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Maternal and Child Anemia- Why, what works, what needs more work?
1. Maternal and Child Anemia- Why, what works, what needs more work ? Rolf Klemm Johns Hopkins School of Public Health and A2Z Micronutrient and Child Blindness Project Pre-Session: Maternal & Child Anemia Core Group Spring Meeting-April 26, 2010
40. Comparison of current performance and anticipated standard of focused ANC model, Tanzania Von Both, BMC Pregnancy and Childbirth, 2006, 6:22 First Visit Re-visit Current Practice (minutes) Desired based on FANC (minutes) Current Practice (minutes) Desired based on FANC (minutes) Registration 2:10 5:00 1:30 0:00 History taking 4:20 10:00 1:20 5:00 Examination 3:30 8:00 3:00 8:00 Drug Administration 1:00 3:00 1:40 3:00 Immunization 1:40 1:00 1:00 1:00 Health education & counseling 1:30 15:00 0:00 15:00 Total time direct activities 12:20 42:00 6:30 32:00 Welcoming the client 1:00 1:00 1:00 1:00 Documentation of findings 2:00 3:00 1:30 3:00 Total contact time 15:20 46:00 9:00 36:00
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43. Use of iron and folic acid tablets by ANC attendees, Uganda, n=612 High proportion of women have at least 1 ANC visit A2Z Survey (2009) of ANC platforms, unpublished data ~40% who had an ANC visit did NOT receive ANY IFA tablets AND….<10% consumed ≥30 tablets
While iron deficiency is responsible for a large proportion of anemia in pregnancy, it is not the only cause. This graphic depicting intersection circles of anemia, iron deficiency anemia and iron deficiency illustrates 3 main points: Iron deficiency anemia a major but NOT the only cause of anemia. The proportion of anemia due to iron deficiency is likely to vary across geography, population morbidity profile, socioeconomic and other factors. Individuals can be iron deficient without exhibiting anemia. The prevalence of iron deficiency (without anemia) is estimated to be twice that of iron deficiency anemia. Iron deficiency, even without anemia, is associated with health risks. Anemia has multiple precipitating factors that can occur in isolation but more frequently co-occur. In addition to poor bioavailability of dietary iron, intestinal worm infections and particularly blood loss from hookworm infections compound the problem of anemia in many areas. Other important etiologic factors include vitamin deficiencies such as folate and vitamin A deficiency; a variety of infections, including malaria and HIV infection; and hemoglobinopathies. HIV infection is particularly prevalent in sub-Saharan Africa and has been shown to be associated with a median hemoglobin decrease of 5.5 g/l in asymptomatic pregnant women. These factors may be genetic, such as hemoglobinopathies; infections, such as malaria, intestinal helminths and chronic infection; or nutritional, which includes iron deficiency as well as deficiencies of other vitamins and minerals, such as folate, vitamins A and B 12 , and copper. Because iron deficiency makes a large contribution to anemia, global efforts to reduce the anemia burden have largely been directed towards increasing intake of iron through supplementation, food fortification and diversification of the diet.
Knowing the various causes of anemia in a target population is the first step in designing tailored intervention strategies. This table highlights the relative importance of these causes by region. The relative importance of various causes differs by age and sex of the population and setting. The greatest burden of death and disease due to anemia is in Africa and Asia and is associated with the consequences of anemia among pregnant women and young children. In this table we see that iron deficiency is likely to be an important cause of anemia in most regions of the world. Along with iron deficiency, malaria is likely to be an important cause of anemia in Sub-saharan Africa, and of medium importance in Asia.
