Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.

Thiamin (Vitamin B1) - A scoping review for Nordic Nutrition Recommendations 2023.

Only a few studies have explored relationships between thiamine intake and function, and a few studies have examined the effects of supplements on various clinical or biochemical outcomes. None of these studies, however, makes a useful contribution to understanding requirements in healthy populations. The requirement of thiamine relates to energy and carbohydrate intake. Clinical signs of deficiency have been observed at intakes below 0.5 mg/day, which corresponds to 0.05 mg/MJ. In other studies, thiamine excretion in the urine and normalisation of enzyme activity were normalised at intakes of 0.07-0.08 mg/MJ. The lower limit of intake thus estimates at 0.05 mg/MJ. It has not been possible to set a safe upper intake level for thiamine due to a lack of data. Studies on pregnant and lactating women indicate a higher requirement as assessed by biochemical parameters. A few studies indicate that thiamine utilisation is impaired among elderly subjects.

The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial.

BACKGROUND: Vitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. OBJECTIVES: The study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. METHODS: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 µg (2-3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. RESULTS: LTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. CONCLUSIONS: Providing daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842.

Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study.

BACKGROUND: Vitamin B12 and folate are essential micronutrients important for normal infant growth and development. OBJECTIVES: The aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status. METHODS: Pregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo. RESULTS: At gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 µmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 µmol/L or 3 combined indicator of vitamin B12 (cB12) < -0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 µmol/L, 59% and 66% had MMA concentrations >0.26 µmol/L, and 47% and 60% had cB12 > -0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants' cobalamin and t-Hcy concentrations. CONCLUSIONS: Subclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences. This trial was registered at clinicaltrials.gov as NCT02610959.

Inadequate Iodine Intake in Mothers of Young Children in Innlandet County, Norway.

Background: Iodine has an essential role in child growth and brain development. Thus, sufficient iodine intake is particularly important in women of childbearing age and lactating women. Objectives: This cross-sectional study aimed to describe iodine intake in a large random sample of mothers of young children (aged ≤2 y) living in Innlandet County, Norway. Methods: From November 2020 to October 2021, 355 mother-child pairs were recruited from public health care centers. Dietary data were obtained using two 24-h dietary recalls (24-HRs) per woman and an electronic FFQ. The Multiple Source Method was used to estimate the usual iodine intake from the 24-HR assessment. Results: Based on the 24-HRs, the median (P25, P75) usual iodine intake from food was 117 µg/d (88, 153) in nonlactating women and 129 µg/d (95, 176) in lactating women. The median (P25, P75) total usual iodine intake (from food combined with supplements) was 141 µg/d (97, 185) in nonlactating women and 153 µg/d (107, 227) in lactating women. Based on the 24-HRs, 62% of the women had a total iodine intake below the recommendations (150 µg/d in nonlactating women and 200 µg/d in lactating women), and 23% of them had an iodine intake below the average requirement (100 µg/d). The reported use of iodine-containing supplements was 21.4% in nonlactating women and 28.9% in lactating women. In regular users of iodine-containing supplements (n = 63), supplements contributed to an average of 172 µg/d of iodine. Among regular iodine supplement users, 81% reached the recommendations compared with 26% of nonsupplement users (n = 237). The iodine intake estimated by FFQ was substantially higher than that estimated by 24-HRs. Conclusions: Maternal iodine intake in Innlandet County was inadequate. This study confirms the need for action to improve iodine intake in Norway, particularly among women of childbearing age.

The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment. METHODS: In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 µg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666. FINDINGS: 800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0·57 (SD 1·03) in the B12 group and -0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group. INTERPRETATION: Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy. FUNDING: Research Council of Norway.

Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial.

INTRODUCTION: Vitamin B12 (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B12 status and the status of other micronutrients in Norwegian infants, and (2) in a randomised controlled trial (RCT), investigate the effect of vitamin B12 supplementation on neurodevelopment in infants with subclinical vitamin B12 deficiency. METHODS AND ANALYSIS: Infant blood samples, collected at public healthcare clinics, are analysed for plasma cobalamin levels. Infants with plasma cobalamin <148 pmol/L are immediately treated with hydroxocobalamin and excluded from the RCT. Remaining infants (cobalamin ≥148 pmol/L) are randomly assigned (in a 1:1 ratio) to either a screening or a control group. In the screening group, baseline samples are immediately analysed for total homocysteine (tHcy), while in the control group, the baseline samples will be analysed after 12 months. Screening group infants with plasma tHcy >6.5 µmol/L, are given an intramuscular injection of hydroxocobalamin (400 µg). The primary outcomes are cognitive, language and motor development assessed using the Bayley Scales of Infant and Toddler Development at 12 months of age. ETHICS AND DISSEMINATION: The study has been approved by the Regional Committee for Medical and Health Research Ethics (ref: 186505). Investigators who meet the Vancouver requirements will be eligible for authorship and be responsible for dissemination of study findings. Results will extend current knowledge on consequences of subclinical vitamin B12 deficiency during infancy and may inform future infant feeding recommendations. TRIAL REGISTRATION NUMBER: NCT05005897.

