Description of the condition
Anaemia is a condition in which the number of red blood cells and consequently their oxygen-carrying capacity is insufficient to meet physiologic needs, which vary by age, gender, altitude, smoking, and different stages of pregnancy (WHO 2001). Iron deficiency often precedes anaemia and is one of the most common forms of nutritional deficiencies, particularly among vulnerable groups such as women, children and low-income populations (WHO 2002a). Iron reserves in the body can deteriorate as a result of low dietary intake or poor absorption of iron, which is often associated with cereal based diets (WHO 2001). In addition to iron deficiency, other factors may cause anaemia including blood loss, parasitic infections and deficiencies of vitamin A, folate, vitamin B12, and riboflavin (WHO 2001). Haemoglobin concentrations are used to diagnose anaemia, while serum ferritin, an iron storage protein, and serum transferrin, an iron transport protein, are commonly used as indicators of iron status in populations (WHO 2011b; WHO 2011c).
The postpartum period, sometimes referred as to puerperium, begins just after childbirth and includes the subsequent six weeks (WHO 2010). In normal conditions, maternal iron requirements commonly decline since this nutrient is no longer needed to support fetal and tissue growth and iron losses are reduced by the cessation of menstruation, particularly during prolonged lactation. In addition, only relatively small and decreasing amounts of iron are excreted through breast milk (Shashiraj 2006), which is considered a poor source of iron and cannot be altered by maternal supplementation (WHO 2002b).
Anaemia is one of the most common conditions in women of reproductive age and anaemia during pregnancy has been found to be one of the strongest predictors of postpartum anaemia as iron stores generally tend to remain low several months after delivery, especially if there is augmented blood loss during the delivery and no additional iron intake (Bodnar 2002; Scholl 2000). There are no global figures on the prevalence of anaemia following childbirth, but it is recognised as a common problem throughout the world (Milman 2011; Milman 2012). Studies conducted in the United States of America and in some countries in Europe have reported a prevalence of postpartum anaemia ranging from 10% to 30% (Barroso 2011; Bergmann 2010; Bodnar 2002; Simoes 2004). The prevalence may be higher in low- to middle-income countries, as suggested by data from different age groups (WHO/CDC 2008). For example, the global prevalence of anaemia in pregnant women is 42%, with the highest prevalence found in the WHO Africa region and the highest number of affected pregnant women in WHO South-East Asia region (WHO/CDC 2008).
It is possible that women suffer from multiple concomitant vitamin and mineral deficiencies, although there is not much information on their metabolism during the postpartum period. For calcium, it has been reported that parity and lactation do not affect the long-term risks of low bone density, osteoporosis, or fracture (Kovacs 2011); however, for folate, it has been reported that serum folate concentrations continue to decrease several weeks after delivery, especially when combined with inadequate dietary intakes, and under certain conditions, women may go on to develop megaloblastic anaemia (Haider 2009; Smits 2001).
The consequences of iron deficiency and anaemia during the postpartum period can be serious and have long-term health implications for the mother and her child. Mothers with depleted iron reserves at the time of delivery and following child birth may experience fatigue, altered cognition and depressive symptoms (Breymann 2010). These changes in the mother's emotional and cognitive functioning may in turn affect the interactions with her baby, and have a potentially negative impact on infant behaviour and development (Murray-Kolb 2009). If iron stores are not restored soon after delivery, the negative consequences of postpartum iron deficiency and anaemia may permeate other stages of the reproductive cycle, particularly among those women with short inter-pregnancy intervals (less than 18 months), leading to continued adverse maternal and infant outcomes (Conde-Agudelo 2000; Khoshnood 1998; King 2003; Zhu 1999).
Description of the intervention
Oral iron supplementation refers to the delivery of iron compounds directly to the oral cavity, either as a tablet (regular or dispersible), capsule or liquid. This intervention has been proposed as an efficient and effective approach in public health programmes aimed at improving pregnancy outcomes and enhancing maternal and infant health in different age groups (WHO 2001).
