Anemia in Pregnancy

Anemia in pregnancy is a pathological condition characterized by a decrease in the number of erythrocytes and / or hemoglobin in a unit of blood volume. The frequency of this complication of pregnancy is observed, according to various sources, in 18-75% (56% on average) of women.

[1], [2]

Iron deficiency anemia in pregnant women

Iron deficiency anemia in pregnancy is a disease in which there is a decrease in the level of iron in the blood serum, bone marrow and depot organs, as a result of which the formation of hemoglobin, and later erythrocytes, hypochromic anemia and trophic disorders in tissues is disrupted.

This complication adversely affects the course of pregnancy, childbirth and the fetus. Low iron content in the body leads to a weakening of the immune system (phagocytosis is inhibited, the response of lymphocytes to stimulation with antigens weakens, and the formation of antibodies, proteins, and the receptor apparatus of cells, which includes iron) is limited.

It should be borne in mind that in the first trimester of pregnancy the need for iron is reduced by stopping its loss during menstruation. During this period, the loss of iron through the digestive tract, skin and urine (basal losses) is 0.8 mg / day. From the second trimester and until the end of pregnancy, the need for iron increases to 4-6 mg, and in the last 6-8 weeks. Reaches 10 mg. This is primarily due to the increased consumption of oxygen by the mother and the fetus, which is accompanied by an increase in the volume of circulating plasma (about 50%) and the mass of erythrocytes (about 35%). To ensure these processes, the mother's body needs about 450 mt of iron. In the future, the requirements for iron are determined by the mass of the fetal body. So, with a body weight of more than 3 kg, it contains 270 mg, and the placenta - 90 mg of iron. During childbirth with blood, a woman loses 150 mg of iron.

Under optimal feeding conditions (intake of iron in bioavailable form - veal, poultry, fish) and consumption of sufficient amount of ascorbic acid, iron absorption does not exceed 3-4 mg / day, which is less than physiological needs during pregnancy and lactation.

Causes of iron deficiency anemia during pregnancy

The causes that can cause anemic syndrome are manifold, and conditionally they can be divided into two groups:

1. They existed before the present pregnancy. This is a limited supply of iron in the body before pregnancy, which can be caused by conditions such as inadequate or inadequate nutrition, hyperpolymenorrhea, the interval between births of less than 2 years, four births and more in history, hemorrhagic diathesis, diseases that are accompanied by a violation of iron absorption (atrophic gastritis, condition after gastrectomy or subtotal resection of the stomach, condition after resection of a large part of the small intestine, malabsorption syndrome, chronic enteritis, amyloidosis of the intestines etc.), the constant intake of antacids, the diseases of redistribution of iron (systemic connective tissue diseases, purulent-septic conditions, chronic infections, tuberculosis, malignant tumors), parasitic and helminthic invasions, liver pathology, violation of the deposition and transport of iron in violation of transferrin synthesis (chronic hepatitis, severe course of gestosis).
2. Arisen during this pregnancy and existing in a pure form or overlapping the first group of causes of anemia. This is a multiple pregnancy, bleeding during pregnancy (bleeding from the uterus, nose, digestive tract, hematuria, etc.).

[3], [4], [5], [6]

Symptoms of iron deficiency anemia during pregnancy

In the case of a lack of iron in the body, anemia is preceded by a long period of latent iron deficiency with clear signs of a reduction in its stocks. With a significant decrease in hemoglobin levels, the symptoms due to hemic hypoxia (anemic hypoxia) and signs of tissue deficiency of iron (sideropenic syndrome) come to the fore.

Anemic hypoxia (actually anemic syndrome) is manifested by general weakness, dizziness, pain in the heart, paleness of the skin and visible mucous membranes, tachycardia, dyspnoea with physical exertion, irritability, nervousness, memory and attention loss, appetite impairment.

Deficiency of iron is characterized by sideropenic symptoms: fatigue, memory impairment, muscular system damage, taste distortion, loss and fragility of hair, brittle nails. Patients often observe dryness and cracking of the skin on the hands and feet, angular stomatitis, cracks in the corners of the mouth, glossitis, as well as lesions of the digestive tract - hypo- or antacid.

Diagnosis of iron deficiency anemia during pregnancy

When making a diagnosis, it is necessary to take into account the period of pregnancy. Normally, hemoglobin and hematocrit amount decrease in the I trimester of pregnancy, reach minimum values in II and then gradually increase in the III trimester. Therefore, in I and III trimester anemia can be diagnosed with a hemoglobin level below 110 g / l, and in the second trimester - below 105 g / l.