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6-7 Years: A Follow-Up of a Randomized Controlled Trial.

BACKGROUND: Deficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. OBJECTIVES: We investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6-7 y. METHODS: This is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6-30-mo-old children. The supplement contained 1.8 µg of vitamin B12, 150 µg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016-November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). RESULTS: At baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 µmol/L (95% CI: 0.09; 2.30 µmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin-adiponectin ratio in subgroups based on their nutritional status. CONCLUSIONS: Supplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations. The original trial was registered at www. CLINICALTRIALS: gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.

The effect of infant vitamin B12 supplementation on neurodevelopment: a follow-up of a randomised placebo-controlled trial in Nepal.

The most critical period for brain development is before a child's second birthday. Standardised tests measuring neurodevelopment are more reliable when administered after this period. Severe vitamin B12 deficiency affects brain development and function. In a randomised, double-blind, placebo-controlled trial in 600 Nepalese infants (6-11 months at enrolment), we found no effect of 2 µg vitamin B12 daily for a year on neurodevelopment. The primary objective of the current study was to measure the effect of the intervention on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) full scale intelligence quotient (FSIQ). We measured the effect on the Bayley Scales of Infant and Toddler Development 3rd edition at age 30-35 months (n 555). At age 42-47 months (n 533), we used the WPPSI-IV and subtests from the Neuropsychological Assessment, 2nd edition (NEPSY-II). We also used the FSIQ to estimate subgroup specific effects. The mean (sd) WPPSI-IV FSIQ in the vitamin B12 group was 84·4 (8·4) and 85·0 (8·6) in the placebo group (mean difference -0·5 (95 % CI -1·97, 0·94), P = 0·48). There were no effect of the vitamin B12 on any of the other neurodevelopmental outcomes and no beneficial effect in any of the subgroups. In conclusion, providing 2 µg of vitamin B12 for a year in infants at risk of vitamin B12 deficiency does not improve preschool cognitive function.

The association between household biomass fuel use and leukocyte telomere length among toddlers in Bhaktapur, Nepal.

BACKGROUND: Biomass fuels are still in use for cooking by many households in resource poor countries such as Nepal and is a major source of household air pollution (HAP). Chronic exposure to HAP has been shown to be associated with shorter telomere length in adults. OBJECTIVES: To measure the association between exposure related to household biomass fuel in infancy and leukocyte telomere length (LTL) at 18-23 months of age among 497 children from Bhaktapur, Nepal. METHODS: In a prospective cohort study design, we have collected information on household cooking fuel use and several clinical, anthropometric, demographic, and socioeconomic variables. We estimated the association between biomass fuel use and the relative LTL in multiple linear regression models. RESULTS: Most of the families (78%) reported liquified petroleum gas (LPG) as the primary cooking fuel, and 18.7% used biomass. The mean relative (SD) LTL was 1.03 (0.19). Children living in households using biomass fuel had on average 0.09 (95% CI: 0.05 to 0.13) units shorter LTL than children in households with no biomass fuel use. The observed association was unaltered after adjusting for relevant confounders. The association between LTL and biomass use was strongest among children from households with ≤2 rooms and without separate kitchen. SIGNIFICANCE: Exposure to biomass fuel use in early life might have consequences for longevity, and risk of chronic illnesses reflected in shortening of the telomeres. Our findings support the ongoing effort to reduce exposure to biomass fuel in low-resource settings. IMPACT STATEMENTS: Biomass for cooking is a leading source of household air pollution in low and middle-income countries, contributing to many chronic diseases and premature deaths. Chronic exposure to biomass fuel through oxidative stress and inflammation has been associated with a shortening of the telomeres, a "biological marker" of longevity. This prospective cohort study describes the association between household biomass fuel use and leukocyte telomere length among 497 toddlers. Leukocyte telomere length was significantly shorter among children living in households with biomass fuel than in children from homes where mainly LPG was used for cooking. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT02272842, registered October 21, 2014, Universal Trial Number: U1111-1161-5187 (September 8, 2014).

