Publications by authors named "Angela M Devlin"

61 Publications

Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood.

Am J Physiol Regul Integr Comp Physiol 2021 11 6;321(5):R802-R811. Epub 2021 Oct 6.

Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.

Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long-term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments ( = 7-10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first 6 days of life with 0.2 mg/g body wt of respective treatments (24% solution; 1-4 μL/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 wk onto a control diet and fed until age 16 wk. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice ( ≤ 0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor-1 than adult water-treated female mice ( ≤ 0.05); these effects were not observed in males. Lower liver -adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared with water-treated female and male mice ( ≤ 0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared with water-treated female mice ( < 0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism.
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http://dx.doi.org/10.1152/ajpregu.00091.2021DOI Listing
November 2021

Greater Arterial Stiffness in Children with or without Second-generation Antipsychotic Treatment for Mental Health Disorders: Rigidité Artérielle Plus Importante Chez Les Enfants Avec ou Sans Traitement Par Antipsychotiques de la Deuxième Génération Pour des Troubles de Santé Mentale.

Can J Psychiatry 2021 07 2;66(7):667-676. Epub 2020 Dec 2.

Department of Pediatrics, BC Children's Hospital Research Institute, 8166The University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Second-generation antipsychotics (SGAs) are used for a variety of mental disorders and are associated with cardiometabolic side effects in children. The objective of this study was to assess the cardiovascular health of children with mental disorders that are SGA-treated or SGA-naive.

Methods: SGA-treated ( = 47) or SGA-naive ( = 37) children (aged 6 to 18 years) with mental disorders and control children ( = 83, no mental disorder) underwent assessment for cardiac function and morphology by echocardiography, aortic pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). Body mass index (BMI) -scores, waist circumference -scores, systolic and diastolic blood pressure (BP) percentiles for height and sex, and fasting plasma glucose, insulin, triglycerides, and cholesterol were also assessed. Differences between SGA-treated, SGA-naive, and control children were assessed by linear and log-linear regression models.

Results: SGA-treated children had greater BMI -scores and overweight/obesity (BMI ≥ 85th percentile for age and sex) and hypertension than SGA-naive and control children. The PWV geometric mean was 11.1% higher in SGA-treated (95%CI, 3.95 to 18.77) and 12.9% higher in SGA-naive children (95% CI, 5.60 to 20.59) compared to controls in models adjusted for age, sex, BMI, and systolic BP percentile. Left ventricular (LV) end-diastolic dimension/body surface area (BSA), LV end-systolic dimension/BSA, and LV ejection fraction were lower in SGA-treated and SGA-naive children compared to controls in models adjusted for sex and age.

Conclusions: Children with mental disorders have greater arterial stiffness and altered cardiac structure/function than children with no mental health diagnosis. SGA treatment in children is not associated with alterations in cardiovascular structure/function.
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http://dx.doi.org/10.1177/0706743720974838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243168PMC
July 2021

Daily Oral Supplementation with 60 mg of Elemental Iron for 12 Weeks Alters Blood Mitochondrial DNA Content, but Not Leukocyte Telomere Length in Cambodian Women.

Nutrients 2021 May 31;13(6). Epub 2021 May 31.

Food, Nutrition and Health, University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada.

There is limited evidence regarding the potential risk of untargeted iron supplementation, especially among individuals who are iron-replete or have genetic hemoglobinopathies. Excess iron exposure can increase the production of reactive oxygen species, which can lead to cellular damage. We evaluated the effect of daily oral supplementation on relative leukocyte telomere length (rLTL) and blood mitochondrial DNA (mtDNA) content in non-pregnant Cambodian women (18-45 years) who received 60 mg of elemental iron as ferrous sulfate ( = 190) or a placebo ( = 186) for 12 weeks. Buffy coat rLTL and mtDNA content were quantified by monochrome multiplex quantitative polymerase chain reaction. Generalized linear mixed-effects models were used to predict the absolute and percent change in rLTL and mtDNA content after 12 weeks. Iron supplementation was not associated with an absolute or percent change in rLTL after 12 weeks compared with placebo (ß-coefficient: -0.04 [95% CI: -0.16, 0.08]; 0.50 and ß-coefficient: -0.96 [95% CI: -2.69, 0.77]; 0.28, respectively). However, iron supplementation was associated with a smaller absolute and percent increase in mtDNA content after 12 weeks compared with placebo (ß-coefficient: -11 [95% CI: -20, -2]; = 0.02 and ß-coefficient: -11 [95% CI: -20, -1]; = 0.02, respectively). Thus, daily oral iron supplementation for 12 weeks was associated with altered mitochondrial homeostasis in our study sample. More research is needed to understand the risk of iron exposure and the biological consequences of altered mitochondrial homeostasis in order to inform the safety of the current global supplementation policy.
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http://dx.doi.org/10.3390/nu13061877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227094PMC
May 2021

Detectable Unmetabolized Folic Acid and Elevated Folate Concentrations in Folic Acid-Supplemented Canadian Children With Sickle Cell Disease.

Front Nutr 2021 21;8:642306. Epub 2021 Apr 21.

Food, Nutrition, and Health, The University of British Columbia, Vancouver, BC, Canada.

Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a variant (rs344) in the gene encoding the β-globin subunit of hemoglobin. Chronic hemolytic anemia and increased erythropoiesis and RBC turnover in individuals with SCD can result in increased needs for folate and other B-vitamins. We assessed B-vitamin status, and the distribution of folate forms, including unmetabolized folic acid (UMFA), in Canadian children with SCD supplemented with 1 mg/d folic acid (current routine practice). Non-fasted serum and plasma samples were analyzed for concentrations of folate, and vitamins B-2, B-6, and B-12. Eleven individuals (45% male; SCD type: HbSS = 8, HbSC = 2, HbSβ-Thal = 1), with a median (IQR) age of 14 (7, 18) years, were included. Total folate concentrations were 3-27 times above the deficiency cut-off (10 nmol/L), and 64% of children had elevated folate levels (>45.3 nmol/L). UMFA (>0.23 nmol/L) was detected in all children, and 36% of participants had elevated levels of UMFA (>5.4 nmol/L). All children were vitamin B-12 sufficient (>150 pmol/L), and the majority (55%) had sufficient B-6 status (>30 nmol/L). Among this sample of Canadian children with SCD, there was limited evidence of B-vitamin deficiencies, but UMFA was detectable in all children.
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http://dx.doi.org/10.3389/fnut.2021.642306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096995PMC
April 2021

Dietary Riboflavin Intake and Riboflavin Status in Young Adult Women Living in Metro Vancouver, Canada.

Curr Dev Nutr 2021 Apr 13;5(4):nzab021. Epub 2021 Mar 13.

Women and Kids Theme, South Australian Health and Medical Research Institute, and Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.

Background: Nutrition surveys suggest that <10% of Canadian adults have inadequate riboflavin intakes. However, biochemical riboflavin deficiency [erythrocyte glutathione reductase activity coefficient (EGRac) ≥1.40] has been reported in 41% of young adult women living in Metro Vancouver. Canadian Chinese ethnicity comprise >25% of Vancouver's population and are postulated to have poorer riboflavin status than those of European ethnicity because they could be less likely to consume dairy products and fortified wheat.

Objectives: The objectives of this study were to determine dietary riboflavin intake and food sources, and to assess the association between riboflavin intake and status in young women of European (= 107) and Chinese (= 91) ethnicities living in Metro Vancouver, Canada.

Methods: This was a cross-sectional study conducted in women (aged 19-45 y). Women were healthy, not pregnant or breastfeeding, of European or Chinese ethnicities, and not taking riboflavin-containing supplements for the past 4 mo. Dietary riboflavin intake was assessed using the past-year Diet History Questionnaire II, and riboflavin status (EGRac) was measured in fasting venous blood samples.

Results: Only 7% of participants had dietary riboflavin intakes below the Estimated Average Requirement (0.9 mg/d), but 40% of women had biochemical riboflavin deficiency (EGRac ≥1.40). Although more Canadian women of European ethnicity than Chinese ethnicity had biochemical riboflavin deficiency (46% and 34%;  < 0.001), median dietary riboflavin intake did not differ (1.73 and 1.82 mg/d; = 0.587). Dairy products and vegetables contributed the most to riboflavin intake. Energy-adjusted dietary riboflavin intake was inversely associated with EGRac (B = -0.04, 95% CI: -0.07, -0.01). However, after further adjustment the relation was not significant.

Conclusions: Overall, women of reproductive age living in Metro Vancouver, Canada, had a low prevalence of inadequate dietary riboflavin intake despite the high prevalence of apparent biochemical riboflavin deficiency.
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http://dx.doi.org/10.1093/cdn/nzab021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035065PMC
April 2021

Treatment-related weight gain and metabolic complications in children with mental health disorders: potential role for lifestyle interventions.

Appl Physiol Nutr Metab 2021 Mar 23;46(3):193-204. Epub 2020 Nov 23.

Department of Pediatrics, The University of British Columbia and BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada.

Over 1 million Canadian children are estimated to have a mental health disorder, which are commonly treated with medications, such as second-generation antipsychotics (SGAs). Estimates suggest that SGA prescriptions to children are increasing in Canada. Although these medications are important and lifesaving components of psychiatric treatment, they are not without side effects. For some children, SGA treatment is associated with adverse metabolic complications including rapid weight gain, dyslipidemia, elevated blood pressure, and risk for type 2 diabetes. It is not clear why these complications develop, but it is assumed that SGAs stimulate appetite and food intake, and reduce resting energy expenditure leading to weight gain and that the metabolic complications occur secondary to the weight gain. Understanding the mechanisms underlying these complications is key to being able to identify children at risk and prevent and optimize treatment. In this narrative review, we provide an overview of the literature pertaining to the weight gain and metabolic complications in children treated with SGAs, highlighting the scope of the problem and the current limited research on how diet and physical activity can be used to prevent or lessen the severity of the metabolic complications and improve the long-term health trajectories of SGA-treated children. Children are increasingly being treated with second-generation antipsychotics for mental health disorders. Dietary and physical activity assessments are not commonly considered in clinical settings. Randomized controlled trials of lifestyle interventions are needed to determine the effectiveness of mitigating the cardiometabolic complications in second-generation antipsychotic-treated children.
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http://dx.doi.org/10.1139/apnm-2020-0259DOI Listing
March 2021

Exercise during pregnancy mitigates the adverse effects of maternal obesity on adult male offspring vascular function and alters one-carbon metabolism.

Physiol Rep 2020 09;8(18):e14582

Department of Pathology and Laboratory Medicine, The University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Maternal obesity during pregnancy can adversely affect adult offspring vascular endothelial function. This study examined whether maternal exercise during pregnancy and lactation mitigates the adverse effects of maternal obesity on offspring vascular endothelial function. Female (C57BL/6N) mice were fed from weaning a control diet (10% kcal fat) or western diet (45% kcal fat) to induce excess adiposity (maternal obesity). After 13 weeks, the female mice were bred and maintained on the diets, with and without access to a running wheel (exercise), throughout breeding, pregnancy, and lactation. Offspring were weaned onto the control or western diet and fed for 13 weeks; male offspring were studied. Maternal exercise prevented the adverse effects of maternal obesity on offspring vascular endothelial function. However, this was dependent on offspring diet and the positive effect of maternal exercise was only observed in offspring fed the western diet. This was accompanied by alterations in aorta and liver one-carbon metabolism, suggesting a role for these pathways in the improved endothelial function observed in the offspring. Obesity and exercise had no effect on endothelial function in the dams but did affect aorta and liver one-carbon metabolism, suggesting the phenotype observed in the offspring may be due to obesity and exercise-induced changes in one-carbon metabolism in the dams. Our findings demonstrate that maternal exercise prevented vascular dysfunction in male offspring from obese dams and is associated with alterations in one-carbon metabolism.
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http://dx.doi.org/10.14814/phy2.14582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518297PMC
September 2020

Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial.