Nutritional iron deficiency is highest in population segments that are at peak rates of growth, namely, infants, young children and pregnant women. Pregnancy is a time in which the risk for developing iron deficiency anemia is highest, because iron requirements are substantially greater than average absorbable iron intakes. Physiologic demands for iron increase from 0.8 to ≤7.5 ,g absorbed Fe/d. Such demands result in a decline in iron stores during pregnancy and ultimately can produce iron-deficient erythropoiesis (def: process of making RBCs) and anemia because a positive or even n In order to understand how to prevent iron deficiency anemia, it is important to understand its causes and risk factors. 1. Iron deficiency is caused by high iron requirements during critical periods in the life cycle that are not met by iron absorption in diet, especially in populations where with a diet consisting of low dietary bioavailability from monotonous plant-based diets with little meat. The graph shows the iron requirements in miligrams per 1000 kcals (y-axis) by life stages (x-axis). Three life stages have a particularly high demand for iron, and a high risk for iron deficiency if bioavailable iron intake does not meet the high physiologic requirements. Infants—The growth requirements of infants rapidly exhaust the iron accumulated by the fetus during gestation. Infants born to iron deficiency mothers and low birth weight infants are particularly at risk for iron deficiency because they accumulate less iron during gestation and therefore their iron stores are more quickly depleted. Adolescents-- Menstrual blood losses superimposed with increased iron requirements due to the adolescent growth in teenage girls, put them at a higher risk for iron deficiency. Pregnant Women—Iron increases three-fold due to the expansion of the maternal red-cell mass and the growth of the placenta and fetus, yielding a net increase in the requirement for iron of 1 gram which is equivalent to 4 units of blood. This high requirement for iron places pregnant women at a high risk for iron deficiency.
In 2002, the WHO undertook a systematic approach to estimating the burden of disease and injury due to different risks”. It involved the identification, quantification and characterization of threats to human health and provided an overall picture of the relative roles of different risks to human health. Iron deficiency ranked 9 th on the list of risk factors contributing to the global burden of disease, and it is estimated iron deficiency is a risk factor in 1/5 th of perinatal deaths and and 1/10 th of maternal deaths. In total, this amounts to ~800,000 deaths world wide and a loss of ~35 million healthy life years. In high mortality developing countries, iron deficiency is the 6 th largest contributor to death and disability. By focusing and prioritizing interventions that address iron deficiency, major potential health benefits can be achieved. Note to presenter: The Disability Adjusted Life Year or DALY is a health gap measure that extends the concept of potential years of life lost due to premature death (PYLL) to include equivalent years of ‘healthy’ life lost by virtue of being in states of poor health or disability (1). The DALY combines in one measure the time lived with disability and the time lost due to premature mortality. One DALY can be thought of as one lost year of ‘healthy’ life and the burden of disease as a measurement of the gap between current health status and an ideal situation where everyone lives into old age free of disease and
Talking Points: Anemia is one of the most common and widespread disorders in the world, and remains a serious public health problem in both industrialized and non-industrialized countries. Based on the latest WHO estimates, published in 2008, the global prevalence of anemia is 25% and 1.62 billion people are affected. Anemia is extremely common in pregnant women and young children. The global anemia prevalence in pregnant women is 42% which translates into ~56 million pregnant women suffering from this condition. Anemia, which is defined as a hemoglobin concentration <2 standard deviations of the age- and sex specific normal reference, is a commonly used indicator to screen for iron deficiency in population-based surveys, but it is NOT specific for iron deficiency because hemoglobin does not account for other causes of anemia. Data suggest that when anemia prevalence is 20%, iron deficiency exists in 50% of the population and when anemia prevalence is greater than 40%,the entire population suffers from some degree of iron deficiency. Therefore, it is likely that at least 50% or more of the anemia in countries in Africa and Asia is due to iron deficiency. As the graph shows, Africa is home to the highest prevalence of anemia in all risk groups with ~55% of all pregnant women being anemic, followed by Asia where ~47% of pregnant women are anemic. Iron deficiency continues to be a leading cause of anemia in many parts of the world despite significant efforts over the past 30 years to eradicate this nutrient deficiency disorder.
These new analyses suggest that there is a continuous risk relationship between hemoglobin concentration and maternal mortality (depicted in the graph). In other words, mild and moderate—not just severe anemia—has serious consequences for women and children. This new meta-analysis (Stolzfus et al. 2003) shows that correcting anemia of any severity reduces the risk of death. The risks of maternal mortality decreases by about 20% for each 1 g/dL increase in Hb. This decreased risk is continuous over the full range of Hb between 5 and 12, but it is not linear—that is, the decrease in risk is greater at lower Hb concentrations. Questions have been raised about the plausibility of the lack of a threshold between maternal hemoglobin and maternal mortality. There is a plausible argument if one considers that the probability of a maternal death from cardiovascular causes is a function of blood volume, blood loss, cardiac fitness and/or hemoglobin concentration.