Vitamin B12 and/or folic acid supplementation on linear growth; a 6 years follow-up study of a randomised controlled trial in early childhood in North India.

Folate and vitamin B12 are essential for growth. Our objective was to estimate their long-term effects on linear growth in North Indian children. This is a follow-up study of a factorial designed, double-blind, randomized placebo-controlled trial in 1,000 young children. Starting at 6-30 months of age, we gave folic acid (∼2 RDAs), vitamin B12 (∼2 RDAs), both vitamins, or a placebo daily for six months. Six years after the end of supplementation, we measured height in 791 children. We used the plasma concentrations of cobalamin, folate, and total homocysteine to estimate vitamin status. The effect of the interventions, the association between height-for-age z-scores (HAZ) and baseline vitamin status, and the interactions between supplementation and baseline status were estimated in multiple regression models. Mean (SD) age at follow-up was 7.4 (0.7) years (range 6 to 9 years). There was a small, non-significant effect of vitamin B12 on linear growth and no effect of folic acid. We observed a subgroup-effect of vitamin B12 supplementation in those with plasma cobalamin concentration < 200 pmol/L (P interaction = 0.01). The effect of vitamin B12 supplementation in this group was 0.34 HAZ (95% CI: 0.11-0.58). We found an association between cobalamin status and HAZ in children not given vitamin B12 (P interaction = 0.001). In this group, each doubling of the cobalamin concentration was associated with 0.26 (95% CI: 0.15 to 0.38) higher HAZ. Suboptimal B12 status in early childhood seemingly limits linear growth in North Indian Children.

Distribution and Determinants of Serum Zinc, Copper, and Selenium Levels among Children under Five Years from Popokabaka, Democratic Republic of Congo: A Cross-Sectional Study.

Information about essential trace elements among children in many African countries, including the Democratic Republic of Congo (DRC), is limited. We aimed to measure the distribution and determinants of serum zinc (Zn), copper (Cu), and selenium (Se) concentrations in a representative sample of children under five years old. We conducted a community-based cross-sectional study in Popokabaka, DRC. Blood samples were drawn from 412 children. The serum concentrations of minerals were measured using inductively coupled plasma−mass spectrometry. The median concentrations (P25−P75) of Zn, Cu, and Se were 61.9 µg/dL (52.8−70.2), 145.5 (120.0−167.0) µg/dL and 5.3 (4.3−6.3) µg/dL. The CRP-adjusted prevalence of serum Se deficiency was 84.1% (95% confidence interval [CI] 81.4−87.0) and of Zn deficiency was 64.6% (95% CI 59.8−69.1%). Only a few children were Cu deficient [1.5% (0.6−3.2)]. Evidence of inflammation (C-reactive protein, >5 mg/L) was associated with a lower Se concentration and higher Cu concentration. Furthermore, serum Se concentration was positively associated with linear growth. The average Cu/Zn molar ratio (2:1) was twice that recommended. Children in western Popokabaka had higher Zn and Se levels than their eastern neighbors. Zinc and selenium deficiencies are common among children in Popokabaka and require attention and prioritization.

The effect of vitamin B12-supplementation on actigraphy measured sleep pattern; a randomized control trial.

BACKGROUND: Vitamin B12 deficiency is common worldwide and has been associated with poor sleep. The effect of vitamin B12 supplementation on sleep in infants is not known. AIMS: To measure the effect of daily supplementation of vitamin B12 for one year on sleep in infants at risk of deficiency. METHODS: This was an individually randomized double-blind placebo-controlled trial in 600 infants in low-to middle-income neighborhoods in Bhaktapur, Nepal of daily supplementation of vitamin B12 for one year. Infants were included if they were 6-11 month year-old and with a length-for-age less than one z-score. Sleep was a predefined, secondary outcome, and was measured by actigraphy including sleep duration at night and total sleep duration (day and night), sleep onset latency (SOL), and wake after sleep onset (WASO). The effect of vitamin B12 on sleep was additionally assessed in predefined subgroups defined by stunting, underweight, vitamin B12 status, low birthweight, anemia and exclusive breastfeeding for 3 months. RESULTS: There was no effect of vitamin B12 supplementation on sleep duration at night, total sleep duration, or WASO. There was a small significant negative effect for SOL. None of the included subgroup analyses revealed effect modification on any of the sleep outcomes. CONCLUSION: Overall, vitamin B12 supplementation did not have an effect on sleep in infants or for high-risk subgroups, with the exception of a small negative effect for SOL. The present study does not support vitamin B12 supplementation to improve sleep in infants. TRIAL REGISTRATION: clinicaltrials.gov: NCT02272842. UNIVERSAL TRIAL NUMBER: U1111-1161-5187.

