Anemia in Pregnancy: Magnitude of ProblemCHAPTER 1

Anemia is one of the most commonly encountered medical disorders during pregnancy. In developing countries it is a cause of serious concern as, besides many other adverse effects on the mother and the fetus it contributes significantly to high maternal mortality. According to United Nations declaration 1997, anemia is a major public health problem that needs total elimination. It is estimated that globally two billion people suffer from anemia or iron deficiency.¹

Exact data on prevalence of anemia in women is not available but a crude estimate is that 500 million women between 15 and 49 years of age worldwide are anemic.² According to World Health Organization estimates, up to 56% of all women living in developing countries are anemic.³ In India, National Family 3Health Survey-2 in 1998 to 99 shows that 54% of women in rural and 46% of women in urban areas are anemic. In US 12 to 16% non pregnant women between ages 16 to 48 are iron deficient and 2 to 4% women are anemic.⁴

Anemia is responsible for adverse obstetric outcome in large number of women in developing countries. More than 1000 severely anemic young women are reported to die every week because of their inability to cope with the stress of childbirth.¹ In India 16% of maternal deaths are due to anemia.⁷ Anemia is also a contributory factor in many maternal deaths due to other causes. FOGSI-WHO study on maternal mortality revealed that 64.4% of women who died had hemoglobin of 8 gm% and 21.6% had hemoglobin level of less than 5 gm%.⁸ Cardiac failure, cerebral anoxia, infections especially puerperal sepsis and inability to stand even slight blood loss during pregnancy or delivery are seen in these women, especially in those who are severely anemic. Abortions, preterm labor, IUGR and low birth weight babies are more common in anemic women. There is evidence that time of onset of anemia or iron deficiency affects the obstetric outcome. Anemia in early pregnancy, that is, before second trimester is more likely to 5be associated with preterm and low birth weight babies. A 2-fold increase in the risk of preterm birth has been observed in women who have anemia in mid pregnancy.⁹ Newborns of iron deficient women have lower iron stores. Lower APGAR scores, neurological and mental impairment has also been reported in some but not all studies. Hypertrophy of placenta, a consequence of anemia, and an increased placental: fetal ratio has been suggested to be a predictor of diabetes and cardiovascular disease in later life.

According to WHO, hemoglobin level below 11 gm/dl in pregnant women constitutes anemia and hemoglobin below 7gm/dl is severe anemia. The Centers for Disease Control and Prevention (1990) defines anemia as less than 11 gm/dl in the first and third trimester and less than 10.5 gm/dl in second trimester. Serum Ferritin of 15 micro gm/L is associated with iron deficiency anemia.

The anemia of pregnancy is multi-factorial. Nutritional anemia is the commonest, especially in the developing countries. Various factors responsible for anemia during pregnancy include the following:

About 1000 mg of iron is required during pregnancy; 500 mg for RBC expansion, 300 mg for fetus and placenta and the rest for the growing uterus. As a result of amenorrhea there is a saving of about 150 mg of iron and therefore, about 6850 mg of extra iron is required during pregnancy. Diet alone can not provide this extra iron and stores which have around 500 mg of iron get depleted. But if iron stores are already deficient, iron deficiency anemia manifests.

Total iron in an adult woman is about 50 mg/kg weight as compared to 70 mg/kg in an adult male. 20% of total iron is in the stores (Reticulo-endothelial system-liver, spleen, bone marrow), Majority of the women in child bearing age have deficient iron stores because of blood loss from menstruation. Menorrhagia depletes the iron stores further in many women of child bearing age. In multigravida repeated child bearing does not give them time to replenish iron store in between the pregnancies thus perpetuating the anemia. In an iron deficient woman, it may take a year for hemoglobin to come to pre pregnancy value while iron supplementation restores it in 5 to 7 days postpartum.¹⁰

Deficient or defective intake of iron and other hematopoietic factors during pregnancy due to poverty, ignorance or absorption disorders lead to nutritional deficiency during pregnancy. Deficiency of iron, folic acid or both is common. Multiple micronutrient deficiencies are often encountered along with calorie—protein malnutrition leading to severe anemia and hypoproteinemia. Deficient iron stores in infancy, childhood, adolescence and in childbearing years perpetuate anemia during pregnancy and beyond. Vitamin B₁₂ deficiency, although a 7rare cause of anemia during pregnancy, is sometimes seen in strict vegans.

