepted standards for growth, body size, body composition, fetal and maternal nutrient accretion in pregnancy, and milk composition; and inclusion of appropriate adjustments (metabolic efficiency, weight change, or physical activity).

Early detection of abnormalities in bone turnover may be facilitated by assessing biomarkers of bone metabolism including vitamin D status. In many children with cancer, biomarkers of bone formation (osteocalcin, bone specific alkaline phosphatase and carboxy-(or N terminal) propeptide of type 1 procollagen) were observed to be suppressed, while bone resorption was elevated as measured by serum cross-linked (or C-terminal) telopeptide of type 1 collagen. Insulin-like growth factor 1, which stimulates bone formation, may be suppressed indirectly indicating a growth hormone insufficiency. Leptin may also play a role in bone remodeling as hyperleptinemia has been observed in association with acute lymphoblastic leukemia. Evaluation of bone status using such biomarkers is complicated by the lack of universally accepted reference values and the variation by age, gender, or pubertal status. Etiologic factors contributing to the observed skeletal morbidities include disease process, chemotherapy (drugs such as glucocorticoids and methotrexate) and radiotherapy. Other factors common to children with cancer, such as chronic inflammation, dietary changes and physical inactivity, must also be taken into account. The current evidence for abnormalities in biomarkers of vitamin D status and bone turnover will be the focus of this review of published studies.

Intestinal magnesium (Mg) absorption was measured in six healthy children (control) and in four children treated for acute lymphoblastic leukemia with the single-isotope fecal recovery technique (SIFRT). The objective of this study was to determine Mg absorption in young children with acute lymphoblastic leukemia using stable isotope tracers. Fractional and absolute absorption levels determined by SIFRT were not significantly different between children with acute lymphoblastic leukemia (fractional absorption: 58.3 +/- 10.6% [mean +/- SEM], absolute absorption: 3.66 +/- 0.71 mg x kg(-1) x d(-1), [0.15 +/- 0.03 mmol x kg(-1) x d(-1)]) and control children (fractional absorption: 61.4 +/- 7.5%, absolute absorption: 5.69 +/- 0.85 mg x kg(-1) x d(-1), [0.23 +/- 0.03 mmol x kg(-1) x d(-1)]). Average Mg absorption in young children (aged 3--8 y) was 60.2 +/- 5.8%. This study describes the first application of the SIFRT to assess Mg absorption in young children and illustrates the feasibility of the SIFRT in this age group to obtain more accurate information on Mg absorption.

Extremely low birth weight infants who develop severe respiratory disease may have special nutrient requirements imposed by a combination of enhanced utilization of nutrients or the need for epithelial cell repair resulting from the disease process, as well as to support catch-up growth. Inositol, free fatty acids, vitamin E and vitamin A are proposed as nutrients for which infants at risk of chronic pulmonary insufficiency may have special requirements. Of these nutrients, only for vitamin A does suggestive evidence exist that high doses when given intramuscularly may reduce the incidence of death or chronic lung disease. Exogenous steroid therapy (dexamethasone), which is often used to improve pulmonary compliance in ventilated premature infants, may compromise vitamin A status and induce restricted somatic and bone mineral growth. Supplemental nutrition by means of enriched infant formulas has provided benefits in growth and bone mass accretion to infants recovering from bronchopulmonary dysplasia up to 3-mo corrected age. This growth advantage was not sustained over the subsequent 9 mo, suggesting that prolonged nutritional support is required until catch-up growth is complete. Further studies are required to delineate the needs for specific nutrients such as antioxidant vitamins and minerals or vitamin A that may play a role in preventing severe chronic lung disease in premature infants. As well, the role of supplemental nutrition (beyond the requirements of term infants) to support catch-up growth and maintenance during the critical stages of early development requires further investigation before evidence-based nutrient recommendations can be developed for this special population of infants.

The workshop entitled "Early Risk Determinants and Later Health Outcomes: Implications for Research Prioritization and the Food Supply," reported in this issue, was borne of a quest to consolidate current knowledge on the early determinants of maternal and child health outcomes related to obesity, cardiovascular disease risk, and neurodevelopment. The primary goal was to delineate the relative influence of genetics and environmental factors, particularly in relation to specific nutrients and food components, on determinants of risk within the developmental stages of pregnancy, infancy (0-12 mo), and early childhood up to 5 y of age. A panel of experts was charged with critiquing the evidence presented and with identifying research gaps and challenges for future research, such as when and how the food industry might translate knowledge of the determinants of disease into improvements in human health through food product development.

