Vitamin B12, folate, and cognition in 6-to 9-year-olds: a randomized controlled trial

BACKGROUND AND OBJECTIVES: Vitamin B12 and folate are important for normal brain development. Our objective for this study was to measure the effects of 6-month supplementation of vitamin B12 and/or folic acid in early childhood on cognition when the children were 6 to 9 years old. METHODS: The study is a follow-up of a factorial randomized, double-blind, placebo-controlled trial in 1000 North Indian children. Children 6 to 30 months of age were randomly assigned to receive a placebo or 1.8 µg of vitamin B12, 150 mg of folic acid, or both daily for 6 months. After 6 years, we re-enrolled 791 of these children for cognitive assessments. We compared the scores of the main outcomes (the Wechsler Intelligence Scale for Children, Fourth Edition [India], the Crichton Verbal Scale, and subtests of the NEPSY-II) between the study groups. We also measured the associations between markers of the B vitamins (plasma cobalamin, folate, and total homocysteine concentrations) in early childhood and the cognitive outcomes. RESULTS: There were no differences between the intervention groups and the placebo group on the cognitive outcomes. Plasma cobalamin, folate, and total homocysteine concentrations in early childhood were associated with the cognitive outcomes at follow-up in the unadjusted models. These associations disappeared in models adjusted for relevant confounders. CONCLUSIONS: Our findings, from both an observational and a randomized design suggest that vitamin B12 and folate in children 6 to 36 months have limited public health relevance for long-term cognition.Thrasher Research Fund (grant 02827) and the Research Council of Norway (grants 172226 and 234495) provided financial support for the original and the follow-up study.AcceptedVersio

Milk-cereal mix supplementation during infancy and impact on neurodevelopmental outcomes at 12 and 24 months of age: A randomized controlled trial in India

Inadequate protein intake and lack of micronutrients may affect neurodevelopment in infants. This randomised controlled trial was conducted to measure the effect of two milk–cereal mixes with modest and high amounts of protein and enriched with multiple micronutrients, given between 6 and 12 months, on cognitive, language, motor and behavioural scores at 12 and 24 months of age, compared with no-supplementation. The two supplements were also compared with each other. The study was conducted in urban Delhi, India, and the infants were randomised in a 1:1:1 ratio to the three study groups. At 12 and 24 months of age, 1134 and 1214 children were available, respectively. At 12 months of age, compared with no-supplement group, an increase in the motor scores (mean difference, MD 1·52, 95 % CI: 0·28, 2·75) and a decrease in the infant temperament scores (MD − 2·76, 95 % CI: −4·23, −1·29) in the modest-protein group was observed. Those in the high-protein group had lower socio-emotional scores (MD − 1·40, 95 % CI: −2·43, −0·37) and higher scores on Infant Temperament Scale (MD 2·05, 95 % CI: 0·62, 3·48) when compared with modest-protein group. At 24 months, no significant differences in any of the neurodevelopment scores between the three study groups was found. In conclusion, supplementation with modest amount of protein and multiple micronutrients may lead to short-term small improvements in motor function and infant temperament. There appears no advantage of supplementing with high protein, rather negative effects on infant behaviour were observedpublishedVersio

Enteral Calcium or Phosphorus Supplementation in Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis

OBJECTIVES To assess effects of calcium or phosphorous supplementation compared with no supplementation in human milk-fed preterm or low birth weight infants. METHODS Data sources include Cochrane Central Register of Controlled Trials, Medline and Embase. We included Randomized controlled trials (RCTs) and non-randomized trials (quasi-randomized). RESULTS Three studies (4 reports; 162 infants) were included. At latest follow-up (38 weeks), there was reduction in osteopenia (3 studies, 159 participants, relative risk 0.68, 95% confidence interval [CI] 0.46–0.99). At latest follow-up (6 weeks), there was no effect on weight (1 study, 40 participants, mean difference [MD] 138.50 g, 95% CI −82.16 to 359.16); length (1 study, 40 participants, MD 0.77 cm, 95% CI −0.93 to 2.47); and head circumference (1 study, 40 participants, MD 0.33 cm, 95% CI −0.30 to 0.96). At latest follow-up, there was no effect on alkaline phosphatase (55 weeks) (2 studies, 122 participants, MD −126.11 IU/L, 95% CI −298.5 to 46.27, I2 = 73.4%); serum calcium (6 weeks) (1 study, 40 participants, MD 0.54 mg/dL, 95% CI −0.19 to 1.27); and serum phosphorus (6 weeks) (1 study, 40 participants, MD 0.07 mg/dL, 95% CI −0.22 to 0.36). The certainty of evidence ranged from very low to low. No studies reported on mortality and neurodevelopment outcomes. CONCLUSIONS The evidence is insufficient to determine whether enteral supplementation with calcium or phosphorus for preterm or low birth weight infants who are fed mother's own milk or donor human milk is associated with benefit or harm.publishedVersio

