Approaches to Anemia in Pregnancy

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Approaches to Anemia in Pregnancy Research and Reviews Approaches to Anemia in Pregnancy JMAJ 52(4): 214–218, 2009 Shiro KOZUMA*1 Abstract Even in normal pregnancy, the hemoglobin concentration becomes diluted according to the increase in the volume of circulating blood. Since iron and folic acid in amounts necessary for the fetus are preferentially transported to the fetus, the mother is likely to develop iron deficiency anemia and folic acid deficiency anemia. An adult woman has about 2 g of iron in her body. When a woman becomes pregnant, the demand for iron increases, necessitating an additional 1 g. According to the 2005 Dietary Reference Intakes in Japan, the necessary intake of iron in Japanese women is 10.5 mg/day, whereas it is 20 mg during pregnancy. In regard to folic acid, 240␮g is required daily in non-pregnancy and additional 200␮g is needed in pregnancy. No consensus, however, has been reached as to the influences of maternal anemia on pregnancy. In Japan, hemoglobin concentrations of 11.0 g/dl or less and hematocrit of 33.0% or less are considered as anemia in pregnancy, regardless of the timing in the period of pregnancy, and patients should be treated with iron or folic acid therapy. In the West, the prophylactic routine use of iron and folic acid is not uncommon, but its usefulness is not necessarily established. A recent recommendation in Japan is that a daily dose of 0.4 mg of supplementary folic acid be taken during pregnancy for the purpose of preventing impairment of neural tube closures such as spina bifida in fetuses, regardless of whether or not anemia is present. Key words Iron deficiency anemia, Folic acid deficiency anemia This paper provides an overview of iron defi- Introduction ciency anemia and folic acid deficiency anemia. The description of anemia of other types as a Women go through a variety of physiological complication is left to other papers. Although changes during pregnancy. Changes in the blood anemia is not the main symptom of the HELLP circulatory system are particularly notable, (hemolysis, elevated liver enzymes, and low permitting normal fetal growth. Even in normal platelet count) syndrome, this syndrome is also pregnant women, the hemoglobin concentration described briefly because it is clinically important decreases with dilution according to the increase in pregnancy and delivery. in the volume of circulating blood. Since iron and folic acid in amounts necessary to the fetus are Maternal Changes during Pregnancy preferentially transported to the fetus, the mother is likely to develop iron deficiency anemia and During pregnancy, the circulating plasma volume folic acid deficiency anemia. About 20% of preg- increases linearly to reach a plateau in the 8th or nant women suffer anemia, and most of the cases 9th month of pregnancy. The increment is about are iron deficiency, folic acid deficiency, or both. 1,000 ml, which corresponds to 45% of the cir- The administration of iron and folic acid to preg- culating plasma volume in non-pregnancy. The nant women is a controversial issue, and the policy plasma volume decreases rapidly after delivery regarding this therapy varies among countries. and is then restored to the non-pregnancy level *1 Professor, Postgraduate School of Medicine, University of Tokyo, Tokyo, Japan ([email protected]). This article is a revised English version of a paper originally published in the Journal of the Japan Medical Association (Vol.137, No.6, 2008, pages 1181–1184). 214 JMAJ, July/August 2009 — Vol. 52, No. 4 APPROACHES TO ANEMIA IN PREGNANCY at about 3 puerperal weeks. in the food consumption of Japanese women is Although erythrocytes and hemoglobin also decreasing, and that folic acid deficiency may increase during pregnancy, their increases are occur in pregnancy, where folic acid demand is slow in the initial half of the pregnancy period, increased. causing relative hydremia, and the hemoglobin concentration and hematocrit are lowest in the Influences of Anemia on Pregnancy 5th to 7th month of pregnancy. In the latter half of the pregnancy period, erythrocytes and hemo- Placental weight increases in relation to the globin increase markedly, and the hemoglobin severity of maternal anemia. It is presumed that concentration and hematocrit tend to increase this is because placental growth is promoted to and finally reach normal levels at 6 puerperal compensate for the lack of oxygen delivered weeks. In healthy pregnant women in the US who owing to anemia. In contrast, opinion is divided are taking iron supplements, the 5th percentile as to the influences of anemia on the maternal values of the hemoglobin concentration and body and fetus. No consensus has been reached hematocrit are reported to be 11.0 g/dl and 33.0% in spite of years of research on this