Anemia of Pregnancy

What is Anemia of Pregnancy?

Anemia of pregnant women is a condition of the human body, characterized by a decrease in the level of hemoglobin, a decrease in the number of red blood cells, the appearance of their pathological forms, a change in the vitamin balance, the number of trace elements and enzymes. Anemia is not a diagnosis, but a symptom, so it is imperative to find out the cause of its development.

According to the WHO, the criteria for anemia in women are: hemoglobin concentration is less than 120 g/l, and less than 110 g/l during pregnancy.

Anemia is one of the most common complications of pregnancy. According to the WHO, the frequency of iron deficiency anemia in pregnant women in countries with different levels of life ranges from 21 to 80%. Over the last decade, due to the deterioration of the socio-economic situation in Russia, the frequency of iron deficiency anemia has increased significantly, despite the low birth rate. The frequency of anemia, according to the Ministry of Health, over the past 10 years has increased 6.3 times.

Anemia of pregnancy in 90% of cases is iron deficient. Iron deficiency anemia is a clinical and hematological syndrome characterized by impaired hemoglobin synthesis due to iron deficiency due to various physiological and pathological processes and manifested by symptoms of anemia and sideropenia.

In the developed countries of Europe, about 10% of women of childbearing age suffer from iron deficiency anemia, 30% of them have a hidden iron deficiency, in some regions of our country this figure reaches 50-60%.

At the end of pregnancy, almost all women have a hidden iron deficiency, and one-third of them develop iron deficiency anemia.

The presence of iron deficiency anemia violates the quality of life of patients, reduces their efficiency, causes functional disorders of many organs and systems. In pregnant women, iron deficiency increases the risk of complications during childbirth, and, in the absence of timely and adequate therapy, leads to fetal iron deficiency.

The doctor needs to know the forms of anemia in which pregnancy is contraindicated.

• Chronic iron deficiency anemia III-IV degree.
• Hemolytic anemia.
• Anemia with bone marrow hypo- and aplasia.
• Leukemia.
• Verlhof disease with frequent exacerbations.

Abortion should be carried out before the period of 12 weeks.

Causes of Pregnancy Anemia

Risk factors for iron deficiency anemia and contraindications for pregnancy

The following main etiological factors for the development of iron deficiency anemia are distinguished.

• Alimentary factor: reduction of iron intake in the body with food (veggie diet, anorexia).
• Burdened somatic history: chronic diseases of internal organs (rheumatism, heart defects, pyelonephritis, hepatitis); liver diseases (impaired iron deposition and transport due to transferrin deficiency); chronic infectious diseases (intense accumulation of iron occurs in the area of ​​inflammation); history of anemia; gastrogenic and enterogenous factors; gastrointestinal bleeding in gastric ulcer and duodenal ulcer, hemorrhoids, intestinal diverticulosis, ulcerative colitis, helminthic invasion; the presence of diseases manifested by chronic nasal bleeding (thrombocytopathy, thrombocytopenic purpura).
• Burdened obstetric and gynecological history: menometrorrhagia; multi-growth women; spontaneous miscarriages in history; the presence of bleeding in previous births; endometriosis; uterine fibroids; prematurity at the birth of the patient herself (since up to 1.5 years the mechanism of iron absorption does not work and the blood formation of the child occurs due to the accumulated reserves of iron).
• Complicated during this pregnancy: multiple pregnancy; early toxicosis; young primiparas; nulliparous over 30 years old; hypotension; exacerbation of chronic infectious diseases during pregnancy; preeclampsia; placenta previa; premature detachment of the placenta.
• Season (in the autumn-winter period there is a deficiency of vitamins).

Pathogenesis during Anemia during Pregnancy

There are the following main mechanisms that contribute to the development of anemia in the body of a pregnant woman:

• The accumulation of interstitial metabolic products during gestation that have a toxic effect on the bone marrow (many authors note that there are significant metabolic disorders in pregnant women with anemia: metabolic acidosis, fluid retention in interstitial tissue, increased copper concentrations, reduced concentrations of vitamins and trace elements – cobalt, manganese , zinc, nickel).
• Changes in hormonal balance during pregnancy (in particular, an increase in the number of E2, which causes inhibition of erythropoiesis).
• Frequent pregnancies and childbirth, multiple pregnancies contribute to the depletion of iron depot in the body.
• The patient has sideropenia (lack of iron in the body).
• Deficiency in the body of a pregnant vitamin B12, folic acid and protein.
• Oxygen starvation, in which there is a violation of redox processes in a woman’s body.
• Immunological changes in the body of a pregnant woman, occurring due to constant antigenic stimulation of the maternal organism from the tissues of the developing fetus (suppression of the T-cell immunity, increased anti-tissue sensitization, accumulation of fine immune aggregates and a low level of complement, reducing the total number of lymphocytes).
• Iron consumption from the depot of the mother’s body, necessary for proper development of the fetus.