It should be borne in mind that a decrease in hemoglobin concentration is not a proof of iron deficiency, so an additional study is needed which, depending on the laboratory's capabilities, should include two to ten of the following tests,

The main laboratory criteria for iron-deficiency anemia: erythrocyte microcircosis (combined with aniso- and poikilocytosis), erythrocyte hypochromia (color index <0.86), decrease in mean hemoglobin content in erythrocyte (<27 pg), decrease in mean hemoglobin concentration in erythrocyte (<33% ), a decrease in the average volume of erythrocytes (<80 μm ³ ); reduction of serum iron (<12.5 μmol / l), a decrease in serum ferritin concentration (<15 μg / l), an increase in the total iron binding capacity of the serum (> 85 μmol / l), a decrease in ferroferrin saturation with iron (<15%), protoporphyrins in erythrocytes (<90 μmol / l).

It is mandatory to determine the color index and identify microcytosis in the blood smear (the simplest and most affordable methods). It is desirable to determine the concentration of serum iron.

[7],

Treatment of iron deficiency anemia during pregnancy

Treatment of iron deficiency anemia has its own characteristics and is determined by the degree of its severity and the presence of concomitant extragenital diseases and complications in pregnancy.

Defining therapeutic tactics, it is necessary:

• eliminate the causes of iron deficiency (gastric, intestinal, nasal bleeding, as well as from birth canals, hematuria, a breach of the blood coagulation system, etc.);
• avoid foods that reduce the absorption of iron in the body of the patient (cereals, bran, soy, corn, water with increased content of carbonates, hydrocarbons, phosphates, tetracyclines, almagel, calcium, magnesium, aluminum, red wine, tea, milk, coffee) ;
• recommend oral intake of iron preparations (except for cases when taking the drug inside is contraindicated). Prophylactic intake of iron preparations (60 mg) is necessary for all pregnant women since the second trimester of pregnancy and for 3 months. After childbirth.

The therapeutic daily dose of alimentary iron for oral intake should be 2 mg per 1 kg of body weight or 100-300 mg / day.

When choosing a particular iron-containing drug, it should be taken into account that among iron ionic compounds, it is preferable to use preparations containing ferrous iron, since its bioavailability is significantly higher than trivalent. It is advisable to prescribe preparations with high iron content (1-2 tablets correspond to the daily requirement) and drugs with delayed release (retard forms), which allows to maintain a sufficient concentration of iron in the serum and reduce gastrointestinal by-products effects.

It is necessary to use combined preparations, the additional components of which prevent the oxidation of ferrous iron to trivalent (ascorbic, succinic, oxalate acids), promote absorption of iron in the intestine (amino acids, polypeptides, fructose), prevent the irritating effect of iron ions on the mucosa of the digestive tract (mucoproteosis) weaken the antioxidant effect of ferrous iron (ascorbic acid and other antioxidants), support the brush border of the mucous membrane and small intestine in an active state (folic acid).

Contraindications to the intake of iron preparations inside are iron intolerance (constant nausea, dizziness, diarrhea), a condition after resection of the small intestine, enteritis, malabsorption syndrome, peptic ulcer exacerbation, ulcerative colitis or Crohn's disease.

In the presence of contraindications for oral administration of iron preparations, parenteral administration of preparations that contain ferric iron is prescribed. In the case of parenteral administration, the daily dose of iron should not exceed 100 mg.

In connection with the risk of liver hemosiderosis, it is advisable to treat parenteral iron preparations under the control of the content of serum iron.

Side effects of iron-containing drugs

When taken orally, they are associated mainly with local eruptive effects: nausea, epigastric pain, diarrhea, constipation, minor allergic reactions (rash on the skin). With parenteral administration, local tissue irritation, as well as pain in the heart, arterial hypotension, arthralgia, lymphadenopathy, fever, headache, dizziness, infiltration of the injection site, anaphylactoid reactions, anaphylactic shock are possible.

There is evidence indicating a more pronounced effect of ferrotherapy when combined with the intake of folic acid, human recombinant erythropoietin, multivitamin preparations containing minerals.

If in the late term of pregnancy (more than 37 weeks) there is a severe symptomatic anemia, it is necessary to solve the problem of transfusion of erythrocyte mass or washed erythrocytes.

Prevention of iron deficiency anemia is indicated in pregnant women at risk. It is based on the rational nutrition and use of iron preparations. The food should be high-grade, contain a sufficient amount of iron and protein. The main source of iron for a pregnant woman is meat. Better absorbed iron in a gem form and worse - from plant foods,

To improve the absorption of iron in the diet include fruits, berries, green vegetables, juices and fruit drinks, honey (dark varieties).

The use of meat and foods that contribute to the improvement of iron absorption should be divided in time with tea, coffee, canned foods, cereals, milk and fermented milk products containing compounds that suppress iron absorption.

