Intake of vitamin B12 in relation to vitamin B12 status in groups susceptible to deficiency: a systematic review.

Objective: To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0-18 years), young adults (18-35 years), pregnant or lactating women, older adults (≥65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund. Results: The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy - all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited - no conclusion for all included populations. Conclusion: Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted.

Supplementation with long chain n-3 fatty acids during pregnancy, lactation, or infancy in relation to risk of asthma and atopic disease during childhood: a systematic review and meta-analysis of randomized controlled clinical trials.

Objective: To assess whether supplementation with long chain n-3 fatty acids during pregnancy, lactation, or infancy reduces the risk of developing asthma or atopic disease during childhood. Methods: Searches were performed in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 2021-09-20, for randomized controlled trials (RCTs) that investigated the effect of supplemental long chain n-3 fatty acids during pregnancy, lactation, or infancy for the prevention of childhood asthma or allergy. Article selection, data extraction, and risk of bias assessment (Cochrane's Risk of Bias 2.0) were independently conducted by two assessors. The evidence was synthesized qualitatively according to the criteria of the World Cancer Research Fund and meta-analyzed. Results: A total of nine RCTs met inclusion criteria; six were conducted during pregnancy, two during infancy, and one during both pregnancy and infancy. Meta-analysis showed that long chain n-3 fatty acid supplementation during pregnancy significantly reduced the risk of asthma/wheeze in the child (RR 0.62 [95% confidence interval 0.34-0.91], P = 0.005, I 2 = 67.4%), but not other outcomes. Supplementation during lactation of infancy showed no effects on any outcome. The strength of evidence that long chain n-3 fatty acid supplementation during pregnancy reduces risk of asthma/wheeze in the offspring was considered limited - suggestive. No conclusion could be made for the effects of long chain n-3 fatty acid supplementation during pregnancy for other atopic diseases, or for supplementation during lactation or infancy for any outcome. Conclusion: The intake of long chain n-3 fatty acid supplements during pregnancy may reduce the risk of asthma and/or wheeze in the offspring, but the strength of evidence is low. There is inconclusive evidence for the effects of long chain n-3 fatty acid supplements during pregnancy for other outcomes, as well as for supplementation during lactation or infancy.

Quality of dietary fat and risk of Alzheimer's disease and dementia in adults aged ≥50 years: a systematic review.

Objective: To identify, critically appraise, and synthesize evidence on the effect of quality of dietary fat intake and different classes of fatty acids on the risk of Alzheimer's disease (AD) and dementia in adults aged ≥50 years. Methods: We searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until May 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Classes of fatty acids included were saturated fatty acids (SFAs), trans fatty acids (TFAs), monounsaturated fatty acids (MUFAs), poly-unsaturated fatty acids (PUFAs), and their subtypes and sources. Given between-study heterogeneity, we did not perform meta-analyses but narratively described findings from the studies. Results: From 4,491 identified records, five articles (based on four prospective cohort studies) met the inclusion criteria. Three studies had an overall serious risk of bias, while one study had a moderate risk. Overall, we found no robust association between intake of any fatty acids type and the development of AD and dementia. For example, for SFA and TFA, there was contradictory associations reported on AD: one study found that each unit increase in energy-adjusted intake of SFA (risk ratio [RR] 0.83, 95%CI 0.70-0.98) and TFA (RR 0.80, 95%CI 0.65-0.97) was associated with a decreased risk of AD, but not dementia. For PUFA, one study found that higher quintile intake of marine-based n-3 PUFA was associated with a decreased risk of AD. The intake of other fatty acids was not associated with the outcomes. The certainty of the overall evidence was inconclusive. Conclusion: We found no clear association between the intake of various classes of fatty acids and the risk of AD and dementia in adults. More well-designed prospective studies are required to clarify these findings.

Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis.

It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2  = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.

EAACI position paper: Influence of dietary fatty acids on asthma, food allergy, and atopic dermatitis.

The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid-associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis.

Vitamin D intake during the first 4 years and onset of asthma by age 5: A nested case-control study.