Trials 2020 Jun 29;21(1):593. Epub 2020 Jun 29.

Food, Nutrition, and Health, Faculty of Land and Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada.

Background: Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1-5 mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs. In animal and human studies, high folic acid intakes (1 mg/d) have been associated with accelerated growth of some cancers, and the biological effects of circulating unmetabolized folic acid (UMFA), which can occur with doses of folic acid ≥ 0.2 mg/d, are not fully understood. The objective of this study is to determine efficacy of, and alterations in folate metabolism from high-dose folic acid in children with SCD during periods of folic acid supplementation versus no supplementation.

Methods: In this double-blind randomized controlled cross-over trial, children with SCD (n = 36, aged 2-19 years) will be randomized to either receive 1 mg/d folic acid, the current standard of care, or a placebo for 12 weeks. After a 12-week washout period, treatments will be reversed. Total folate concentrations (serum and RBC), different folate forms (including UMFA), folate-related metabolites, and clinical outcomes will be measured at baseline and after treatment periods. The sum of the values measured in the two periods will be calculated for each subject and compared across the two sequence groups by means of a test for independent samples for the primary (RBC folate concentrations) and secondary (UMFA) outcomes. Dietary intake will be measured at the beginning of each study period.

Discussion: As the first rigorously designed clinical trial in children with SCD, this trial will inform and assess current clinical practice, with the ultimate goal of improving nutritional status of children with SCD.

Trial Registration: ClinicalTrials.gov NCT04011345 . Registered on July 8, 2019.
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http://dx.doi.org/10.1186/s13063-020-04540-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325072PMC
June 2020

Sheila M. Innis, PhD, RD (1953-2016): A Pioneer and Innovator Influencing the Maternal and Infant Nutrition Field.

J Nutr 2020 07;150(7):1673-1675

Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

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http://dx.doi.org/10.1093/jn/nxaa078DOI Listing
July 2020

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study.

Trials 2020 May 5;21(1):380. Epub 2020 May 5.

Food, Nutrition and Health, Faculty of Land and Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC, V6T 1Z4, Canada.

Background: North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in the circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins; however, it has yet to be evaluated during pregnancy.

Methods/design: This double-blind, randomized trial will recruit 60 pregnant women aged 19-42 years. The women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16 weeks. The trial will be initiated at 8-21 weeks' gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1 week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations.

Discussion: This proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women.

Trial Registration: ClinicalTrials.gov, ID: NCT04022135. Registered on 14 July 2019.
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http://dx.doi.org/10.1186/s13063-020-04320-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201521PMC
May 2020

Ambulatory blood pressure and carotid intima media thickness in children with type 1 diabetes.

Pediatr Diabetes 2020 03 26;21(2):358-365. Epub 2019 Dec 26.

Department of Pediatrics, The University of British Columbia, BC Children's Hospital Research Institute, Vancouver, Canada.

Background/objective: Blood pressure abnormalities may play an important role in macrovascular damage in type 1 diabetes. Little is known about blood pressure abnormalities and macrovascular damage in children with type 1 diabetes.

Methods: Children with type 1 diabetes (n = 57) for a short (3 months-2 years; n = 24) or long duration (≥5 years; n = 33) and a group of control children without diabetes (n = 29) completed 24-h ambulatory blood pressure monitoring (ABPM). Carotid intima media thickness (cIMT), a subclinical indicator of atherosclerosis, was assessed by carotid ultrasound.

Results: ABPM abnormalities were more prevalent (57% vs 24%, respectively), and daytime, nighttime and 24-h systolic, diastolic, and mean arterial blood pressure indices were higher in children with type 1 diabetes compared to control children. The odds estimate of an ABPM abnormality was 6.68 (95% confidence interval: 1.95, 22.9; P = .003) in children with type 1 diabetes compared to controls after adjusting for age, sex, and BMI standardized for age and sex (zBMI). An interaction between ABPM and zBMI on cIMT was observed. In children with type 1 diabetes and ABPM abnormalities, every 1 SD increase in zBMI was associated with a 0.030 mm increase in cIMT (95% confidence interval: 0.002, 0.041; P = .031). This was not observed in control children with ABPM abnormalities or in children with normal ABPM, regardless of type 1 diabetes status.

Conclusions: Children with type 1 diabetes have a high prevalence of ABPM abnormalities independent of disease duration and this is related to early indicators of cardiovascular damage.
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http://dx.doi.org/10.1111/pedi.12960DOI Listing
March 2020

Biomarkers of Docosahexaenoic Acid but Not Arachidonic Acid Reflect Dietary Intakes in Toddlers at Ages 1 and 2 Years Who Are Not Meeting Dietary Recommendations.

J Nutr 2020 03;150(3):518-525

Department of Pediatrics, The University of British Columbia and BC Children's Hospital Research Institute, Vancouver, Canada.

Background: Long-chain n-6 and n-3 PUFAs are important for growth and development. However, little is known about requirements and current dietary intakes of these fatty acids in toddlers.

Objectives: This study assessed dietary intakes of n-6 and n-3 PUFAs and determined the relation to circulating PUFAs in toddlers at ages 1 and 2 y.

Methods: This is a secondary analysis of data from toddlers enrolled in a double-blind randomized controlled trial of arachidonic acid (ARA) and DHA supplementation between ages 1 and 2 y. Dietary intakes of fatty acids were estimated by 3-d food records, and fatty acid composition in plasma total phospholipids, red blood cell phosphatidylethanolamine (PE), and phosphatidylcholine (PC) were assessed by GC at baseline in all subjects (n = 110; mean age 1.12 y; 64% male) and in the control subjects at 2 y (n = 43).