During pregnancy, all clinical variants of anemia are diagnosed in the population. However, the vast majority of them are observed casuistically rare. In those cases when the treatment of anemia in a pregnant woman with iron preparations does not produce an effect, it is advisable to clarify the etiology of the pathological process and conduct differential diagnostics with other forms of the disease.

Symptoms of Anemia of Pregnant Women

During pregnancy, childbirth and the postpartum period with anemia

Anemia complicates the course of pregnancy and childbirth, affects the development of the fetus. Even with latent iron deficiency, 59% of women have an unfavorable course of pregnancy and labor.

Features of the course of pregnancy with anemia.

• The threat of abortion (20-42%).
• Early toxicosis (29%).
• Gestosis (40%).
• Hypotension (40%).
• Premature detachment of the placenta (25-35%).
• Placental insufficiency, fetal growth retardation syndrome (25%).
• Preterm delivery (11-42%).

Features of childbirth and the postpartum period with anemia.

• Premature rupture of amniotic fluid.
• Weakness of labor activity (10-37%).
• Premature detachment of the placenta.
• Atonic and hypotonic bleeding in the afterbirth and the early postpartum period (10-51.8%).
• DIC and coagulopathic bleeding (chronic and subacute form of DIC, platelet hypofunction, shortening of aPTTB, an increase in prothrombin index).
• Purulent septic diseases in childbirth and the postpartum period (12%).
• Hypogalactia (39%).
• Antenatal and intrapartum hypoxia.

Perinatal mortality in anemia ranges from 4.5 to 20.7%. Congenital malformations of the fetus occur in 17.8% of cases.

Diagnosis of Pregnancy Anemia

• The main laboratory sign of iron deficiency anemia is a low color index, which reflects the hemoglobin content in the erythrocyte and is a calculated value. Since the production of red blood cells in the bone marrow decreases slightly with iron deficiency anemia, and the synthesis of hemoglobin is disturbed, the color index is always below 0.85.
• Determination of the average hemoglobin content in the erythrocyte (average hemoglobin content). It is calculated by dividing the hemoglobin index (in g / l) by the number of erythrocytes in 1 l of blood, expressed in picograms.
• Erythrocyte count. With iron deficiency anemia, it is reduced.
• The study of the morphological picture of red blood cells. The morphological display of low hemoglobin content in erythrocytes is their hypochromia, which prevails in a peripheral blood smear and is characterized by the presence of a wide enlightenment in the center of the erythrocyte, which is shaped like a bagel or ring. In the normal ratio of central enlightenment and peripheral darkening in the erythrocyte is 1: 1, with hypochromia – 2: 1; 3: 1.

Microcytes predominate in the blood smear – erythrocytes of reduced size, anisocytosis (unequal size) and poikilocytosis (various forms) of erythrocytes are noted.

The number of siderocytes (erythrocytes with granules of iron, detected by special staining) is sharply reduced up to a complete absence, which reflects a decrease in iron stores in the body.

The content of reticulocytes and leukocytes within the normal range can be thrombocytosis, which disappears after the medical elimination of anemia.

• The morphological study of the bone marrow with iron deficiency anemia is not very informative. When using special coloring on iron and counting sideroblasts (containing iron granules ripening erythroblasts), it is noted that the number of the latter is significantly reduced. However, the “gold standard” in the diagnosis of iron deficiency anemia is staining of bone marrow aspirate with iron to determine its reserves (this study is recommended in all unclear cases).
• Determination of serum iron levels. The iron content in the serum is reduced (in women it is normally 12-25 µmol/l).
• Determination of total iron-binding ability of blood serum. This indicator reflects the degree of “starvation” of serum and transferrin iron saturation. The principle of the method is that a deliberate excess of iron is added to the patient’s serum, part of which binds to the protein, and the other, unrelated part is removed. After that, the content of the remaining iron bound to the protein is determined and the amount of iron (in micromol), which can be bound to 1 liter of serum, is calculated. This indicator reflects the total iron binding capacity of the blood serum (the norm is 30-85 mmol/l).

