What is the aim of this review?
The aim of this Cochrane Review was to determine the effects of fortifying maize flour, corn meal and fortified-maize flour products with iron for anaemia and iron status in the general population. We searched for relevant published studies to answer this question and analysed all relevant information.
It is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of iron deficiency. The evidence is also too uncertain to conclude whether iron-fortified maize flour, corn meal or fortified maize flour products have any effect on reducing the risk of anaemia or on improving haemoglobin concentration in the population. We do not know whether fortifying maize flour with iron reduces anaemia in the general population, as the evidence was very unreliable. No studies reported on any harmful effects.
What was studied in the review?
Approximately 496 million non-pregnant women, 32 million pregnant women, and 273 million children were thought to be anaemic as of 2011. Iron deficiency is considered to be the single most prevalent nutrient deficiency worldwide, but at least half this burden is considered responsive to interventions that involve providing people with iron. Fortification means adding vitamins and minerals to foods to increase their nutritional value. In public health, fortifying staple foods is considered one way of reducing micronutrient deficiencies without changing usual and culturally acceptable diets.
Maize (corn) is one of the world's most important cereal grains. In sub-Saharan Africa, some parts of Southeast Asia and Latin America, where iron deficiency is endemic, maize is a dietary staple for more than 200 million people. Fortification of maize flour with iron (and in some cases, other nutrients) is mandatory in Brazil, Costa Rica, El Salvador, Kenya, Mexico, Nigeria, Rwanda, South Africa, Tanzania, Uganda, the USA and Venezuela.
What are the main results of the review?
We found five relevant studies, but none looked at the effects of maize flour or maize flour products fortified with iron alone. Five studies compared the effects of maize flour or maize-flour products fortified with iron plus other vitamins and minerals versus unfortified maize flours or maize-flour products (not containing iron or any other vitamin and minerals). Three of these five studies randomly divided a collective total of 2302 children aged 2 to 12 years and 130 indigenous women into groups receiving fortified versus unfortified maize flour or corn flour. One study was from Kenya and the other two took place in Mexico. The remaining two studies did not provide data to assess the effects of fortification relative to a comparison group. Three of five of the included studies were funded by public organisations and two by funds granted by private sector to universities. The presence of industry funding for some of these trials did not appear to positively influence results from these studies.
It is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of iron deficiency in the general population. The evidence is also too uncertain to conclude whether iron-fortified maize flour, corn meal or fortified maize flour products have any effect on reducing the risk of anaemia or on improving haemoglobin concentration in the population. We are uncertain whether fortification of maize flour with iron reduces anaemia among the general population.
How up-to-date is this review?
We searched for studies that had been published up to 17 January 2018.
It is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of anaemia or iron deficiency in children aged over 2 years or in adults. Moreover, the evidence is too uncertain to conclude whether iron-fortified maize flour, corn meal or fortified maize flour products have any effect on reducing the risk of anaemia or on improving haemoglobin concentration in the population.
We are uncertain whether fortification of maize flour with iron reduces anaemia among the general population, as the certainty of the evidence is very low. No studies reported on any adverse effects.
Public organisations funded three of the five included studies, while the private sector gave grants to universities to perform the other two. The presence of industry funding for some of these trials did not appear to positively influence results from these studies.
The reduced number of studies, including only two age groups (children and women of reproductive age), as well as the limited number of comparisons (only one out of the four planned) constitute the main limitations of this review.
Approximately 800 million women and children have anaemia, a condition thought to cause almost 9% of the global burden of years lived with disability. Around half this burden could be amenable to interventions that involve the provision of iron. Maize (corn) is one of the world's most important cereal grains and is cultivated across most of the globe. Several programmes around the world have fortified maize flour and other maize-derived foodstuffs with iron and other vitamins and minerals to combat anaemia and iron deficiency.
To assess the effects of iron fortification of maize flour, corn meal and fortified maize flour products for anaemia and iron status in the general population.
We searched the following international and regional sources in December 2017 and January 2018: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE (R) In Process; Embase; Web of Science (both the Social Science Citation Index and the Science Citation Index); CINAHL Ebsco; POPLINE; AGRICOLA (agricola.nal.usda.gov); BIOSIS (ISI); Bibliomap and TRoPHI; IBECS; Scielo; Global Index Medicus - AFRO (includes African Index Medicus); EMRO (includes Index Medicus for the Eastern Mediterranean Region); LILACS; PAHO (Pan American Health Library); WHOLIS (WHO Library); WPRO (includes Western Pacific Region Index Medicus); IMSEAR, Index Medicus for the South-East Asian Region; IndMED, Indian medical journals; and the Native Health Research Database. We searched clinicaltrials.gov and the International Clinical Trials Registry Platform (ICTRP) for any ongoing or planned studies on 17 January 2018 and contacted authors of such studies to obtain further information or eligible data if available.
For assistance in identifying ongoing or unpublished studies, we also contacted relevant international organisations and agencies working in food fortification on 9 August 2016.
We included cluster- or individually randomised controlled trials and observational studies. Interventions included (central/industrial) fortification of maize flour or corn meal with iron alone or with other vitamins and minerals and provided to individuals over 2 years of age (including pregnant and lactating women) from any country.
Two review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies and assessed the risk of bias of the included studies. Trial designs with a comparison group were included to assess the effects of interventions. Trial designs without a control or comparison group (uncontrolled before-and-after studies) were included for completeness but were not considered in assessments of the overall effectiveness of interventions or used to draw conclusions regarding the effects of interventions in the review.
Our search yielded 4529 records. After initial screening of titles and abstracts, we reviewed the full text of 75 studies (80 records). We included 5 studies and excluded 70. All the included studies assessed the effects of providing maize products fortified with iron plus other vitamins and minerals versus unfortified maize flour. No studies compared this intervention to no intervention or looked at the relative effect of flour and products fortified with iron alone (without other vitamins and minerals). Three were randomised trials involving 2610 participants, and two were uncontrolled before-and-after studies involving 849 participants.
Only three studies contributed data for the meta-analysis and included children aged 2 to 11.9 years and women. Compared to unfortified maize flour, it is uncertain whether fortifying maize flour or corn meal with iron and other vitamins and minerals has any effect on anaemia (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.58 to 1.40; 2 studies; 1027 participants; very low-certainty evidence), or on the risk of iron deficiency (RR 0.75, 95% CI 0.49 to 1.15; 2 studies; 1102 participants; very low-certainty evidence), haemoglobin concentration (mean difference (MD) 1.25 g/L, 95% CI −2.36 to 4.86 g/L; 3 studies; 1144 participants; very low-certainty evidence) or ferritin concentrations (MD 0.48 µg/L, 95% CI −0.37 to 1.33 µg/L; 1 study; 584 participants; very low-certainty evidence).
None of the studies reported on any adverse effects. We judged the certainty of the evidence to be very low based on GRADE, so we are uncertain whether the results reflect the true effect of the intervention. We downgraded evidence due to high risk of selection bias and unclear risk of performance bias in one of two included studies, high heterogeneity and wide CIs crossing the line of no effect for anaemia prevalence and haemoglobin concentration.