Impact of the COVID-19 pandemic on daily life and worry among mothers in Bhaktapur, Nepal.

The COVID-19 pandemic has affected many aspects of daily life worldwide, but the impact may be higher for impoverished populations. The main aim of this study is to describe the impact of the COVID-19 pandemic on different aspects of daily life in mothers in Nepal. We included 493 mothers of children aged 54-71 months participating in a randomized controlled trial on vitamin B12 supplementation. Mothers answered questions regarding the exposure and impact of the pandemic on their daily lives, and pandemic-related worries and sleep problems. We examined the extent to which worry, and sleep problems differed between mothers according to their exposure to COVID-19, socioeconomic status, and previous symptoms of depression. The mean age (SD) of the mothers was 32.3 (4.6) years and 54% had education below the secondary level. Of the mothers, 5.4% had either been exposed to someone who had tested positive or who had a family member with COVID-19. One-third of the participants responded that the pandemic had affected their economic situation, employment, and family life to a great deal. Both mothers and fathers with educational levels above 10 years or households with higher socioeconomic status had significantly higher average worry scores (maternal p = 0.020 and paternal p = 0.005). Mothers with a history of symptoms of depression had significantly more worry-related sleep problems during the pandemic (p = 0.020) than those without a history of depressive symptoms. Our study underlines the negative impact of the COVID-19 pandemic on diverse aspects of everyday life of mothers in Nepal.

Iodine Nutrition and Iodine Supplement Initiation in Association with Thyroid Function in Mildly-to-Moderately Iodine-Deficient Pregnant and Postpartum Women.

BACKGROUND: Whereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established. OBJECTIVES: We aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women. METHODS: In this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models. RESULTS: The median UIC at GW18 was 94 µg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (ß; 95% CI) per 100 µg/g was negatively associated with fT3 (-0.191; -0.331, -0.051) and fT4 (-0.756; -1.372, -0.141) concentrations. Iodine intake (ß; 95% CI) per 100 µg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (-0.084; -0.0141, -0.027) and fT4 (-0.390; -0.599, -0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations. CONCLUSIONS: Lower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy.This trial was registered at clinicaltrials.gov as NCT02610959.

Gestational Age, Birth Weight, and Neurocognitive Development in Adolescents in Tanzania.

OBJECTIVES: To investigate the association between gestational age, birthweight, and birthweight adjusted for gestational age, with domains of neurocognitive development and behavioral problems in adolescents in Tanzania. STUDY DESIGN: Data from a long-term follow-up of adolescents aged 11-15 years born to women previously enrolled in a randomized controlled trial of prenatal multiple micronutrient supplementation in Dar es Salaam, Tanzania, were used. A battery of neurodevelopmental tests were administered to measure adolescent general intelligence, executive function, and behavioral problems. The INTERGROWTH-21st newborn anthropometric standards were used to derive birthweight for gestational age z-scores. We assessed the shape of relationships using restricted cubic splines and estimated the associations of gestational age, birthweight, and birthweight for gestational age z-score with adolescent development using multivariable linear regressions. RESULTS: Among adolescents studied (n = 421), higher gestational age (per week), birthweight (per 100 grams), and birthweight for gestational age z-score (per SD) were linearly associated with higher intelligence score (adjusted standardized mean difference, 0.05 SD [95% CI, 0.01-0.09], 0.04 SD [95% CI, 0.02-0.06], and 0.09 SD [95% CI, 0.01-0.17], respectively). Birthweight and birthweight for gestational age z-score, but not gestational age, were also associated with improved executive function. Low birthweight (<2500 g) was associated with lower intelligence and executive function scores. Associations between birthweight and executive function were stronger among adolescents born to women with higher education. CONCLUSIONS: The duration of gestation and birthweight were positively associated with adolescent neurodevelopment in Tanzania. These findings suggest that interventions to improve birth outcomes may also benefit adolescent cognitive function.

Vitamin D3 supplementation does not enhance the effects of resistance training in older adults.