The difference between the indicators of total iron-binding ability of serum and serum iron reflects latent iron-binding ability.

The ratio of serum iron to the total iron binding capacity of the serum reflects the percentage of transferrin saturation with iron (the norm is 16-50%).

• With iron deficiency anemia, there is a decrease in serum ferritin. The decrease in serum is the most sensitive and specific laboratory sign of iron deficiency. Normally, the ferritin content is 15-150 μg/l.
• Estimation of iron reserves in the body is made when determining the content of iron in the urine after the introduction of complexes that bind iron and excrete it with urine (desferal, desferoxamine). The desferal test consists in that after intravenous administration of 500 mg of desferal in a healthy person, 0.8 to 1.2 mg of iron is excreted, while in patients with iron deficiency, this indicator drops to 0.2 mg.
• CBC (hemoglobin, red blood cells, hematocrit, ESR).
• A new strategy in the diagnosis of iron deficiency anemia is to determine the ratio of soluble transferrin receptor to ferritin. This study in the future will replace other diagnostic measures to determine the concentration of iron in the body.

Thus, the presence of iron deficiency anemia can be said in cases of hypochromic anemia, accompanied by:

• a decrease in the content of serum iron (below 12-25 μmol/l);
• an increase in the total iron binding capacity of the blood serum (above 30–85 μmol/l);
• a decrease in the serum ferritin concentration (below 15-150 μg/l);
• an increase in the latent iron binding capacity of the blood serum;
• decrease in the percentage of transferrin saturation with iron (below 16-50%).

It should be noted that the quality of laboratory diagnostics depends on the correctness of the material sampling and the performance of diagnostic methods. The results obtained will not be true if:

• the study is conducted on the background of treatment with iron preparations (it is necessary to diagnose before the start of treatment or not earlier than 7 days after discontinuation of the drugs);
• red blood cell transfusions or washed red blood cells were transfused;
• proper storage of material is not carried out (plastic test tubes with a stopper must be used for the study of serum iron);
• correct material sampling is not made: blood should be taken for examination in the morning, as there are daily fluctuations in serum iron concentrations (in the morning, iron levels are higher).

Treatment of Anemia of Pregnant Women

The most common is iron deficiency anemia. Pregnant women with iron deficiency anemia, in addition to drug therapy, are prescribed a special diet.

Developed certain rules for the treatment of iron deficiency anemia.

The inefficiency of using only dietary diet. It is a well-known fact that 2.5 mg of iron per day is absorbed from food, while drugs are absorbed 15-20 times more.

The greatest amount of iron is found in meat products. The iron contained in them in the form of heme is absorbed in the human body in the amount of 25-30%.

Absorption of iron from other animal products (eggs, fish) is 10-15%, from vegetable products – only 3-5%.

The greatest amount of iron (in mg per 100 g of product) is contained in:

• pork liver (19.0 mg);
• cocoa (12.5 mg);
• egg yolk (7.2 mg);
• heart (6.2 mg);
• calf liver (5.4 mg);
• stale bread (4.7 mg);
• apricots (4.9 mg);
• almond (4.4 mg);
• turkey meat (3.8 mg);
• spinach (3.1 mg);
• veal (2.9 mg).

In the first half of pregnancy, a daily ration is recommended, consisting of software and protein, 80 g of fat and 350-400 g of carbohydrates. The total energy value should be 2600-2800 kcal.

In the second half of pregnancy, the amount of proteins should be increased to 125 g, fat – up to 70-90 g, carbohydrates – up to 400-420 g, the caloric intake in this case is 2900-3050 cal.

Of protein foods, beef, bull liver, tongue, liver and heart, poultry, eggs, and cow’s milk are recommended.

Fats are found in cheese, cottage cheese, sour cream, cream.

Carbohydrates should be replaced by wholemeal rye bread, vegetables (tomatoes, carrots, radishes, beets, pumpkin and cabbage), fruits (apricots, pomegranates, lemons, cherries), dried fruits (dried apricots, raisins, prunes), nuts, berries (currants , wild rose, raspberry, strawberry, gooseberry), croup (oatmeal, buckwheat, rice) and legumes (beans, peas, corn).

Be sure to include fresh greens and honey in the diet.