Chronic blood loss due to various causes also contributes to the iron deficiency anemia. Malaria which is endemic in certain parts of the world causes anemia by hemolysis. Some parasitic infections, e.g. hookworm, trichuriasis, amoebiasis and vesical and intestinal schistosomiasis cause blood loss directly and lead to iron deficiency anemia.

Infections may impair hematopoiesis and consequently cause anemia. Chronic and recurrent infections or inflammations, as the cause of anemia have been reported to rank second only to iron deficiency in prevalence. Acute infections can also lead to anemia.

Although nutritional anemia accounts for most of the anemia that occurs globally in underprivileged environments, several other possible causes could also be present.

Although easy to prevent and treat, nutritional anemia, the commonest anemia, continues to affect millions of women throughout the world. Improving nutritional status of woman through diet, the most desirable and sustainable strategy, entails improvement of economic as well as social status of woman. Elimination of poverty and accessibility to good quality food for all is still a distant reality.

The strategies to prevent nutritional anemia, the commonest anemia during pregnancy, aim at improving diet, increasing bioavailability of dietary iron, prevention and treatment of 9infections like hookworm and malaria and iron folic acid supplementation. Food fortification and genetic modification of food are some of the other strategies being evaluated.

Improving dietary intake of macro as well as micronutrients is obviously the most acceptable strategy to prevent nutritional anemia. Protein calorie malnutrition is often associated with anemia in developing countries.

Since in most of the pregnant women it is not possible to meet the increased demands of iron during pregnancy through diet despite the increased absorption of iron (from 1 to 2 mg/day to 6 mg/day) in later part of pregnancy, iron and folic acid supplementation is a widely accepted strategy.

Supplementation with iron (and folate) alone may be sufficient for well nourished pregnant woman but may not be effective in correcting nutritional anemia in pregnant women with multiple micronutrient deficiency. Consequently, where multiple nutrient deficiencies are common, a more appropriate multiple micronutrients supplement formulation is indicated.

Food fortification has been found to be one of the most effective and simple ways to deliver micronutrients to all sections of the population in many developed and developing countries. As a result of the global efforts of WHO, UNICEF, WB and CDC, flour fortification has extended internationally.

Genetically modified foods with high iron content have the potential for improving the nutritional status of undernourished populations. Rice, a poor source of iron, has been genetically modified to decrease the phytate content, to increase the iron content and to increase the amount of amino acid cysteine which enhances the absorption of iron from the intestine. 13Benefits and risks, if any of biomanipulations are being evaluated.

Preventive measures against hookworm and malaria should also be considered in populations with high prevalence of these conditions. Antihelmenthics like mebendazole can be given during pregnancy except in first trimester.

Since women with severe anemia are most vulnerable to adverse pregnancy outcomes, its detection and management deserves highest priority.

Some of the earlier studies questioned the routine administration of iron to all pregnant women. Healthy women in industrial countries with good diets and adequate iron stores did not show any benefit from supplemental iron in terms of birth weight, length of gestation, maternal and neonatal morbidity and mortality. Most of the women in child bearing age however do not have adequate stores. More recent studies have shown beneficial effects of iron supplementation during pregnancy especially on the fetus. Women who receive daily antenatal iron supplementation are less likely to have iron-deficiency anemia at term.¹⁷ WHO recommends 30 to 60 mg/d for iron replete and 120 to 240 mg /d in women with absent iron stores. ACOG recommendations for prevention of iron deficiency anemia in pregnancy include administration of 30 mg of iron per day along with encouraging iron rich diet and diets that enhance iron absorption. However, recent studies have shown an increase in the risk of developing type 2 diabetes mellitus 15with moderately increased iron stores¹⁸ and increased ferritin levels have been shown to be risk factor for development of diabetes mellitus both in pregnant and non-pregnant women. Increased oxidative stress with increased iron stores has also been documented. Risk benefit of increased maternal status and stores from prophylactic iron supplementation is being evaluated.

High levels of hemoglobin, hematocrit, and ferritin have been reported to be associated with an increased risk of fetal growth restriction, preeclampsia and preterm delivery. Likely explanation for increased hemoglobin in IUGR and pre-eclampsia is failure of plasma expansion due to underlying pathology rather than iron supplementation. High serum ferritin levels observed in preterm labor may be due to inflammation or infection.