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 For assistance in identifying ongoing or unpublished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. 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. 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. Key messages
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.