Interventions throughout life for the prevention or treatmen | Figure 1

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Interventions throughout life for the prevention or treatment of anaemia

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Anaemia (low iron levels in the blood) is a health problem worldwide, caused by nutritional (e.g. nutrient deficiencies) or non‐nutritional (e.g. diseases or genetic disorders) factors. Its health consequences include fatigue, loss of productivity and adverse pregnancy and child outcomes.

Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool and school‐aged children and pregnant and non‐pregnant women. Iron fortification of foods in infants and use of iron pots with children may have benefits for low‐risk populations. Many trials reported the effects of supplementations, but very few reviews focused on fortification or improving diet diversity and quality. Future trials should focus on different types of interventions to increase the variety of foods and dietary quality.

Read the full Cochrane Review here to find out more about the evidence in the following populations:

Infants (6 to 23 months)

Preschool and school‐aged children (2 to 10 years)

Adolescent children (11 to 18 years)

Non‐pregnant women of reproductive age (19 to 49 years)

Pregnant women of reproductive age (15 to 49 years)

Mixed population (all ages)

Read the full Cochrane Review here:

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\ \ Review question\ Does multiple micronutrient fortification improve health?\ Background\ Vitamins and minerals are important for growth and body functioning. Micronutrient deficiencies are common in many populations, and food fortification is one of the interventions to reduce the burden of micronutrient deficiencies and improve health in the general population. Food fortification involves adding micronutrients to processed foods. There have been studies with various single micronutrient fortification, dual micronutrient fortification and multiple micronutrient fortification, including zinc, iron, selenium, vitamin A, vitamin B complexes, vitamin C and vitamin E. We reviewed the evidence about the impact of food fortification with multiple micronutrients (MMNs) on health in the general population.\ Study characteristics\ We included 43 studies (48 papers) in 19,585 participants (17,878 children) in this review. The evidence is current to August 2018. Most of the included studies assessed the impact of food fortification with MMN compared to placebo or to no intervention; two studies compared food fortification with MMN to iodised salt and one study compared food fortification with MMN to food fortification with calcium alone. Most of the studies (36 out of 43) targeted children. Twenty studies were conducted in developing countries. Food used for fortification included staple foods, such as rice and flour; dairy products, including milk and yogurt; non‐dairy beverages; biscuits; spreads; and salt. A high proportion of studies were funded by commercial sources (e.g. manufacturers of micronutrients), which can be associated with finding more beneficial effects than independently‐funded studies.\ Key results\ Food fortification with MMN may reduce anaemia by 32%, iron deficiency anaemia by 72%, micronutrient deficiencies (including iron deficiency by 56%, vitamin A deficiency by 58%, vitamin B2 deficiency by 64%, vitamin B6 deficiency by 91% and vitamin B12 deficiency by 58%). MMN fortification may also improve child growth measured as weight for age and weight for height/length. We are uncertain of the effect of MMN fortification on zinc deficiency and child growth measured as height/length for age. The included studies did not report on any side effects associated with MMN fortification, including deaths and diseases. We are uncertain of the effect of food fortification with MMN compared to iodised salt for iron deficiency anaemia and vitamin A deficiency.\ Quality of the evidence\ The quality of the evidence was low to very low, due to limitations in the study methods that could introduce a risk of bias, high heterogeneity (variation in the results from study to study), and small sample sizes.\ Although the review suggests some positive effects of MMN fortification compared to no intervention, a number of other factors should also be considered. Firstly, there is no information on possible side effects of the MMN fortification. Secondly, we could not perform various subgroup analyses to identify whether MMN fortification is more effective in different population groups, food vehicles, dosage, duration of intervention and geographical region, due to limited number of studies in each subgroup. We performed a subgroup analysis to compare commercial and non‐commercially‐funded studies and did not find a significant difference between their results, although we remain cautious about these findings. Our results are uncertain, due to the low quality of the evidence.](https://app.figure1.com/case-detail/10cd7ce5-4532-4c1d-8f58-25c619d08272)