Results: The dietary intakes of ARA, EPA, and DHA at age 1 y (baseline) were [mean (median)] 36.8 (30.0), 16.0 (0.00), and 31.1 (10.0) mg/d, respectively. Dietary intakes increased to 52.7 (45.0), 35.8 (0.00), and 64.8 (20.0) mg/d, respectively, at age 2 y (P < 0.05). The predominant dietary source of EPA and DHA was fish/seafood; eggs were an important source of ARA and DHA. Dietary DHA intakes were positively associated with plasma PE and PC DHA (P < 0.05). No relations between dietary ARA intakes and plasma PE and PC ARA (P > 0.05) were observed.

Conclusions: These findings suggest that most toddlers are not meeting the recommendation for dietary PUFA intakes and that higher dietary DHA intakes are reflected in plasma PE and PC DHA composition. Further work is required to investigate a biomarker for dietary ARA intake. This trial is registered at clinicaltrials.gov as NCT01263912.
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http://dx.doi.org/10.1093/jn/nxz280DOI Listing
March 2020

Suboptimal Biochemical Riboflavin Status Is Associated with Lower Hemoglobin and Higher Rates of Anemia in a Sample of Canadian and Malaysian Women of Reproductive Age.

J Nutr 2019 11;149(11):1952-1959

Department of Food, Nutrition, and Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood.

Objectives: We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia.

Methods: Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n = 206) and Malaysia (n = 210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia.

Results: EGRac (mean ± SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49 ± 0.17 compared with 1.38 ± 0.11). Likewise, riboflavin biomarker deficiency (EGRac ≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n = 416), EGRac values were negatively associated with hemoglobin concentration (r = -0.18; P < 0.001). This relation remained significant (P = 0.029) after adjusting for age, parity, ethnicity, vitamin B-12, folate, sTfR, ferritin, and vitamin A. Women with riboflavin deficiency (EGRac ≥1.40) were twice as likely to present with anemia (adjusted OR: 2.38; 95% CI: 1.08, 5.27) compared with women with EGRac <1.40.

Conclusions: Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation.
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http://dx.doi.org/10.1093/jn/nxz151DOI Listing
November 2019

Impact of Prenatal Selective Serotonin Reuptake Inhibitor Antidepressant Exposure and Maternal Mood on Physical Activity, Dietary Intake, and Markers of Adiposity at Age 6 Years.

J Dev Behav Pediatr 2019 05;40(4):266-274

Department of Pediatrics, University of British Columbia, BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Objective: This study assessed associations between maternal depressive symptoms, prenatal maternal antidepressant treatment, maternal estimates of child physical activity (PA), dietary total intake, and markers of adiposity.

Methods: Mothers and their children (N = 116) were part of a longitudinal cohort study examining the effects of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants and maternal depression (SSRI exposed, n = 42; nonexposed, n = 74). Maternal depression symptoms were assessed prenatally and postnatally. At 6 years, PA was assessed using maternal report, 3-day dietary total intakes were obtained using objective records of intake, portion sizes, and product brand names, and birth weight, weight, height, and waist circumference (WC) at age 6 years were also collected. Body mass index (BMI) and WC z-scores standardized for sex and age were computed as markers of adiposity.

Results: Children with SSRI exposure had lower levels of PA than children without SSRI exposure. Total dietary energy intakes did not vary between exposure groups. SSRI exposure was not associated with BMI or WC z-scores of the children. Importantly, although lower birth weight was observed in SSRI-exposed children, differences did not remain, accounting for gestational age.

Conclusion: Although SSRI exposure was associated with lower estimates of PA, such exposure was not associated with markers of adiposity or total diet energy intake at age 6 years. The implications across subsequent measures in childhood remain to be determined.
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http://dx.doi.org/10.1097/DBP.0000000000000658DOI Listing
May 2019

CHIPS-Child: Testing the developmental programming hypothesis in the offspring of the CHIPS trial.

Pregnancy Hypertens 2018 Oct 19;14:15-22. Epub 2018 May 19.

Obstetrics and Gynaecology, Universite de Sherbrooke, Canada. Electronic address:

Objectives: As a follow-up to the CHIPS trial (Control of Hypertension In Pregnancy Study) of 'less tight' (versus 'tight') control of maternal blood pressure in pregnancy, CHIPS-Child investigated potential developmental programming of maternal blood pressure control in pregnancy, by examining measures of postnatal growth rate and hypothalamic-pituitary adrenal (HPA) axis activation.

Methods: CHIPS follow-up was extended to 12 ± 2 months corrected post-gestational age for anthropometry (weight, length, head/waist circumference). For eligible children with consent for a study visit, we collected biological samples (hair/buccal samples) to evaluate HPA axis function (hair cortisol levels) and epigenetic change (DNA methylation analysis of buccal cells). The primary outcome was 'change in z-score for weight' between birth and 12 ± 2 mos. Secondary outcomes were hair cortisol and genome-wide DNA methylation status.

Results: Of 683 eligible babies, 183 (26.8%) were lost to follow-up, 83 (12.2%) declined, 3 (0.4%) agreed only to ongoing contact, and 414 (60.6%) consented. 372/414 (89.9%) had weight measured at 12mos. In 'less tight' (vs. 'tight') control, the primary outcome was similar [-0.26 (-0.53, +0.01); p = 0.14, p = 0.06]; median (95% confidence interval) hair cortisol (N = 35 samples) was lower [-496 (-892, -100) ng/g; p = 0.02], and buccal swab DNA methylation (N = 16 samples) was similar. No differences in growth rate could be demonstrated up to 5 years.