A recent study in rural Chinese women, comparing the risk reduction of iron and folic acid supplementation vs. folic acid alone, on birth and neonatal outcomes found a significant increase in the duration of gestation (by 0.23 weeks or 1.6 days) corresponding with a 21% reduction in the risk of preterm delivery (i.e. <37 weeks) and a significant 50% reduction in early preterm delivery (i.e. <34 weeks). There were no significant differences for perinatal mortality, but iron-folic acid was associated with a 54% reduction in early neonatal deaths (i.e. birth to 7 days; RR [95%CI 0.46, 0.21 to 0.98]). This study re-emphasizes that pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximize reductions in neonatal mortality.
The mortality impact of improving iron status during pregnancy appears to last longer than previously recognized based on a study published in October 2009. This is a survival graph (Kaplan Meier curve) showing the probability of survival among children of mothers whose mothers received antenatal micronutrient supplements during a randomized controlled trial conducted in Nepalese. The probability of survival is on the left axis and survival time, from birth to 2,920 days (or ~7 years of age), is on the x-axis. The top (red) line shows the probability of survival among children whose mother received IFSA during pregnancy thru 3 mo post-partum relative to four other micronutrient combinations, with the control group (blue line) at the bottom of the graph. There was a 31% reduction in childhood mortality due to maternal iron and folic acid supplementation (IFSA). This is the first trial to show the long-term effect of maternal IFAS on childhood survival, and extends previously observed beneficial effects on birth size, anemia, infant iron status, and early infant survival.
In animal (rodent) models, early iron defi ciency anaemia—before and after iron repletion— alters brain metabolism and neurotransmission, myelination, and gene and protein profi les.50 Prenatal iron deprivation in non-human primates altered activity, impulsivity, and wariness; postnatal iron deprivation impaired emotional and cognitive development 19 of 21 studies reported poorer mental, motor, socialemotional, or neurophysiologic functioning in infants with iron defi ciency anaemia than those without, despite variation in study sample size and quality In preschool-aged children with iron defi ciency anaemia, improved cognitive outcome with iron treatment has been consistently reported There is conclusive evidence that infants with iron defi ciency anaemia are developmentally at risk in the short term and consistent evidence that they continue to be so in the long term despite iron therapy. Large supplementation trials in infants in developing countries show benefi ts of iron, especially on motor and socialemotional outcomes (table 1), which holds promise that long-term eff ects can be prevented with supplementation. In preschool-aged children with iron defi ciency anaemia, iron treatment improves short-term cognitive outcome.
Illustrative calculations for 10 developing countries suggest that the median value of annual physical productivity losses due to iron deficiency is around $2.32 per capita, or 0.57% of GDP. Median total losses (physical and cognitive combined) are $16.78 per capita, 4.05% of GDP.
Women play a vital role as agricultural producers and as agents of food and nutritional security. Yet relative to men, they have less access to productive assets such as land and services such as finance and extension. A variety of constraints impinge upon their ability to participate in collective action as members of agricultural cooperative or water user associations. In both centralized and decentralized governance systems, women tend to lack political voice. Gender inequalities result in less food being grown, less income being earned, and higher levels of poverty and food insecurity. Agriculture in low-income developing countries is a sector with exceptionally high impact in terms of its potential to reduce poverty. Yet for agricultural growth to fulfill this potential, gender disparities must be addressed and effectively reduced.
In summary, there is a large and strong body of evidence that providing IFAS to mothers in areas of high prevalence of anemia has positive effect on their own risk of mortality, birth weight of their infants, neonatal mortality and possibly post-neonatal child survival.
When an adequate number of iron supplements get consumed by women during pregnancy, their risk of anemia at delivery significantly decreases. In other words, iron supplementation in pregnancy works! These are the results of a systematic review of 14 randomized or quasi-randomized trials. Studies whose relative risks are below 1 (green shaded area) indicate that iron supplementation reduces the risk of anemia. Studies whose risks are above 1 (red shaded area) indicate that iron supplementation increases the risk of anemia. The systematic review of evidence clearly shows consistent beneficial effects across different settings. In other words, increasing iron intake through iron supplements in pregnancy alone will reduce anemia in many settings. But, if efficacy studies show that daily iron supplementation for pregnant women improves hemoglobin concentration and iron status, why is evidence lacking to show that large-scale daily iron supplementation programs in real-world settings can achieve similar impacts? Some critics argue that large-scale maternal iron and/or iron folic acid (IFA) supplementation programs have rarely if ever had substantial impact on anemia prevalence since they are often not implemented as designed. Let’s examine the evidence for this claim.