With anemia, decoctions or infusions of rose hips, elderberry, black currant, strawberry and nettle leaves are recommended.

Preventing iron deficiency anemia during pregnancy

Prevention of iron deficiency anemia also consists in the continuous intake of iron preparations (1-2 tablets per day) during the III trimester of pregnancy. You can apply iron preparations in courses for 2-3 weeks. With interruptions for 2-3 weeks, only 3-5 courses during the entire pregnancy. The daily dose for the prevention of anemia is about 50-60 mg of ferrous iron. Improvement of erythropoiesis is facilitated by the inclusion in therapy of ascorbic and folic acid, vitamin E, B vitamins, trace elements (copper, manganese).

B12-deficiency anemia in pregnancy

Anemia is caused by a deficiency of vitamin B ₁₂, characterized by the appearance in the bone marrow megaloblasts, intramedullary erythrokaryocytes destruction, decreased red blood cell count (to a lesser degree - hemoglobin), thrombocytopenia, leukopenia and neutropenia.

In the human body, up to 6-9 μg of vitamin B ₁₂ can be absorbed per day , the content of which is normally 2-5 mg. The main body in which this vitamin is contained is the liver. Since not all vitamin B ₁₂ is absorbed from food , it is necessary to get 3-7 μg of vitamin per day in the form of a drug.

[8], [9],

Causes of B12-deficiency anemia in pregnancy

Deficiency of vitamin B ₁₂ arises from the inadequacy of the synthesis of the internal factor of the Castle, necessary for absorption of the vitamin (observed after resection or removal of the stomach, autoimmune gastritis), disturbances of absorption processes in the ileum of the intestine (ulcerative colitis, pancreatitis, Crohn's disease, dysbacteriosis, bacteria in the caecum, helminthiases (wide ribbons), conditions after resection of the ileum part of the intestine, deficiency of vitamin B ₁₂ in the diet (lack of animal products chronic alcoholism, and the intake of certain medications.

In the pathogenesis of B12-deficient anemia in pregnancy, there are changes in hematopoiesis and epithelial cells associated with impaired thymidine formation and cell division (cells increase in size, megaloblastic hematopoiesis).

[10], [11]

Symptoms of B12-deficiency anemia in pregnancy

With a deficiency of vitamin B _¹², changes occur in the hematopoietic tissue, digestive and nervous systems.

Deficiency of vitamin B ₁₂ manifests itself as signs of anemic hypoxia (rapid fatigue, general weakness, palpitation, etc.). With severe anemia, jaundice is seen in the sclera and skin, signs of glossitis.

Occasionally, hepatosplenomegaly occurs and gastric secretion decreases

Characteristic sign of _12- deficient anemia is the defeat of the nervous system, the symptoms of which are paresthesia, sensitivity disorders with pain sensations, a feeling of cold, numbness in the limbs, crawling crawling, often muscle weakness, dysfunction of the pelvic organs. Very rarely observed mental disorders, delusions, hallucinations, in very severe cases - cachexia, areflexia, persistent paralysis of the lower limbs.

Diagnosis of B12-deficiency anemia in pregnancy

Diagnosis is based on the determination of the vitamin B ₁₂ content (decreases below 100 pg / ml at a rate of 160-950 pg / l) against the background of the presence of hyperchromic macro-utes, in erythrocytes - Jolly's body, increased ferritin level, decrease in haptoglobin concentration, increase in LDH. The diagnostic criteria also include the presence of antibodies to the internal factor or to parietal cells in the blood serum (diagnosed in 50% of cases).

When detecting a pregnant cytopenia with a high or normal color index, it is necessary to perform a bone marrow puncture. In the myelogram, signs of megaloblastic anemia are revealed.

[12], [13], [14], [15],

Treatment of B12-deficiency anemia in pregnancy

Treatment consists in the appointment of cyanocobalamin 1000 μg intramuscularly once a week for 5-6 weeks. In severe cases, the dose may be increased.

A lot of vitamin B _{12 is} found in meat, eggs, cheese, milk, liver, kidneys, which should be taken into account in the prevention.

In the case of helminthic invasion, deworming is prescribed.

In all cases, the deficiency of vitamin B _12, its application leads to rapid and sustained remission.

Folic deficiency anemia in pregnancy

Anemia associated with a deficiency of folic acid is accompanied by the appearance of megaloblasts in the bone marrow, intracranial erosion of erythrocaryocytes, pancytopenia, macroditosis and hyperchromia of erythrocytes.

[16], [17], [18]

Causes of folic deficiency anemia in pregnancy

The reason for the development of folic acid deficiency anemia may be an increase in the need for folic acid during pregnancy 2.5-3 times, that is, more than 0.6-0.8 mg / day.