BACKGROUND: Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those with chronic diseases (e.g. chronic obstructive pulmonary disease, COPD) and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. METHODS: Ninety-five male and female participants (healthy, n = 71; COPD, n = 24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61°N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (two weeks with 10 000 IU/day, followed by 2000 IU/day), followed by 13 weeks of combined supplementation (2000 IU/day) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (nvariables  = 7), endurance performance (n = 6), and muscle mass (n = 3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. RESULTS: Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%), and endurance performance (one-legged, 23% ± 15%; whole-body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, -6% ± 21%; [LDL]serum , -4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, -3% points), myonuclei per fibre (30% ± 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. 312 differentially expressed genes). Vitamin D3 supplementation did not affect training-associated changes for any of the main outcome domains, despite robust increases in [25(OH)D]serum (∆49% vs. placebo). No conditional effects were observed for COPD vs. healthy or pre-RCT [25(OH)D]serum . In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue and strength gains in participants with high fat mass, which advocates further study. CONCLUSIONS: Vitamin D3 supplementation did not affect muscular responses to resistance training in older adults with or without COPD.

Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial.

BACKGROUND: Vitamin B12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. METHODS AND FINDINGS: This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 µg of vitamin B12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): -0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: -1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: -0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B12 supplementation might not have covered a critical window for infant growth or brain development. CONCLUSIONS: In this study, we observed that vitamin B12 supplementation in young children at risk of vitamin B12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B12 supplementation in marginalized infants from low-income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information).

Prevalence of Underweight, Overweight, and Obesity in Adults in Bhaktapur, Nepal in 2015-2017.

Introduction: There is an increase in the double burden of malnutrition globally, with a particular rise documented in Asia. In Nepal, undernutrition has been prevalent for decades. Today, however, the incidence of overweight and obesity (OWOB) in the country has increased substantially. There is a need to conduct local studies reporting on the concurrent burden of both underweight and OWOB across adult populations. This study addresses this need by describing the distribution of body mass index (BMI) in a defined population of adults living in the peri-urban community of Bhaktapur, Nepal. Material and methods: For this cross-sectional analysis, we used data that were available from 600 women and 445 men whose children were enrolled in an individually randomized, double-blind, placebo-controlled trial assessing the effect of daily vitamin B12 supplementation. Upon enrolment of their 6-11-month old children, mothers and fathers were interviewed about their socio-demographic details. In addition, their weight and height were measured by trained field workers. Each parent's BMI was calculated as the ratio of body weight (in kg) and height squared (in m), expressed as kg/m2, and categorized according to the WHO recommendation. We used linear and multinomial logistic regression models to assess associations between the BMI of the mothers and fathers, and their baseline characteristics. Results: The mean BMI was 23.7 kg/m2 for both the mothers and fathers with a standard deviation (SD) of 3.6 and 3.7, respectively. The proportion categorized as underweight, overweight, and obese was also similar in the two groups with around 5% being underweight, 30% being overweight and 5% being obese. Age was positively associated with BMI in both groups. Those categorized as daily wage earner had a lower mean BMI than those in other occupational groups. Conclusion: Our results contribute to documenting the burden of both under- and overnutrition in a selected group of young adults living in a peri-urban community in Nepal. As Nepal is undergoing an improvement in its economic situation, as well as a nutrition transition, it is important to provide sufficient information to enable timely action, and evidence-based decision-making to prevent a further increase in Nepal's growing double burden of malnutrition.

Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19.

OBJECTIVES: The novel coronavirus infection (COVID-19) conveys a serious threat globally to health and economy because of a lack of vaccines and specific treatments. A common factor for conditions that predispose for serious progress is a low-grade inflammation, e.g., as seen in metabolic syndrome, diabetes, and heart failure, to which micronutrient deficiencies may contribute. The aim of the present article was to explore the usefulness of early micronutrient intervention, with focus on zinc, selenium, and vitamin D, to relieve escalation of COVID-19. METHODS: We conducted an online search for articles published in the period 2010-2020 on zinc, selenium, and vitamin D, and corona and related virus infections. RESULTS: There were a few studies providing direct evidence on associations between zinc, selenium, and vitamin D, and COVID-19. Adequate supply of zinc, selenium, and vitamin D is essential for resistance to other viral infections, immune function, and reduced inflammation. Hence, it is suggested that nutrition intervention securing an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate the course of COVID-19. CONCLUSION: We recommended initiation of adequate supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority as regards this nutritive adjuvant therapy, which should be started prior to administration of specific and supportive medical measures.