Enteral Zinc Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Evidence on the effect of zinc supplementation on health outcomes in preterm or low birth weight (LBW) infants is unclear. We estimated the effect of enteral zinc versus no zinc supplementation in human milk fed preterm or LBW infants on mortality, growth, morbidities, and neurodevelopment. METHODS Data sources include PubMed, Cochrane Central and Embase databases through March 24, 2021. Study selection was randomized or quazi-experimental trials. Two reviewers independently screened, extracted data, and assessed quality. We reported pooled relative risks (RR) for categorical outcomes, and mean differences (MD) for continuous outcomes. RESULTS Fourteen trials with 9940 preterm or LBW infants were included. Moderate to low certainty evidence showed that enteral zinc supplementation had little or no effect on mortality (risk ratio 0.73, 95% confidence interval [CI] 0.46 to 1.16), but increased weight (MD 378.57, 95% CI 275.26 to 481.88), length (MD 2.92, 95% CI 1.53 to 4.31), head growth (MD 0.56, 95% CI 0.23 to 0.90), and decreased diarrhea (RR 0.81; 95% CI 0.68 to 0.97). There was no effect on acute respiratory infections, bacterial sepsis, and psychomotor development scores. The effect of zinc supplementation on mental development scores is inconclusive. There was no evidence of serious adverse events. Eight trials had some concerns or high risk of bias, small-sized studies, and high heterogeneity between trials led to moderate to very low certainty of evidence. CONCLUSIONS Zinc supplementation in preterm or LBW infants have benefits on growth and diarrhea prevention. Further research is needed to generate better quality evidence.publishedVersio

Cameron-Liebler sets of k-spaces in PG(n,q)

Cameron-Liebler sets of k-spaces were introduced recently by Y. Filmus and F. Ihringer. We list several equivalent definitions for these Cameron-Liebler sets, by making a generalization of known results about Cameron-Liebler line sets in PG(n, q) and Cameron-Liebler sets of k-spaces in PG(2k + 1, q). We also present a classification result

Enteral Vitamin D Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Many preterm and low birth weight (LBW) infants have low vitamin D stores. The objective of this study was to assess effects of enteral vitamin D supplementation compared with no vitamin D supplementation in human milk fed preterm or LBW infants. METHODS Data sources include Cochrane Central Register of Controlled Trials, Medline, and Embase from inception to March 16, 2021. The study selection included randomized trials. Data were extracted and pooled with fixed and random-effects models. RESULTS We found 3 trials (2479 participants) that compared vitamin D to no vitamin D. At 6 months, there was increase in weight-for-age z-scores (mean difference 0.12, 95% confidence interval [CI] 0.01 to 0.22, 1 trial, 1273 participants), height-for-age z-scores (mean difference 0.12, 95% CI 0.02 to 0.21, 1 trial, 1258 participants); at 3 months there was decrease in vitamin D deficiency (risk ratio 0.58, 95% CI 0.49 to 0.68, I2=58%, 2 trials, 504 participants) in vitamin D supplementation groups. However, there was little or no effect on mortality, any serious morbidity, hospitalization, head circumference, growth to 6 years and neurodevelopment. The certainty of evidence ranged from very low to moderate. Fourteen trials (1969 participants) assessed dose and reported no effect on mortality, morbidity, growth, or neurodevelopment, except on parathyroid hormone and vitamin D status. No studies assessed timing. Limitations include heterogeneity and small sample size in included studies. CONCLUSIONS Enteral vitamin D supplementation improves growth and vitamin D status in preterm and LBW infants.publishedVersio

Utilisation, equity and determinants of full antenatal care in India: analysis from the National Family Health Survey 4

Objectives: We examined the utilisation, equity and determinants of full antenatal care (ANC), defined as 4 or more antenatal visits, at least one tetanus toxoid (TT) injection and consumption of iron folic acid (IFA) for a minimum of 100 days, in India. Methods: We analysed a sample of 190,898 women from India’s National Family Health Survey 4. Concentration curves and concentration index were used to assess equity in full ANC utilisation. Multivariable logistic regression model was used to examine the factors associated with full ANC utilisation. Results: In India, 21% of pregnant women utilised full ANC, ranging from 2.3–65.9% across states. Overall, 51.6% had 4 or more ANC visits, 30.8% consumed IFA for atleast 100 days, and 91.1% had one or more doses of tetanus toxoid. Full ANC utilisation was inequitable across place of residence, caste and maternal education. Registration of pregnancy, utilisation of government’s Integrated Child Development Services (ICDS) and health insurance coverage were associated with higher odds of full ANC utilisation. Lower maternal education, lower wealth quintile(s), lack of father’s participation during antenatal visits, higher birth order, teenage and unintended pregnancy were associated with lower odds of full ANC utilisation. Conclusions: Full ANC utilisation in India was inadequate and inequitable. Although half of the women did not receive the minimum recommended ANC visits, the utilisation of TT immunisation was almost universal. The positive association of full ANC with ICDS utilisation and child’s father involvement may be leveraged for increasing the uptake of full ANC. Strategies to address the socio-demographic factors associated with low and inequitable utilisation of full ANC are imperative for strengthening India’s maternal health program.publishedVersio