Requires strict indications for blood transfusion. Hemotransfusion (warm donor blood), red blood cell transfusion and washed red blood cells are procedures that pose a serious danger to the pregnant woman and the fetus due to the high risk of infection (hepatitis B and C, syphilis, AIDS, other viral infections). In addition, iron from transfused red blood cells is very poorly utilized.

The criterion of vital indications for carrying out transfusions of these drugs is not the hemoglobin level, but the patient’s general condition (indications occur 1-2 days before delivery at hemoglobin level below 60 g/l).

Iron preparations should preferably be taken orally. Prevention of the development of iron-deficient anemia in pregnant women at risk for the occurrence of this pathology consists in prescribing small doses of iron preparations (1-2 tablets per day) for 4-6 months, starting from 14-16 weeks of gestation, in courses of 2-3 weeks , with breaks for 14-21 days, only 3-5 courses per pregnancy. At the same time, it is necessary to change the diet in favor of increasing the use of foods containing large amounts of easily digestible iron.

To prevent the development of iron deficiency anemia during pregnancy using the same drugs as for the treatment of this complication.

According to WHO recommendations, all women during the second and third trimesters of pregnancy and for the first 6 months in lactation should take iron supplements.

Iron therapy should be long. The rise of reticulocytes (reticulocyte crisis) is observed on the 8th-12th day of treatment with adequate administration of iron supplements in a sufficient dose, the hemoglobin content increases by the end of the 3rd week of iron deficiency anemia therapy. Normalization of the number of erythrocytes occurs after 5-8 weeks of treatment.

It is known that iron reserves in the body are not affected by the route of its administration – oral or parenteral. At the same time, iron preparations for parenteral use often cause the following adverse reactions:

• allergic reactions, up to anaphylactic shock;
• development of DIC;
• dyspeptic disorders;
• with intramuscular injection may develop infiltrates and abscesses at the injection site.

For oral administration, use of divalent ferrous oxide preparations, since only it is absorbed in the human body. It is necessary that the daily dose of ferrous iron was 100-300 mg. The trivalent iron oxide contained in some preparations in the digestive organs becomes bivalent, which is necessary for the processes of absorption, then is converted in the blood plasma into ferric iron in order to participate in the restoration of hemoglobin level.

In addition to iron, medications for treating iron deficiency anemia contain various components that increase iron absorption (cysteine, ascorbic acid, succinic acid, folic acid, fructose).

For better tolerability, iron supplements should be taken with meals.

It should be borne in mind that under the influence of certain substances contained in food (phosphoric acid, phytin, tannin, calcium salts), as well as with the simultaneous use of a number of medicines (tetracycline antibiotics, Almagel), iron absorption in the body decreases.

It is preferable for pregnant women to prescribe iron supplements in combination with ascorbic acid, which is actively involved in the metabolic processes of this mineral in the body. Ascorbic acid content should exceed 2-5 times the amount of iron in the preparation.

It should be borne in mind that the daily dose of ferrous iron in pregnant women with the presence of mild forms of hyposiderosis should not exceed 50 mg, since at higher doses dyspepsia disorders to which pregnant women are already prone may occur.

According to many researchers, the use of combined iron supplements with vitamin B12 and folic acid without proper indications (without a verified presence of macrocytic – B12 and folic deficiency anemias) during pregnancy is not justified.

On the other hand, the biological connection between iron and folic acid is that iron deficiency in the body can cause impairments in the absorption of folic acid.

Preventing Anemia of Pregnancy

WHO recommendations for the prevention of anemia in pregnant women:

• For effective prevention of anemia, the daily dose is 60 mg of elemental iron and 250 μg of folic acid.
• In the case of treatment of existing anemia, this dose must be doubled.
• Preferred is the use of combined oral iron supplements and folic acid with a prolonged release of iron.
• Do not stop treatment with iron supplements after normalization of hemoglobin and red blood cell levels in the body. Normalization of hemoglobin levels in the body does not mean the restoration of iron reserves in it. For this purpose, WHO experts recommend that after 2-3 months of treatment and the elimination of the hematological picture of anemia, do not stop the therapy, but only halve the dose of the drug used to treat iron deficiency anemia. This course of treatment continues for 3 months. Even having fully restored iron stores in the body, it is advisable to take small doses of iron-containing preparations within six months.

It should be borne in mind that the best way to treat iron deficiency anemia is controlled by the level of transferrin and serum ferritin, and not by the level of hemoglobin and red blood cells.