BACKGROUND: Early-life vitamin D intake has been linked to asthma risk in childhood, but the role of longitudinal vitamin D exposure has not been previously evaluated. We investigated the association between vitamin D intake during the first 4 years of life and asthma risk by age 5. METHODS: Within a Finnish population-based birth cohort, 182 incident asthma cases were matched to 728 controls on sex, genetic risk for type 1 diabetes, delivery hospital, and time of birth. Vitamin D intake was assessed by age-specific 3 day food records. Parents completed a validated version of the International Study of Asthma and Allergies in Childhood questionnaire at 5 years. RESULTS: At 3 months, supplements were the main source of vitamin D intake; intake from foods increased from 3 months on, mainly from fortified milk products. Vitamin D intake at each specific age was associated with an increased risk of any asthma, atopic, and non-atopic asthma, but only intake at 1 and 2 years was statistically significantly associated with asthma. Longitudinal vitamin D intake was associated with an increased risk of asthma (OR 1.24; 95%CI 1.00-1.53). CONCLUSIONS: Increased vitamin D intake in childhood, particularly intake at 1 and 2 years of age, may increase risk of childhood asthma. This might reflect a true effect or residual confounding by lifestyle or environmental factors. Repeated assessment of vitamin D intake allowed evaluation of the longitudinal and age-dependent impact of vitamin D on the risk of asthma. Further longitudinal studies are required to confirm or question these findings.

Periconception endogenous and exogenous maternal sex steroid hormones and risk of asthma and allergy in offspring: protocol for a systematic review and meta-analysis.

INTRODUCTION: Pregnancy is associated with several hormonal changes which influence the developing fetus. Variations in maternal endogenous hormones and prepregnancy use of hormonal preparations have been linked to asthma and allergy in the offspring, but findings are inconsistent. We plan to undertake a systematic review to synthesise the evidence on the association between endogenous and exogenous maternal sex hormones and the risk of asthma and allergy in the offspring. METHODS AND ANALYSIS: We will search Medline, Embase, Cochrane Library, Institute of Scientific Information Web of Science, Cumulative Index of Nursing and Allied Health, Scopus, Google Scholar, Allied and Complementary Medicine Database, Global Health, Psychological Information (PsycINFO), Centre for Agriculture and Bioscience (CAB) International and WHO Global Health Library from inception until 2016 to identify relevant studies on the topic. Additional studies will be identified by searching databases of proceedings of international conferences, contacting international experts in the field and searching the references cited in identified studies. We will include analytical epidemiological studies. Two researchers will independently screen identified studies, undertake data extraction and assess risk of bias in eligible studies, while a third reviewer will arbitrate any disagreement. We will use the Effective Public Health Practice Project tool to assess the risk of bias in the studies. We will perform a random-effects meta-analysis to synthesise the evidence. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the strength and quality of the overall evidence with respect to each outcome. ETHICS AND DISSEMINATION: Ethical approval is not required since the study is a systematic review of published literature. Our findings will be reported in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42016048324.

Healthcare costs of asthma comorbidities: a systematic review protocol.

INTRODUCTION: Asthma is associated with many comorbid conditions that have the potential to impact on its management, control and outcomes. These comorbid conditions have the potential to impact on healthcare expenditure. We plan to undertake a systematic review to synthesise the evidence on the healthcare costs associated with asthma comorbidity. METHODS AND ANALYSIS: We will systematically search the following electronic databases between January 2000 and January 2017: National Health Service (NHS) Economic Evaluation Database, Google Scholar, Allied and Complementary Medicine Database (AMED), Global Health, PsychINFO, Medline, Embase, Institute for Scientific Information Web of Science and Cumulative Index to Nursing and Allied Health Literature. We will search the references in the identified studies for additional potential papers. Additional literature will be identified by contacting experts in the field and through searching of registers of ongoing studies. The review will include cost-effectiveness and economic modelling/evaluation studies and analytical observational epidemiology studies that have investigated the healthcare costs of asthma comorbidity. Two reviewers will independently screen studies and extract relevant data from included studies. Methodological quality of epidemiological studies will be assessed using the Effective Public Health Practice Project tool, while that of economic evaluation studies will be assessed using the Drummond checklist. This protocol has been published in International Prospective Register of Systematic Reviews (PROSPERO) database (No. CRD42016051005). ETHICS AND DISSEMINATION: As there are no primary data collected, formal NHS ethical review is not necessary. The findings of this systematic review will be disseminated in a peer-reviewed journal and presented at relevant conferences. PROSPEROREGISTRATION NUMBER: CRD42016051005.

Is selective prenatal iron prophylaxis better than routine prophylaxis: final results of a trial (PROFEG) in Maputo, Mozambique.