The Micronutrient Forum initiated a process that critically examined knowledge related to program implementation in real world settings and culminated in a meeting at the UNICEF Innocenti Research Centre in Florence, Italy, in September 2008. The 2008 Innocenti Process involved three main features: (1) critically reviewing the evidence from real-world programs implemented at scale; (2) engaging and giving “center stage” to views of country-level program managers and implementers; and, (3) building consensus among key stakeholder groups on what programs have worked (strength of evidence), what makes those programs work, and what needs more work. A report from this consultation concluded that the major barriers to effective implementation of maternal anemia prevention programs are: Inadequate political support: While most countries have maternal IFA supplementation policies “on the books”, they lack government funds and political support. This low priority results from not recognizing that low hemoglobin concentration in pregnancy, not just severe anemia, is strongly related to maternal and perinatal mortality,and from focusing on curative and facility-based interventions rather than preventive approaches. Therefore, strengthened advocacy is needed to ensure that policy makers are fully aware of the link between maternal anemia reduction and maternal and perinatal survival (i.e. a Millennium Development Goal) and to harness political and funding support for IFA interventions (and other anemia prevention efforts). Low priority for IFA within maternal health programs: Operationally, anemia prevention component is not emphasized in routine ANC. Malaria-endemic countries are strengthening intermittent presumptive treatment (IPT) efforts but IFA distribution and compliance counseling remain weak. Maternal health guidelines, tools, and program implementation strategies often do not emphasize critical operational components such as assuring supplies, training frontline providers to counsel on compliance, and monitoring coverage. The MN community should review why these weaknesses exist and strengthen anemia prevention in existing maternal health programs. Insufficient bundling of interventions to address the multiple causes of anemia: In many settings, parasitic infections such as hookworm and malaria, as well as other nutritional deficiencies, can greatly exacerbate anemia in pregnancy, but anemia prevention guidelines and implementation strategies rarely address these other causes. Inadequate supplies, low utilization, and weak demand: Performance barriers in many maternal IFA supplementation programs include inadequate supplies of IFA tablets (and supplies needed to address other causes of anemia such as intestinal worms and malaria), low utilization of ANC services, and weak demand generation. Operational indicators and feasible methods for collecting, using and acting on them are needed to identify, track, and address these constraints. Community-based delivery platforms to complement the ANC platform are missing: While countries are strengthening the quality and reach of ANC services, many do not have an adequate ANC platform to deliver maternal IFA supplementation to a high proportion of pregnant women on a regular basis. Complementary delivery platforms must be identified, tested, and implemented where ANC services and reach are limited. Preferred strategies should bring IFA supplementation closer to the homes of pregnant womenby using community-based volunteers/workers and private sector outlets combined with social marketing.
So, how can iron supplements reach pregnancy women? Antenatal care (ANC) is a widely used strategy to improve the health of pregnant women, to encourage skilled care during childbirth and to provide iron and folic acid supplements and appropriate counseling messages about maternal care, birth preparation and the use of supplements. The relevant global initiative is called Focussed Antenal Care (FANC). WHO tried several years ago to focus antenatal care to a smaller number of visits and a smaller number of interventions because the assessment was that too many visits were required and too many services were trying to be provided, so FANC was an attempt to focus on the interventions with the strongest evidence base. The number of ANC visits has been reduced to 4, and is focused on health promotion and disease prevention which includes explicitly the reduction of iron deficiency anemia and presumptive treatment of hookworm where prevalent and several other services. But when we look at what is actually happening with antenatal care in low income countries, we see a gap between the current and desired practices. This table shows data from a recent study in Tanzania where they observed the time allocated to antenatal care. Current practice refers to what the observers actually saw in the clinics and the focused antenatal care being a theoretical number of minutes that would be required to deliver the essential interventions in focused antenatal care. Looking at the First Visit columns, the activity with the largest discrepancy from real or current to desired practice is counseling women on all of the things that they are supposed to be getting for antenatal care. In reality, only 1 minute and 30 seconds was given to counseling vs. the 15 minutes that was estimated to be needed. If the follow-up visits, “NO TIME” was spent on counseling. So through all of pregnancy 1 min and 30 sec was the average length of time given to counseling women on all essential ANC services. There are at least two important implications of theses findings: 1. Special attention needs to be given to counseling attitudes and skills during the training for Focused ANC as this component is identified as the major difference between old practice and the new model. Based on reviews by women who participated in the new WHO FANC model, women express satisfaction with nurses taking enough time to help them fully understand the key messages, including the rationale and importance of taking iron and folic acid during pregnancy and managing potential side effects. 2. Investment in additional human resources is necessary in some local settings to ensure the proper implementation of FANC. Given the expected benefits for maternal and perinatal health, it will be a very worthwhile investment.