Conclusions: Results demonstrate no compelling evidence for developmental programming of growth or the HPA axis. Clinicians should look to the clinical findings of CHIPS to guide practice. Researchers should seek to replicate these findings and extend outcomes to paediatric blood pressure and neurodevelopment.
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http://dx.doi.org/10.1016/j.preghy.2018.04.021DOI Listing
October 2018

Risperidone But Not Quetiapine Treatment Is Associated With Increased Appetite But Not Satiety Hormones in Children During An Oral Glucose Tolerance Test: A Pilot Study.

J Clin Psychopharmacol 2018 Dec;38(6):622-626

From the Department of Paediatrics, University of British Columbia, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.

Background: Second-generation antipsychotics (SGAs) are commonly used to treat children with mental health conditions (MHCs) but are associated with adverse effects including obesity, hypertension, dyslipidemia, and type 2 diabetes. The mechanisms underlying these complications are unknown, but it has been suggested that SGAs increase appetite leading to weight gain. The present objective was to perform a pilot study to investigate appetite and satiety hormones in SGA-treated (risperidone or quetiapine) and SGA-naive children with similar mental health conditions.

Methods: Oral glucose tolerance tests (OGTTs) were conducted in SGA-naive (n = 18), risperidone-treated (n = 20), and quetiapine-treated (n = 16) children recruited from the British Columbia Children's Hospital Psychiatry Department. Over 5 time-points during the OGTT, appetite questionnaires using a visual analogue scale were administered, and blood was collected to measure ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, glucagon-like protein 1, leptin, and adiponectin. Mixed model analyses were conducted to examine between-group differences.

Results: The children were similar in age, psychiatric diagnosis, and global assessment of functioning scores. Body mass index z-scores were also similar between groups. Appetite was increased during the OGTT in the risperidone-treated compared with the SGA-naive group for 2 questions ("How strong is your desire to eat"; P = 0.003 and "How much food do you think you can eat"; P = 0.028). No differences in satiety hormones were observed between the 3 groups.

Conclusions: Risperidone treatment in youth is associated with elevated appetite during an OGTT, with no differences in gut peptides or adipocytokines to explain risperidone's effect on appetite. Further research is needed to explore other mediators of weight gain and metabolic dysfunction in SGA-treated youth.
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http://dx.doi.org/10.1097/JCP.0000000000000956DOI Listing
December 2018

Children's stress regulation mediates the association between prenatal maternal mood and child executive functions for boys, but not girls.

Dev Psychopathol 2018 08;30(3):953-969

University of British Columbia,BC Children's Hospital Research Institute.

Prenatal exposure to maternal mood disturbances shapes children's cognitive development reflected in the critical construct of executive functions (EFs). Little is known, however, about underlying mechanisms. By examining cortisol responses in both everyday and lab challenge settings, we tested whether the child/offspring hypothalamic-pituitary-adrenal axis mediates effects of prenatal maternal mood on child EFs at age 6. In 107 Canadian children born to women with a wide range of anxious and depressive symptoms during pregnancy, we found that in boys but not girls, depressed and/or anxious prenatal maternal mood is associated with heightened diurnal cortisol levels in everyday settings, as well as heightened cortisol reactivity to a lab challenge and that this heightened reactivity was associated with poorer EFs. Among boys we also observed that cortisol reactivity but not diurnal cortisol mediated the association between depressed and/or anxious prenatal maternal mood and EFs. Depressed and/or anxious prenatal maternal mood was related to child EFs for both girls and boys. To our knowledge, this is the first study to demonstrate a mediating role for child stress regulation in the association between prenatal maternal stress-related mood disturbances and child EFs, providing evidence of a mechanism contributing to fetal programming of cognition.
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http://dx.doi.org/10.1017/S095457941800041XDOI Listing
August 2018

Plasma Betaine Is Positively Associated with Developmental Outcomes in Healthy Toddlers at Age 2 Years Who Are Not Meeting the Recommended Adequate Intake for Dietary Choline.

J Nutr 2018 08;148(8):1309-1314

Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver, Canada.

Background: Choline is an important nutrient during development. However, there are limited data on dietary choline intake and status in toddlers and the relation to neurodevelopmental outcomes.

Objective: This study assessed dietary choline intake and status in healthy toddlers at ages 1 and 2 y and determined the relation to neurodevelopmental outcomes.

Methods: This is a secondary analysis of data from healthy toddlers enrolled in a double-blind, randomized controlled trial of long-chain polyunsaturated fatty acid supplementation between ages 1 and 2 y. Dietary intakes of betaine and choline were estimated by 3-d food records; plasma free choline, betaine, and dimethylglycine were quantified by liquid chromatography-tandem mass spectrometry. Developmental outcomes were assessed at age 2 y with the use of the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), Cognitive and Language composites, and the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI).

Results: The mean ± SD daily intake for total choline at age 1 y was 174 ± 56.2 mg/d and increased (P < 0.001) to 205 ± 67.5 mg/d at age 2 y. At ages 1 and 2 y, 71.8% and 55.8%, respectively, of toddlers did not meet the recommended 200-mg/d Adequate Intake (AI) for dietary choline. At age 1 y, mean ± SD plasma free choline, betaine, and dimethylglycine concentrations were 10.4 ± 3.3, 41.1 ± 15.4, and 4.1 ± 1.9 µmol/L, respectively. Plasma free choline (8.5 ± 2.3 µmol/L) and dimethylglycine (3.2 ± 1.3 µmol/L) concentrations were lower (P < 0.001) at age 2 y. Plasma betaine concentrations were positively associated with the Beery-VMI (β = 0.270; 95% CI: 0.026, 0.513; P = 0.03) at age 2 y.

Conclusions: These findings suggest that most toddlers are not meeting the recommended AI for dietary choline and that higher plasma betaine concentrations are associated with better visual-motor development at age 2 y. Further work is required to investigate choline metabolism and its role in neurodevelopment in toddlers. The trial is registered at clinicaltrials.gov as NCT01263912.
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http://dx.doi.org/10.1093/jn/nxy108DOI Listing
August 2018

Maternal folic acid supplementation with vitamin B deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet.