OBJECTIVE: To compare routine versus selective (ie, screening and treatment for anaemia) prenatal iron prophylaxis in a malaria-endemic and HIV-prevalent setting, an extended analysis including previously missing data. DESIGN: A pragmatic randomised controlled clinical trial. SETTING: 2 health centres in Maputo, Mozambique. PARTICIPANTS: Pregnant women (≥18 years old; non-high-risk pregnancy) were randomly allocated to routine iron (n=2184) and selective iron (n=2142) groups. INTERVENTIONS: In the routine group, women received 60 mg ferrous sulfate plus 400 µg folic acid daily. In the selective group, women received 1 mg of folic acid daily and haemoglobin (Hb) screening at each visit; with low Hb (cut-off 9 g/dL) treatment (120 mg+800 µg of folic acid daily) for a month. PRIMARY OUTCOMES: preterm birth, low birth weight; secondary outcomes: self-reported malaria, labour complications, caesarean section, perinatal death, woman's death. Nurses collected pregnancy data. Birth data were abstracted from hospital records for 52% of women and traced using various methods and linked with probabilistic matching for 24%. Women's deaths were collected from death registers. RESULTS: Birth data were available for 3301 (76%) of the women. Outcomes were similar in the two groups: preterm births (27.1% in the selective vs 25.3% in the routine group), low birthweight infants (11.0% vs 11.7%), perinatal deaths (2.4% vs 2.4%) and caesarean sections (4.0% vs 4.5%). Women's deaths during pregnancy or <42 days postpartum were more common in the selective group (0.8% among the two best matched women) than in the routine group (0.4%). Extra deaths could not be explained by the cause of death, Hb level or HIV status at recruitment. CONCLUSIONS: Birth outcomes were similar in the two iron groups. There might have been more women's deaths in the selective iron group, but it is unclear whether this was due to the intervention, other factors or chance finding. TRIAL REGISTRATION NUMBER: NCT00488579.

Food consumption and risk of childhood asthma.

BACKGROUND: The consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM)-free diet) in early life and the risk of atopic and non-atopic asthma. METHODS: Food intake of 182 children with asthma and 728 matched controls was measured using 3-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. RESULTS: The diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at 4 yr of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. CONCLUSIONS: Dietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk.

Adherence in a pragmatic randomized controlled trial on prophylactic iron supplementation during pregnancy in Maputo, Mozambique.

OBJECTIVE: Assessing the level of adherence and its determinants is important in appraising the overall effectiveness of trials. The present study aimed to evaluate the extent of adherence and its determinants in a pragmatic randomized controlled trial of Fe prophylaxis during pregnancy in Maputo, Mozambique. DESIGN: A pragmatic randomized controlled trial. SETTING: Two health centres (1° de Maio and Machava) in Maputo, Mozambique. SUBJECTS: Pregnant women (≥12 weeks' gestation, ≥18 years old, non-high-risk pregnancy; n 4326) attending prenatal care consultations at two health centres were randomized to receive routine Fe (n 2184; 60 mg ferrous sulfate plus 400 µg folic acid daily throughout pregnancy) or selective Fe (n 2142; screening and treatment for anaemia and daily intake of 1 mg folic acid). RESULTS: The level of adherence was 79% for having two or more visits, 53% for adequate prenatal care and 67% for complete intake of Fe/folic acid tablets during the trial. The correlation between the adherence measures ranged between 0·151 and 0·739. Adherence did not differ by trial arm, but there were centre differences in adequate prenatal visits and intake of tablets. Older women (>20 years) and those with a history of abortion were more likely to achieve greater adherence, whereas an increased number of previous births decreased the likelihood of adherence. HIV positivity decreased the likelihood of adherence in one trial centre and increased it in the other. CONCLUSIONS: The variation in adherence by trial centre, women's characteristics and outcome measures suggests that adherence in trials fully depends on participants' behaviour and can be increased by paying attention to contextual factors.

A pragmatic randomised controlled trial on routine iron prophylaxis during pregnancy in Maputo, Mozambique (PROFEG): rationale, design, and success.

The effects of prophylactic iron during pregnancy on maternal and child health in developing settings with endemic malaria and high prevalence of HIV remain unclear. This paper describes the rationale, implementation and success of a pragmatic randomised controlled trial comparing routine iron supplementation vs. screening and treatment for anaemia during pregnancy. The setting was two health centres in Maputo, Mozambique. Pregnant women (≥ 12-week gestation; ≥ 18 years old; and not with a high-risk pregnancy, n=4326) were recruited. The main outcomes are preterm delivery and low birthweight. The women were randomly assigned to one of two iron administration policies: a routine iron group (n=2184) received 60 mg of ferrous sulphate plus 400 µg of folic acid daily while a selective iron group (n=2142) had screening and treatment for anaemia and a daily intake of 1 mg of folic acid. The recruitment, follow-up, and collection of follow-up data were successful; both groups were similar to each other in all the trial stages. Collection of delivery data was challenging and data on about 40% of births is missing. These are currently being traced through different hospitals and health centres. The compliance of the study personnel and the women with regard to regular measurement of haemoglobin and intake of the iron and folic acid tablets was high and similar in both trial arms. Taking into account the various constraints encountered, the stages of the present trial prior to delivery were carried out well.