Description of the intervention
Intermittent oral iron supplementation (i.e. one, two or three times
a week on non-consecutive days) is recommended as an alternative
to daily iron supplementation during pregnancy in non-anaemic
pregnant women (WHO 2012). The rationale for intermittent
iron administration is based on two lines of evidence: the first one
is related to the concept that exposing intestinal cells to supplemental
iron less frequently, (e.g. every week in synchrony with
the human mucosal turnover that occurs every five to six days)
may improve the efficiency of absorption since the mucosal cells
are not “blocked” by large amounts of iron as may occur with
daily iron intake (Anderson 2005; Frazer 2003a; Frazer 2003b).
The second line is related to the fact that daily iron supplementation,
by maintaining an iron-rich environment in the gut lumen
and in the intestinal mucosal cells, produces oxidative stress
and is prone to increasing the severity and frequency of undesirable
side effects (Srigiridhar 1998; Srigiridhar 2001; Viteri 1997;
Viteri 1999a).The side effects are probably caused by the challenges
of having to cope with a large non-physiologic bolus dose
of iron, which may also contribute to adverse interactions with infectious
diseases including malaria. Ideally, less side effects would
lead to a higher adherence to supplementation (Viteri 1995; Viteri
1999b), however, some authors have questioned this belief, indicating
that the main reason for the poor compliance with programmes
is the unavailability of iron supplements for the targeted
women (Galloway 1994). The intervention could be an effective
strategy in addressing the problem of forgetfulness and to improve
supplementation compliance (Goonewardene 2012).
An important consideration when providing supplemental iron is
the presence of malaria. Approximately 40% of the world population
is exposed to the parasite and it is endemic in over 100
countries (WHO 2011d) and more than 85 million pregnancies
occur in areas with some degree of Plasmodium falciparum transmission
(Dellicor 2010). It is estimated that about 15 million pregnant
women remain without access to preventive treatment for
malaria (WHO 2014d). Of all the complications associated with
this disease, anaemia is the most common and causes the highest
number of malaria-related deaths. This parasite causes anaemia
by the haemolysis of red blood cells and the compounding suppression
of erythropoiesis (Darnton-Hill 2007). Malaria in pregnant
woman and placental malaria increases the risk of maternal
death, miscarriage, stillbirth and low birthweight with associated
risk of neonatal death (WHO 2011d; WHO 2011e). Intermittent
preventive treatment in pregnancy (IPTp) (i.e. administration of
sulfadoxine-pyrimethamine during the second and third trimester
of pregnancy) can reduce severe maternal anaemia (WHO 2014d)
and is recommended in malaria-endemic areas at each scheduled
antenatal care (ANC) visit for protection against malaria. There
is evidence that high doses of folic acid (i.e. 5000 µg or more)
may interfere with the efficacy of sulfadoxine-pyrimethamine as
an antimalarial (Roll Back Malaria Partnership 2015).
Provision of iron in malaria-endemic areas has been a long-standing
controversy due to concerns that iron therapy may exacerbate
infections, in particular malaria (Oppenheimer 2001). Although
the mechanisms by which additional iron can benefit the parasite
are far from clear (Prentice 2007), the use of daily iron supplementation
has been limited in programme settings, possibly due
to a lack of compliance, concerns about the safety of the intervention
among women with an adequate iron intake, and variable
availability of the supplements at community level.