FASEB J 2018 09 17;32(9):5039-5050. Epub 2018 Apr 17.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Epidemiologic studies have reported relationships between maternal high folate and/or low B status during pregnancy and greater adiposity and insulin resistance in children. The goal of this study was to determine the effects of maternal folic acid supplementation (10 mg/kg diet), with (50 μg/kg diet) and without B, on adult female offspring adiposity and glucose homeostasis. Female C57BL/6J mice were fed 1 of 3 diets from weaning and throughout breeding, pregnancy, and lactation: control (2 mg/kg diet folic acid, 50 μg/kg diet B), supplemental folic acid with no B (SFA-B), or supplemental folic acid with adequate B (SFA+B). Female offspring were weaned onto the control diet or a Western diet (45% energy fat, 2 mg/kg diet folic acid, 50 μg/kg diet B) for 35 wk. After weaning, control diet-fed offspring with SFA-B dams had fasting hyperglycemia, glucose intolerance, lower β cell mass, and greater islet hepatocyte nuclear factor 1 homeobox α and nuclear receptor subfamily 1 group H member 3 mRNA than did offspring from control dams. In Western diet-fed offspring, those with SFA-B dams had lower fasting blood glucose and plasma insulin concentrations, and were smaller than control offspring. Our findings suggest that maternal folic acid supplementation with B deficiency during pregnancy/lactation programs the metabolic health of adult female offspring but is dependent on offspring diet.-Henderson, A. M., Tai, D. C., Aleliunas, R. E., Aljaadi, A. M., Glier, M. B., Xu, E. E., Miller, J. W., Verchere, C. B., Green, T. J., Devlin, A. M. Maternal folic acid supplementation with vitamin B deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet.
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http://dx.doi.org/10.1096/fj.201701503RRDOI Listing
September 2018

l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women.

J Nutr 2018 06;148(6):885-890

Departments of Pediatrics, Food, Nutrition & Health, and Pathology & Laboratory Medicine, University of British Columbia, BC Children's Hospital Research Institute, Vancouver, Canada.

Background: Folic acid fortification of grains is mandated in many countries to prevent neural tube defects. Concerns regarding excessive intakes of folic acid have been raised. A synthetic analog of the circulating form of folate, l-5-methyltetrahydrofolate (l-5-MTHF), may be a potential alternative.

Objective: The objective of this study was to determine the effects of folic acid or l-5-MTHF supplementation on blood folate concentrations, methyl nutrient metabolites, and DNA methylation in women living in Malaysia, where there is no mandatory fortification policy.

Methods: In a 12-wk, randomized, placebo-controlled intervention trial, healthy Malaysian women (n = 142, aged 20-45 y) were randomly assigned to receive 1 of the following supplements daily: 1 mg (2.27 μmol) folic acid, 1.13 mg (2.27 μmol) l-5-MTHF, or a placebo. The primary outcomes were plasma and RBC folate and vitamin B-12 concentrations. Secondary outcomes included plasma total homocysteine, total cysteine, methionine, betaine, and choline concentrations and monocyte long interspersed nuclear element-1 (LINE-1) methylation.

Results: The folic acid and l-5-MTHF groups had higher (P < 0.001) RBC folate (mean ± SD: 1498 ± 580 and 1951 ± 496 nmol/L, respectively) and plasma folate [median (25th, 75th percentiles): 40.1 nmol/L (24.9, 52.7 nmol/L) and 52.0 nmol/L (42.7, 73.1 nmol/L), respectively] concentrations compared with RBC folate (958 ± 345 nmol/L) and plasma folate [12.6 nmol/L (8.80, 17.0 nmol/L)] concentrations in the placebo group at 12 wk. The l-5-MTHF group had higher RBC folate (1951 ± 496 nmol/L; P = 0.003) and plasma folate [52.0 nmol/L (42.7, 73.1 nmol/L); P = 0.023] at 12 wk than did the folic acid group [RBC folate, 1498 ± 580 nmol/L; plasma folate, 40.1 nmol/L (24.9, 52.7 nmol/L)]. The folic acid and l-5-MTHF groups had 17% and 15%, respectively, lower (P < 0.001) plasma total homocysteine concentrations than did the placebo group at 12 wk; there were no differences between the folic acid and l-5-MTHF groups. No differences in plasma vitamin B-12, total cysteine, methionine, betaine, and choline and monocyte LINE-1 methylation were observed.

Conclusion: These findings suggest differential effects of l-5-MTHF compared with folic acid supplementation on blood folate concentrations but no differences on plasma total homocysteine lowering in Malaysian women. This trial was registered at clinicaltrials.gov as NCT01584050.
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http://dx.doi.org/10.1093/jn/nxy057DOI Listing
June 2018

Diet and cardiometabolic side effects in children treated with second-generation antipsychotics.

Clin Nutr ESPEN 2018 02 17;23:205-211. Epub 2017 Oct 17.

Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital Research Institute, Vancouver, Canada. Electronic address:

Background: Second-generation antipsychotic (SGA) treatment in children is associated with metabolic side effects including weight gain, dyslipidemia, and insulin resistance. The objective of this study is to determine if SGA treatment in children affects dietary intakes and relationship to metabolic side effects.

Methods: Three-day food records assessed dietary energy and macronutrient intakes in a cross-sectional population of SGA-treated (n = 35) and SGA-naïve (n = 29) children.