As the rate of survival of premature infants isincreasing, more attention is necessarily focused onimproving the quality of survival through optimalnutritional management. The nutritional needs of the premature infant are greater than at any othertime in the life cycle. The benefits of human milk forterm infants are well known. Emerging data suggest thathuman milk may especially benefit the premature infant. The human milk-fed premature infant mayexperience improved health (such as lower rates ofinfection and necrotizing enterocolitis),gastrointestinal function, and neurodevelopment. Thesefactors may outweigh the concerns about adequategrowth, nutrient accretion, and biochemical indices ofnutritional status attributed to the lower nutrientcontent of human milk compared with preterm formula.Some of the nutritional concerns may be met by theuse of multinutrient supplements during the time infantsreceive tube-feeding, generally the time prior toattaining complete oral feeding in-hospital. The available data suggest that the quality ofsurvival of premature infants can be improved, both inthe short-term and long-term, through the feeding ofhuman milk.

(1) To determine whether nutrient malabsorption or inadequate nutrient intake were involved in the cause of growth delay in patients with bronchopulmonary dysplasia, and (2) to determine whether a nutrient-enriched formula given to infants with bronchopulmonary dysplasia to 3 months corrected age improves the rate of growth with greater lean and bone mass accretion when compared with infants fed an isoenergetic standard infant formula.A blinded, nutrition intervention trial of 60 preterm infants with bronchopulmonary dysplasia (birth weight, 866 +/- 169 g, gestational age, 26 +/- 1.5 weeks) randomized to either nutrient-enriched formula or standard formula. Growth, body composition, and nutrient retention were compared between groups by Student's t tests and analysis of covariance.Infants fed the enriched formula had significantly greater nitrogen and mineral retention at 38 weeks' postmenstrual age, and only the infants fed enriched formula had zinc retention similar to the intrauterine accretion. At 3 months corrected age infants fed enriched formula attained greater length (P.05), greater radial bone mineral content (P.01), and greater lean mass (P.01). The male infants in the enriched formula group had greater whole body bone mineral content than did male infants in the standard formula group (P = .02).Greater linear growth and lean and bone mass in the enriched formula group suggests that infants with bronchopulmonary dysplasia attain faster "catch-up" growth when fed higher intakes of protein, calcium, phosphorus, and zinc than provided in standard proprietary formulas.

Tamoxifen (Tam) has been shown to inhibit dexamethasone (Dex)-mediated effects on bone formation in vitro. Our objective was to determine whether Tam would block Dex-induced osteopenia and growth inhibition in growing piglets. Four-day-old male Yorkshire piglets were adapted to a liquid formula diet (400 ml/kg x day) and randomized to one of four groups (n = 5/group): Dex (0.5 mg/kg x day), Tam (1 mg/kg x day), Dex plus Tam, or placebo control (vehicle only). Both drugs were administered by orogastric gavage twice daily for 12 days. At baseline and at the end of treatment, whole body bone mineral density (BMD) was determined by dual energy x-ray absorptiometry (Hologic QDR1000W). Plasma osteocalcin and PTH were measured on days 0 and 12, and urinary N-telopeptide was measured on day 12. Changes in axial length and daily weight were also measured. Delta whole body BMD was 29% lower (P0.05) in Dex alone treated piglets than in controls (0.033 vs. 0.047 g/cm2, respectively), whereas the maximum change in BMD in Dex plus Tam group (0.046 g/cm2) was similar to that in controls. Concurrent Tam administration reduced the Dex-induced deficit in weight gain by 56% (P0.05) and the deficit in axial length gain by 72% (P0.01). In Dex alone treated piglets, PTH was significantly elevated (7-fold), whereas osteocalcin and N-telopeptide were significantly reduced compared with control values. These effects were prevented by Tam. These data suggest that the suppression of growth and other changes in parameters of bone metabolism induced by glucocorticoids in vivo can be attenuated by Tam.

Background Symptomatic osteopenia is a common form of morbidity in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. A causal role for corticosteroids has been proposed, but other investigators have suggested that cranial irradiation is an important factor contributing to this disorder. Procedure. In this study of children with ALL, all of whom received steroids, skeletal morbidity was assessed radiographically by an observer who was blinded to the ages of the children, their risk categorization (and related treatment), and the timing of the assessments with respect to the administration of therapy. Discussion. Skeletal morbidity was most prevalent in older subjects who had been given cranial radiotherapy. However, there was no difference in the frequency of fractures in two groups of younger children (⩽9 years of age), one irradiated and the other not. Conclusions. It is likely that corticosteroid therapy plays an important part in the pathogenesis of this disorder. The role played by cranial irradiation is much less certain. Med. Pediatr. Oncol. 30:347–350, 1998. © 1998 Wiley-Liss, Inc.