Enteral Iron Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Iron is needed for growth and development of infants globally, but preterm and low birth weight (LBW) infants are at risk for severe iron deficiencies. To assess the effect of enteral iron supplementation on mortality, morbidity, growth, and neurodevelopment outcomes in preterm or LBW infants fed human milk. Secondary objectives were to assess the effect on biomarkers and dose and timing. METHODS Data sources include PubMed, Embase and Cochrane Library databases to March 16, 2021. Study Selection includes controlled or quasi experimental study designs. Two reviewers independently extracted data. RESULTS Eight trials (eleven reports; 1093 participants, 7 countries) were included. No trials reported mortality. At latest follow-up, there was little effect on infection (very low certainty evidence, 4 studies, 401 participants, relative risk [RR] 0.98, 95% confidence interval [95% CI] 0.56 to 1.73, I2 = 0.00%) and necrotising enterocolitis (3 studies, 375 participants, RR 1.47, 95% CI 0.68 to 3.20, I2 = 0.00%). There was an increase in linear growth (length) (moderate certainty evidence, 3 studies, 384 participants, mean difference 0.69 cm, 95% CI 0.01 to 1.37, I2 = 0%) but little effect on weight, head circumference, or cognitive development. There was an improvement in anemia (moderate certainty evidence, 2 studies, 381 participants, RR 0.25, 95% CI 0.10 to 0.62, I2 = 0.00%) but no effect on serum ferritin. Limitations include heterogeneity in the included studies. CONCLUSIONS There are important benefits for human milk-fed preterm and LBW infants from enteral iron supplementation. However, more randomized control trials are required to improve the certainty of evidence.publishedVersio

Enteral Multiple Micronutrient Supplementation in Preterm and Low Birth Weight Infants: A Systematic Review and Meta-analysis

OBJECTIVES To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.publishedVersio

Long Term Two-Phase Flow Analysis of the Deep Low Permeability Rock at the Bruce DGR Site

Abnormal pressures have been measured in the deep boreholes at the Bruce site, southern Ontario, where a deep geologic repository for low and intermediate level radioactive waste disposal has been proposed. The pressure regime in the stratigraphic units exhibits either higher than hydrostatic pressure (over-pressured) or lower than hydrostatic pressure (under-pressured) are considered to be abnormal. At the Bruce site, the Ordovician sediments are under-pressured while the underlying Cambrian sandstone and the overlying Guelph carbonate are over-pressured. Hypotheses have been documented in literature to explain the phenomenon of abnormal pressures. These hypotheses include osmosis, glacial loading and deglaciation unloading, exhumation of overlying sediments, crustal flexure and the presence of an immiscible gas phase. Previous work on the Bruce site has shown that the under-pressures in the Ordovician limestone and shales could not be explained by glaciation and deglaciation or by saturated analyses. The presence of a gas phase in the Ordovician formations has been determined to be a reasonable cause of the under-pressure developed in the Ordovician shales and limestones at the Bruce site. Support for the presence of a gas phase includes solution concentrations of methane, concentrations of environmental isotopes related to methane and estimates of water and gas saturations from laboratory core analyses. The primary contribution of this thesis is the sensitivity analyses performed on the hydrogeologic parameters with respect to a one dimensional two-phase flow model. First, a one dimensional two-phase air and water flow model was adopted and reconstructed to simulate the long-term evolution of the groundwater regimes at the DGR site. Then the hydrogeologic parameters which impact the presence of under-pressure in the groundwater are investigated. Data required to quantify the properties of geologic media and groundwater are adopted directly from borehole testing and laboratory testing results. The permeable boundaries of the domain are assumed to be water saturated and pressure specified (using hydrostatic conditions in the Guelph Formation and hydrostatic with 120 m over-pressure condition in the Cambrian and Precambrian). Isothermal conditions were assumed, thus constant water density and viscosity values are estimated for the average total dissolved solids (TDS) concentration of the modelled stratigraphic column. A constant diffusion coefficient (a diffusivity of $0.25\times10^{-8}$ m$^2$/s) of air in water is assumed with a saturation-dependent tortuosity. The air generation rate is assumed to simulate the gas phase generated in the Ordovician formations. The numerical simulation of up to 4 million years provides a means to explore the behaviour of gas phase dissipation due to partitioning into the water phase and diffusive transport in the solute phase. Results confirmed that the presence of a gas phase would result in the under-pressure in water