Results: SGA-treated children had more overweight/obesity (BMI ≥ 85th percentile for age and sex, p = 0.001); waist circumference (WC) ≥ 90th percentile for age and sex (p = 0.007); waist:height ratio (WHtR) ≥ 85th percentile for age and sex (p = 0.004), greater HOMA-IR, (p = 0.001) and plasma triglycerides (p = 0.017), and lower plasma HDL (p = 0.029). Dietary energy intakes were not different between SGA-naïve and SGA-treated children [1734 ± 486 vs 1971 ± 649 (-135, 408) kcal/day, mean ± SD (95% CI)] after adjustments for sex, age, Tanner stage, psychostimulant use, and height. Similarly, no differences in macronutrient intakes were observed. In models adjusted for SGA treatment and physical activity, no relationships between dietary intakes and BMI were found, but dietary total energy intakes were positively associated with waist circumference z-scores (p = 0.019), systolic blood pressure z-scores (p = 0.028, also adjusted for BMI) and HOMA-IR (p = 0.013, also adjusted for age, sex, BMI). All of the children had poor diets with 87.5% having >7% of daily energy from saturated fat; 62.5% having >20% of daily energy from sugar; and almost 60% having sodium intakes above the tolerable upper intake level.

Conclusions: SGA treatment is not associated with greater dietary energy intakes in children. However, dietary energy intakes are associated with greater waist circumference and systolic blood pressure z-scores and HOMA-IR in children with mental health conditions.
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http://dx.doi.org/10.1016/j.clnesp.2017.09.013DOI Listing
February 2018

Comparison of a New Multiplex Immunoassay for Measurement of Ferritin, Soluble Transferrin Receptor, Retinol-Binding Protein, C-Reactive Protein and α¹-Acid-glycoprotein Concentrations against a Widely-Used s-ELISA Method.

Diagnostics (Basel) 2018 Feb 2;8(1). Epub 2018 Feb 2.

GroundWork, Fläsch 7306, Switzerland.

Recently, a multiplex ELISA (Quansys Biosciences) was developed that measures ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), C-reactive protein (CRP), α¹-acid glycoprotein (AGP), thyroglobulin, and histidine-rich protein 2. Our primary aim was to conduct a method-comparison study to compare five biomarkers (ferritin, sTfR, RBP, CRP, and AGP) measured with the Quansys assay and a widely-used s-ELISA (VitMin Lab, Willstaett, Germany) with use of serum samples from 180 women and children from Burkina Faso, Cambodia, and Malaysia. Bias and concordance were used to describe the agreement in values measured by the two methods. We observed poor overall agreement between the methods, both with regard to biomarker concentrations and deficiency prevalence estimates. Several measurements were outside of the limit of detection with use of the Quansys ELISA (total = 42 for ferritin, = 2 for sTfR, = 0 for AGP, = 5 for CRP, = 22 for RBP), limiting our ability to interpret assay findings. Although the Quansys ELISA has great potential to simplify laboratory analysis of key nutritional and inflammation biomarkers, there are some weaknesses in the procedures. Overall, we found poor comparability of results between methods. Besides addressing procedural issues, additional validation of the Quansys against a gold standard method is warranted for future research.
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http://dx.doi.org/10.3390/diagnostics8010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871996PMC
February 2018

Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial.

Nutrients 2017 Sep 6;9(9). Epub 2017 Sep 6.

Department of Pediatrics, University of British Columbia, BC Children's Hospital Research Institute, A4-194 950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada.

Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers ( = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21-9.00), B (95% CI), = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10-17.94), < 0.001) and girls (11.19 (4.69-17.68), = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.
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http://dx.doi.org/10.3390/nu9090975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622735PMC
September 2017

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

J Nutr 2017 09 2;147(9):1785-1794. Epub 2017 Aug 2.

Food, Nutrition, and Health and

Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. A- deficiency is characterized by the co-inheritance of 376 and 202 variants and is common in sub-Saharan Africa. We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect variants and α-thalassemia deletions. Overall, 11% of children had a sickle cell variant, 19% of boys were A- hemizygotes, 12% and 10% of girls were A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that A- hemizygous boys and 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. We found that 2 variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.
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http://dx.doi.org/10.3945/jn.117.252635DOI Listing
September 2017

The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial.

Am J Clin Nutr 2017 Jul 10;106(1):233-244. Epub 2017 May 10.

Discipline of Paediatrics, University of Adelaide, Adelaide, Australia; and

Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy. We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic. In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction ( = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) ( < 0.001) among women who received iron ( = 407) and 1.2 g/L (-0.6, 3.0 g/L) ( = 0.18) among women who received MMNs ( = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively. Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375.
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http://dx.doi.org/10.3945/ajcn.116.140996DOI Listing
July 2017

Prevalence and Predictors of Low Vitamin B6 Status in Healthy Young Adult Women in Metro Vancouver.

Nutrients 2016 Sep 1;8(9). Epub 2016 Sep 1.

Food Nutrition and Health, Faculty of Land and Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada.

Low periconceptional vitamin B6 (B6) status has been associated with an increased risk of preterm birth and early pregnancy loss. Given many pregnancies are unplanned; it is important for women to maintain an adequate B6 status throughout reproductive years. There is limited data on B6 status in Canadian women. This study aimed to assess the prevalence of B6 deficiency and predictors of B6 status in young adult women in Metro Vancouver. We included a convenience sample of young adult non-pregnant women (19-35 years; n = 202). Vitamin B6 status was determined using fasting plasma concentrations of pyridoxal 5'-phosphate (PLP). Mean (95% confidence interval) plasma PLP concentration was 61.0 (55.2, 67.3) nmol/L. The prevalence of B6 deficiency (plasma PLP < 20 nmol/L) was 1.5% and that of suboptimal B6 status (plasma PLP = 20-30 nmol/L) was 10.9%. Body mass index, South Asian ethnicity, relative dietary B6 intake, and the use of supplemental B6 were significant predictors of plasma PLP. The combined 12.4% prevalence of B6 deficiency and suboptimal status was lower than data reported in US populations and might be due to the high socioeconomic status of our sample. More research is warranted to determine B6 status in the general Canadian population.
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http://dx.doi.org/10.3390/nu8090538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037525PMC
September 2016

Sculpting infant soothability: the role of prenatal SSRI antidepressant exposure and neonatal SLC6A4 methylation status.