\ \ Why do we need iron in our diet?\ Iron is an essential mineral found in every cell of the body. It is needed to make haemoglobin, the oxygen‐carrying protein in the blood. Iron molecules in haemoglobin bind to oxygen and carry it from the lungs to all the cells and tissues in the body. Low levels of haemoglobin means the body does not get enough oxygen.\ Anaemia develops when haemoglobin levels in the blood fall too low. Symptoms of anaemia include: tiredness and lack of energy, getting out of breath quickly, pale skin and a greater susceptibility to infections.\ Low haemoglobin levels can be caused by blood loss, pregnancy or not eating enough foods containing iron (iron‐deficiency anaemia). Iron‐deficiency anaemia may be treated by taking iron tablets or eating foods rich in iron.\ Fortified foods\ Adding micronutrients (vitamins and minerals) to foods, whether those micronutrients were originally present or not, is called fortification. Fortifying foods is one way to improve nutrition in a population.\ People living in low‐income countries may not have enough iron in their diet, and may be at risk of anaemia. Adding iron and other nutrients to foods routinely eaten in large quantities, such as flour, is thought to help prevent iron‐deficiency anaemia.\ Why we did this Cochrane Review\ We wanted to find out how adding iron, and other minerals and vitamins, to wheat flour affected the blood iron levels of the general population, and whether fewer people developed anaemia or other health conditions. We also wanted to know if adding iron to wheat flour caused any unwanted effects.\ What did we do?\ We searched for studies that investigated eating any types of food made with wheat flour containing added iron, or foods made with wheat flour without added iron. We then compared the studies with each other, to find out the effects of adding iron to wheat flour on people's health and the levels of iron and haemoglobin in their blood.\ Search date: we included evidence published up to 21 July 2020.\ What we found\ We found 10 studies in 3319 people (aged 2 years and older). The studies lasted from 3 months to 24 months, and took place in Bangladesh, Brazil, India, Kuwait, the Philippines, Sri Lanka and South Africa.\ The studies looked at the effects of:\ · wheat flour containing added iron (with or without other minerals and vitamins) compared with wheat flour without added iron (but with the same other minerals and vitamins);\ · wheat flour containing added iron and other minerals and vitamins compared with wheat flour without any added minerals or vitamins.\ The wheat flours used in the studies contained different amounts of iron: from under 40 mg/kg to over 60 mg/kg.\ We were interested in:\ · how many people had anaemia (defined by low haemoglobin levels);\ · how many people had low levels of iron in their blood (iron deficiency; tested using a biomarker);\ · haemoglobin concentrations in people's blood;\ · how many children had diarrhoea or respiratory infections;\ · how many children died (of any cause);\ · signs of infection or inflammation (the body's response to injury) in children (by testing a biomarker in the blood); and\ · any unwanted effects.\ Most studies had multiple sources of funding; some were partly funded by companies involved in the food, chemical or pharmaceutical industries.\ What are the results of our review?\ Compared with flour without added iron (but with other minerals and vitamins)\ Flour containing added iron (with or without other minerals and vitamins):\ · may reduce anaemia, by 27% (evidence from 5 studies, 2315 people); and\ · probably makes no difference to children's risk of infection or inflammation (2 studies, 558 children).\ It was unclear how flour with added iron affected iron deficiency (3 studies, 748 people), or haemoglobin levels (8 studies, 2831 people).\ Compared with flour without any added minerals or vitamins\ Flour containing added iron (with other minerals and vitamins) probably reduced iron deficiency (3 studies, 382 people). It was unclear from the studies how flour containing added iron affected anaemia (2 studies, 317 people) or haemoglobin levels (4 studies, 532 people).\ No studies reported information about unwanted effects, or how many children died, or had diarrhoea or respiratory infections.\ Our confidence in our results\ Our confidence is moderate to low that adding iron to flour probably reduces iron deficiency and anaemia. The studies appeared to show fewer people with iron deficiency and slightly higher haemoglobin levels associated with flour with added iron, but the results varied widely, so we are uncertain about the effect. These results might change if further evidence becomes available. We found limitations in the ways some of the studies were designed and conducted, and this could have affected their results.\ Key messages\ Adding iron to wheat flour may lead to fewer people with anaemia or low blood‐iron nutrition in the general population.\ We do not know if adding iron to wheat flour causes any unwanted effects, because no studies looked at these.](https://app.figure1.com/case-detail/12215890-121a-4e09-a056-e0a352ba3866)