These are the results of a study conducted in Uganda to assess barriers to effective anemia interventions during antenatal care services conducted in 2002. The fieldwork to assess actual performance was undertaken in four districts with eight health facilities that were selected to represent both government and non-governmental organization (NGO) services. Qualitative and quantitative data collection methods were used; these included focus group discussions (FGDs) with district health teams (DHTs), in-depth interviews with managers of the health facilities and the officers in charge of ANC services, and exit interviews with clients immediately after receiving ANC service. These results are based on exit interviews with 36 health workers and 256 exit interviews with clients. The table displays the most frequent reasons for using ANC services. The main reason women use the ANC services is to get an ANC card because without this card, women facing “pregnancy problems” could not get assistance ready assistance from health units or risk being scolded. In addition, to the ANC card, an illness during pregnancy or suspicion of a pregnancy-related complication is another major reason why mothers attended ANC services. On the study day, 41% of the respondents had come for the ANC in search for medical care for a pregnancy-related complication or sickness, such as acute abdominal pain, dizziness, swollen limbs, severe headache or suspected a risky pregnancy such as multiple pregnancy or abnormal lie of the baby.
The table displays the most frequent reasons for NOT using ANC services. These include: 1.
In addition to knowing the various causes of anemia in a target population, it is important to understand the relationship between the risks of iron deficiency across the critical phases of the life cycle and integrate appropriate interventions into service packages and contact points for each phase. This graphic shows the health risks and potential solutions as a continuum from pre-conception to pregnancy to child birth to early infancy and young childhood. Many reproductive age women in developing countries consume diets of low iron bioavailability and therefore enter pregnancy with no iron stores and less than optimal hemoglobin concentrations. There is a need to increase the iron status of women before pregnancy. This can be accomplished through iron fortification by adding an adequate amount of bioavailable iron to commonly consumed foods or through weekly iron+folic acid supplementation. In areas where hookworm is prevalent, women should receive an appropriate deworming regimen. During the second half of pregnancy, iron requirements begin to increase and continue to do so throughout the pregnancy because of the expansion of the red blood cell mass and the transfer of increasing amounts of iron to both the growing fetus and the placental structures. Iron deficiency anemia during pregnancy increases the risk of maternal mortality possibly through decreased resistance to infection which may contribute to uterine dysfunction or inertia, or through decreased uterine blood flow or low uterine muscle strength which may lead to inefficient uterine contractions and increased blood loss. Antenatal care offers an important platform for providing critical preventive interventions to pregnant women—specifically, iron and folic acid supplementation, deworming and interventions to reduce the risk of giving birth to a low birth weight infant. Maternal iron deficiency also increases the risk of giving birth to a low birth weight infant, delivering a preterm infant, and increases the risk of a maternal, neonatal and child death. At the time of delivery, new evidence indicates that delaying the clamping of the umbilical cord by ~2 minutes can significantly increase the blood flow, and therefore iron stores, to the newborn. The risk of iron deficiency is high during infancy because only about 50% of the iron requirement of a normal six month old can be obtained from breast milk, and by this age the stores received at birth are likely to have been used to support normal functions and growth even in children born at term of well nourished mothers. If the mother is anemic and/or the child is of low birth weight, the stores are depleted much earlier. Continued breastfeeding alone will supply only half of the infant’s iron needs, while the other half, approximately 4 mg/day, must come from complementary foods or an iron containing supplement if iron deficiency anemia is to be avoided. Iron deficiency anemia in infancy is associated with developmental and cognitive delays. Iron supplements, in the form of micronutrient powders, drops or iron-fortified complementary foods (including lipid-based nutrition supplements) can be used to reduce the risk of iron deficiency anemia in infants above 6 months of age.
The major global health initiatives that have relevance for iron deficiency anemia are Making Pregnancy Safe, Saving Newborn Lives, Infant and Young Child Feeding and Iron Fortification. Two other initiatives are important for other causes of anemia. The Presidential Malaria Initiative is essential for reducing the risk of malaria-induced anemia in malaria-endemic areas, and the Neglected Tropical Disease initiative is vital for addressing anemia caused by hook worm and schistosomiasis.