Dev Psychobiol 2016 09 2;58(6):745-58. Epub 2016 Jun 2.

Department of Pediatrics, University of British Columbia, Child and Family Research Institute, Vancouver, British Columbia, Canada.

The role of prenatal Selective Serotonin Reuptake Inhibitor (SSRI) exposure and SLC6A4 promoter methylation status in shaping soothability at 3 and 6 months of age, for infants exposed to antidepressant medication prenatally (n = 46) and those not exposed (n = 69) was investigated. SSRI exposure status and duration of exposure (number of days) were examined along with neonatal methylation status at mean CpG 9,10 and via factor analysis across 10 CpG sites yielding PC1 (CpGs sites: 3,4,5,7) and PC2 (CpG 1,8). Analyses revealed interactions for methylation markers and SSRI exposure variables. A significant interaction between SSRI exposure and mean SLC6A4 methylation at CpG 9,10 and separately for PC1 emerged, controlling for multiple birth/medical and background covariates (e.g., Apgar scores, maternal education). Increased neonatal methylation status was associated with increased soothability changes from 3 to 6 months among infants prenatally exposed to SSRIs.
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http://dx.doi.org/10.1002/dev.21414DOI Listing
September 2016

Folic Acid Supplementation of Female Mice, with or without Vitamin B-12, before and during Pregnancy and Lactation Programs Adiposity and Vascular Health in Adult Male Offspring.

J Nutr 2015 Apr;146(4):688-696

Department of Pathology and Laboratory Medicine, Child and Family Research Institute, Vancouver, Canada.

Background: The developmental origins of health and disease theory suggest that disturbances in the fetal and early postnatal environment contribute to chronic adulthood diseases, such as type 2 diabetes and cardiovascular disease. Greater adiposity and insulin resistance have been reported in children of women with high erythrocyte folate but poor vitamin B-12 status during pregnancy. The mechanisms underlying this relation are not known.

Objective: The objective of this study was to investigate the effects of maternal supplemental folic acid, with or without vitamin B-12, on adiposity, glucose homeostasis, and vascular health in adult male offspring mice.

Methods: Female C57BL/6J mice were fed a control diet (M-CON, 2 mg folic acid/kg, 50 μg vitamin B-12/kg) or a folic acid-supplemented diet with [10 mg folic acid/kg, 50 μg vitamin B-12/kg (SFA+B12)] or without [10 mg folic acid/kg, no vitamin B-12 (SFA-B12)] vitamin B-12 for 6 wk before mating and during pregnancy and lactation. The offspring were weaned onto a control diet (16% energy from fat) or a western diet (45% energy from fat) until 23 wk of age. The effects of maternal diet on adiposity, vascular function, and glucose tolerance were assessed in 6 groups of adult male offspring: control diet-fed M-CON, SFA+B12, and SFA-B12 and western diet-fed M-CON, SFA+B12, and SFA-B12.

Results: Control and western diet-fed SFA-B12 and SFA+B12 offspring had smaller visceral and subcutaneous adipose tissue than M-CON offspring (P < 0.05). Control SFA-B12 and SFA+B12 offspring had lower serum total adiponectin and vitamin B-12 concentrations and lower NADPH oxidase 2 expression in aorta compared with M-CON offspring (P < 0.05). These effects were not observed in western diet-fed offspring.

Conclusions: Folic acid supplementation of female mice before and during pregnancy and lactation, with or without dietary vitamin B-12, affects adult male offspring adiposity, vascular function, and one-carbon metabolism in those fed a control diet but not a western diet.
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http://dx.doi.org/10.3945/jn.115.227629DOI Listing
April 2015

High prevalence of suboptimal vitamin B12 status in young adult women of South Asian and European ethnicity.

Appl Physiol Nutr Metab 2015 Dec 21;40(12):1279-86. Epub 2015 Aug 21.

a Food Nutrition and Health, Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Suboptimal vitamin B12 (B12) status has been associated with an increased risk of congenital anomalies, preterm birth, and childhood insulin resistance. South Asians - Canada's largest minority group - and women of reproductive age are vulnerable to B12 deficiency. This study aimed to assess the prevalence of and factors associated with B12 deficiency and suboptimal B12 status in a convenience sample of young adult women of South Asian and European descent in Metro Vancouver. We measured serum B12, holotranscobalamin, plasma methylmalonic acid, red blood cell and plasma folate, and hematologic parameters in 206 nonpregnant, healthy women aged 19-35 years. Categorization for B12 status adhered to serum B12 cutoffs for deficiency (<148 pmol/L) and suboptimal B12 status (148-220 pmol/L). We collected demographic, lifestyle, and dietary intake data and conducted genotyping for common genetic variants linked to B-vitamin metabolism. The prevalence of deficiency and suboptimal B12 status were 14% and 20%, respectively. Serum vitamin B12 concentrations were negatively associated with oral contraceptive use and first-generation immigrant status, and positively with dietary B12 intake and B12 supplement use. The prevalence of B12 inadequacy in this sample of highly educated women is higher than in the general Canadian population. In light of maternal and fetal health risks associated with B12 inadequacy in early-pregnancy, practitioners should consider monitoring B12 status before and during early pregnancy, especially in immigrants and women with low dietary B12 intakes including non-users of vitamin supplements.
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http://dx.doi.org/10.1139/apnm-2015-0200DOI Listing
December 2015

Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain.

Am J Physiol Regul Integr Comp Physiol 2015 Sep 15;309(5):R613-22. Epub 2015 Jul 15.

Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Child and Family Research Institute, Vancouver, British Columbia, Canada

Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.
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http://dx.doi.org/10.1152/ajpregu.00075.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591382PMC
September 2015
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