\ \ What is the issue?\ People with chronic kidney disease requiring dialysis are at risk of developing malnutrition for many reasons and often do not eat enough because their appetite is poor. Oral nutritional supplements are commonly provided to people who do not eat enough to meet their needs. Provision of nutritional supplements to dialysis patients requires careful consideration of potassium, phosphate and fluid limits.\ What did we do?\ We aimed to determine if giving oral protein‐based nutritional supplements improved serum albumin levels and other measures of nutrition.\ What did we find?\ A total of 1278 people took part in 22 studies that were included in this review to investigate the effects of oral protein‐based nutritional supplements. All participants were adults on maintenance dialysis (79% haemodialysis and 21% peritoneal dialysis). The studies lasted from one to 12 months. The findings suggest that giving oral protein‐based nutritional supplementation probably results in a slightly greater increase in albumin level and may improve prealbumin level and mid‐arm muscle circumference. The increase in albumin level was more evident in participants who were on haemodialysis and in those who were malnourished. It is uncertain whether oral protein‐based nutritional supplementation affects potassium and phosphate levels. Oral protein‐based nutritional supplements may result in little or no difference in the risk of developing abdominal symptoms.There were some differences between the quality of the studies and their designs.\ Conclusions\ The authors conclude that oral protein‐based nutritional supplements appear to be effective in improving some nutritional markers in people who need dialysis; however, it remains uncertain whether these results translate to meaningful outcomes for this population. More research is required to determine the cost‐effectiveness of this treatment, and if it can bring benefit to patients such as feeling better and living longer.](https://app.figure1.com/case-detail/229dacdc-13fd-4c8d-aeb4-3b19a1e2521f)

\ \ We analysed evidence from randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) investigating probiotic supplements alone or in combination with drug or non‐drug interventions for preventing gestational diabetes mellitus (GDM).\ What is the issue?\ GDM is a condition where the mother develops high blood sugar levels, usually after 13 weeks of pregnancy. GDM is different from type 2 diabetes in that blood sugar levels are normal before pregnancy, and the levels usually return to normal after pregnancy. GDM is associated with an increased risk of developing type 2 diabetes later in life. Women with GDM are at increased risk of high blood pressure with protein in the urine (pre‐eclampsia) and instrumental delivery or caesarean section. Their infants are more likely to be born large for their gestational age. Probiotics are 'good bacteria' that are usually taken in the form of capsules or drinks to add to the gut bacteria. We are dependent on our gut bacteria to help digest our food, produce certain vitamins, regulate our immune system and keep us healthy by protecting us against disease‐causing bacteria. Probiotics could change a person's metabolism and play a role in the prevention of GDM.\ Why is this important?\ Women who are overweight or obese, had GDM in a previous pregnancy or have an immediate family member with diabetes are at increased risk of GDM. Current treatment for GDM includes diet with or without medication but does not always prevent the problems associated with GDM. Probiotics could be a simple method for preventing GDM. This review looked at whether there is evidence to show if this is true.\ What evidence did we find?\ We searched for evidence from randomised controlled trials in March 2020 and identified seven studies with 1647 pregnant women comparing probiotics with inactive placebo (pretend treatment). Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. The overall risk of bias was low except for one study where the risk of bias was unclear.\ It is unclear how probiotics affect the risk of developing GDM due to the wide variation in the results of six studies (1440 women, low‐quality evidence). Probiotics increase the risk of developing pre‐eclampsia (4 studies, 955 women; high‐quality evidence). Probiotics make little to no difference to the risk of needing a caesarean section (6 studies, 1520 women; high‐quality evidence), and probably make little to no difference to weight gain during pregnancy (4 studies, 853 women; moderate‐quality evidence) or to the risk of giving birth to a big baby (4 studies, 919 women; moderate‐quality evidence). None of the studies reported information about the risk of perineal trauma (tears during vaginal birth or a surgical incision (episiotomy)), postnatal depression or developing subsequent diabetes.\ We do not know if probiotics affect the infant having medical problems after birth because of the variation in results between studies (2 studies, 623 infants; low‐quality evidence). It is also uncertain how probiotics affect infant death (either before birth or as a newborn) (3 studies, 709 infants; low‐certainty evidence), low blood sugar (2 studies, 586 infants; low‐certainty evidence) or body fat (2 studies, 320 infants; low‐certainty evidence). None of the studies reported information about the risk of infants developing diabetes or long‐term conditions that affect brain development.\ What does this mean?\ Low‐quality evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high‐quality evidence suggests that probiotics probably increase the risk of pre‐eclampsia. Therefore, there is currently evidence of possible harm with little observed benefit for widespread use of probiotics in pregnancy.\ There are eight studies currently ongoing that may help to provide more clarity on the effects of probiotics. It is also important to explore the relationship between probiotics and pre‐eclampsia further.](https://app.figure1.com/case-detail/4dda97c1-6e16-4a50-85af-b81dfd072f2c)

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