A dosage of 60 mg of elemental iron plus 400 µg (0.4 mg) of folic acid per day is recommended universally for pregnant women, to be continued for three months postpartum, particularly in regions where the prevalence of anaemia is above 40% (WHO 2001). Other international organisations recommend that women who have been identified as having anaemia throughout the third trimester of pregnancy, or who suffer excessive blood loss at delivery or multiple births, should receive supplemental iron up to six weeks postpartum with an oral dose of 60 to 120 mg of elemental iron daily until the anaemia is resolved (CDC 1998; IOM 1990).
How the intervention might work
Iron is absorbed by intestinal cell luminal and basal transporters. It is then bound to proteins that transport it to the bone marrow, muscle and other tissue, where it is taken up by specific receptors and utilised for biologic functions or stored (Andrews 1999). Daily iron supplementation has proven to be effective for increasing haemoglobin concentrations among pregnant and non pregnant women (Fernandez 2011; Pena-Rosas 2009; Yakoob 2011). Some trials suggest that this supplementation regimen could also be effective during the postpartum period although the literature on the contribution of other vitamins and minerals to the women's haematological status and health during the postpartum period is still limited (Correia-Santos 2011; Mitra 2011).
The oral consumption of iron tablets may be associated with unpleasant and sometimes distressing side-effects such as diarrhoea, constipation, nausea and vomiting (WHO 2001). These symptoms increase in severity according to the amount of elemental iron released and whether or not the supplement is taken on an empty stomach or with a meal. The tolerable upper limits for the intake of iron during pregnancy and lactation has been set in 45 mg/day of elemental iron and is based on the gastrointestinal side-effects associated with supplementation (IOM 2001). Alternative intermittent supplementation regimens such as weekly iron-folic acid supplementation have been recommended to prevent anaemia in menstruating women (WHO 2011a). Although their efficacy has not been proven during the postpartum period, they might represent a good alternative to increase iron stores and minimise the negative effects associated with daily supplementation.
In addition to the possible distressing side-effects, daily iron supplementation may be associated with a reduction of zinc and copper absorption, increased oxidative stress and a higher risk of infections. It is plausible that when either zinc or copper are consumed together with iron, their absorption may be impaired due to competition for the same intestinal absorption pathway, but the results are inconsistent (Casanueva 2003; Chung 2002; Gropper 2002; O'Brien 2000; Solomons 1986). It has also been suggested that the iron-rich environment resulting from continued high-dose iron supplementation may cause cell damage (Casanueva 2003; Viteri 2005); however, the clinical significance of this still remains unclear. Finally, it has been proposed that additional iron may exacerbate infections, particularly malaria in areas where it is endemic, as more iron may be available for the parasite's growth, although the mechanisms whereby this may occur are not fully understood (Ekvall 2000; NIH 2011; Oppenheimer 2001). Among pregnant women, some trials have reported an increased risk of infection following iron supplementation but a systematic assessment of the evidence has failed to demonstrate this association (Pena-Rosas 2009).
From the implementation perspective, the period immediately following childbirth may represent a unique opportunity to reach women as they often remain in close contact with healthcare providers. This continuity of care would permit ease of coverage, accessibility, as well as consistency in dosing schedules.
Why it is important to do this review
Iron deficiency and anaemia are important public health problems worldwide, particularly among women of reproductive age. The period following childbirth should not be considered a time of low risk for iron deficiency and anaemia, especially for women living in resource-poor environments who tend to suffer higher rates of morbidity and mortality associated with anaemia (Bodnar 2005; WHO/CDC 2008; WHO 2002a).
Iron supplementation alone or in combination with other nutrients has proven to be efficacious during pregnancy and among other age groups, but as yet there has been no systematic assessment of the benefits or harms of this public health intervention following childbirth, to inform policy making and health practitioners. The potential health gains from improved iron status support the systematic investigation and assessment of iron supplementation during what has previously been a neglected period of the lifecycle.
This review contributes to the body of evidence formed by various Cochrane reviews examining iron and folic acid supplementation as a public health intervention in pregnant and non pregnant women (De-Regil 2010; Fernandez 2011; Haider 2006; Haider 2009; Pena-Rosas 2009; Picciano 2009). It complements the findings of a previously published review that looked at the oral, intravenous or subcutaneous administration of iron, folic acid, erythropoietin or blood transfusion for therapeutic purposes among women with postpartum anaemia (Dodd 2004).