issue. at 12 weeks of pregnancy, 10.6 g/dl and 32.0% In developing countries and in retrospective at 16 weeks, 10.5 g/dl and 32.0% at 20 weeks, studies, it has been found that the frequencies 10.5 g/dl and 32.0% at 24 weeks, 10.7 g/dl and of fetal death, low-birth-weight newborns, and 32.0% at 28 weeks, 11.0 g/dl and 33.0% at 32 premature delivery are significantly higher in weeks, 11.4 g/dl and 34.0% at 36 weeks, and cases of maternal anemia.3 On the other hand, 11.9 g/dl and 36.0% at 40 weeks.1 In the US, prospective studies in industrialized countries these values are used as indications of the normal have shown that there is no distinct relationship lower limits. between anemia and perinatal prognosis. Cases An adult woman has about 2,000 mg iron in of severe anemia have been included in studies in the body, 60–70% of which is present in erythro- developing countries or in retrospective studies, cytes, with the rest stored in the liver, spleen, and whereas most cases of anemia are mild or moder- bone marrow. When a woman becomes pregnant, ate in prospective studies in industrialized coun- the demand for iron increases. Specifically, about tries. Therefore, it is possible that severe anemia 1,000 mg more is required, comprising 300 mg for is related to the worsening of perinatal prognosis. the fetus and placenta, 500 mg for increased mater- However, developing countries have critical nal hemoglobin, and 200 mg that compensates problems of poor maternal nutritional status and for excretion. Therefore, an additional 50% of infectious diseases such as malaria. These con- the amount of iron present in the non-pregnant ditions are accompanied with anemia, but also state should be ingested during pregnancy. This include various other factors that can worsen corresponds to an additional intake of 4 mg iron perinatal prognosis, presenting a complex causal per day. Since the absorption of iron in food relationship. Most cases of anemia in Japan are is about 10%, the additional oral iron intake mild, and it is unclear whether such anemia has necessary for a pregnant woman is calculated to any effect on perinatal prognosis. be 40 mg/day. However, according to the 2005 On the other hand, it has been reported that Dietary Reference Intakes in Japan, the neces- high hemoglobin concentrations are a more impor- sary intake of iron in Japanese women with tant issue from the viewpoint of perinatal prog- menstruation is 10.5 mg/day, whereas it is 20 mg nosis. Hemoglobin concentrations of 13.2 g/dl or during pregnancy.2 higher at 13–18 weeks of pregnancy are reportedly Folic acid is plentiful in green and yellow associated with significantly elevated frequencies vegetables, fruits, beens, and liver. About 50% of of perinatal death, low-birth-weight newborns, the iron in the body is stored in the liver, and premature delivery, and pregnancy-induced hyper- deficiency seldom occurs if a well-balanced diet tension syndrome. It has been pointed out that is maintained. According to the 2005 Dietary the absence of decreases in hemoglobin concentra- Reference Intakes in Japan, 240␮g folic acid is tion during pregnancy means a lack of sufficient required daily in non-pregnancy and additional development of hydremia as a manifestation of 200␮g is needed in pregnancy. It has recently normal changes associated with pregnancy, and been pointed out that the amount of folic acid that maladaptation to pregnancy may result in a JMAJ, July/ August 2009 — Vol. 52, No. 4 215 Kozuma S worse perinatal prognosis. use has long been discussed. Although hemato- logic findings, including the hemoglobin concen- Iron Deficiency Anemia tration, are improved by iron therapy, it remains unclear whether such improvement leads to The daily requirement of iron for pregnant better perinatal prognosis. No beneficial effects women is approximately 20 mg. Given the fact have been observed in randomized controlled that the reported mean daily intake of iron in trials,4 similar to the issue as to whether anemia Japanese pregnant women is about 11 mg, many affects perinatal prognosis. Although there is no women are likely to gradually develop iron evidence showing that the prophylactic routine deficiency during pregnancy, resulting in iron use of iron leads to an improved perinatal prog- deficiency anemia. It is said that iron deficiency nosis, the general view in the US seems to be that anemia accounts for 77–95% of all cases of ane- the continuing practice of prophylactic routine mia in pregnancy, occurring at a frequency of iron therapy should not be discontinued, con- about 20%. sidering bleeding at the time of delivery. How- In Japan, pregnant women usually undergo at ever, on the other hand, it also has been pointed least 3 blood tests for maternity health screen- out that iron supplements and increased iron ing.
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