The risk factors for the development of folic deficiency anemia in pregnancy include hemolysis of various genesis, multiple pregnancy, prolonged use of anticonvulsants, and the state after resection of a significant part of the small intestine.

Folic acid, together with vitamin B, is involved in the synthesis of pyridine, glutamic acid, purine and pyrimidine bases necessary for the formation of DNA.

[19],

Symptoms of folic deficiency anemia in pregnancy

Deficiency of folic acid is manifested by signs of anemic hypoxia (general weakness, dizziness, etc.) and symptoms similar to those with B deficiency anemia. There are no signs of atrophic gastritis with achillia, funicular myelosis, hemorrhagic diathesis. Functional signs of CNS involvement were expressed. Diagnostics. Folic acid deficiency is characterized by the appearance of macrocytosis in the peripheral blood, hyperchromic anemia with anisocytosis and a reduced amount of reticulocytes, thrombocytopenia and leukopenia, and the presence of megaloblasts in the bone marrow. There is a deficiency of folic acid in the serum and especially in erythrocytes.

Treatment of folic deficiency anemia in pregnancy

Treatment is carried out with folic acid preparations at a dose of 1-5 mg / day for 4-6 weeks. Before the onset of remission. In the future, in case of non-elimination of the cause, prescribe maintenance therapy with folic acid preparations at a dose of 1 mg / day.

The dose of folic acid is increased to 3-5 mg / day throughout pregnancy, provided that you always take anticonvulsants or other antifolia agents (sulfasalazine, triamterene, zidovudine, etc.).

Prevention of folic deficiency anemia in pregnancy

Additional intake of folic acid in a dose of 0.4 mg / day is recommended for all pregnant women, starting from early terms. This reduces the incidence of folate deficiency and the occurrence of anemia and does not adversely affect the course of pregnancy, childbirth, the condition of the fetus and the newborn.

The intake of folic acid by women in the preconception period and in the first trimester of pregnancy helps to reduce the frequency of congenital anomalies in the development of the fetal CNS by 3.5 times in comparison with general population indicators. Admission of folic acid, which begins after 7 weeks of pregnancy, does not affect the frequency of neural tube defects.

It is necessary to consume enough fruits and vegetables rich in folic acid (spinach, asparagus, lettuce, cabbage, including broccoli, potatoes, melons), in raw form, as during the heat treatment most of the folates are lost.

Thalassemia in Pregnancy

Thalassemia is a group of hereditarily conditioned (autosomal dominant type) hemolytic anemia, characterized by a disruption in the synthesis of the alpha or beta chain of the hemoglobin molecule and thereby a decrease in the synthesis of hemoglobin A. In Ukraine it is extremely rare.

In thalassemia, one of the globin chains is synthesized in small amounts. The chain, which is formed in excess, aggregates and is deposited in erythrocaryocytes.

Clinical picture and treatment

Patients exhibit pronounced or. Insignificant gshtohromiya anemia, and the content of iron in the serum is normal or slightly elevated.

With mild form of alpha-thalassemia, pregnancy proceeds without complications, treatment is not performed. Heavy forms require the prescription of iron preparations re os, often transfusions of the erythroditic mass.

The special form of alpha-thalassemia, which occurs when all four "-globin genes are mutated, almost always leads to the development of fetal dropsy and its intrauterine death. This form is associated with a high frequency of preeclampsia.

If alpha thalassemia accompanies splenomegaly, delivery is performed by caesarean section, in all other cases - through natural birth canals.

Light forms of beta-thalassemia, as a rule, do not interfere with pregnancy, which occurs without complications. Treatment consists in the administration of folic acid, occasionally there is a need for transfusion of erythrocyte mass. Patients with severe form of beta-thalassemia do not live to reproductive age.

[20], [21], [22], [23], [24], [25]

Hemolytic anemia in pregnancy

Hemolytic anemia is caused by increased destruction of erythrocytes, which is not compensated by the activation of erythropoiesis. These include sickle cell anemia, which is a hereditarily caused structural abnormality of the beta chain of the hemoglobin molecule, hereditary microspherocytosis as an abnormality of the structural protein of erythrocyte membranes, that is, spectra, anemia caused by congenital enzymatic disorders, more often deficiency of erythrocyte glucose-6-phosphate dehydrogenase,

Clinical picture of this type of anemia is formed by common anemia symptoms and (pallor, general weakness, shortness of breath, signs of myocardial dystrophy), hemolytic jaundice (icterus, enlarged liver, spleen, dark urine and feces), intravascular hemolysis (hemoglobinuria, black urine, thrombotic complications), as well as an increased tendency to the formation of gallstones, associated with a high bilirubin content, in severe cases - hemolytic crises.

Pregnant women with hemolytic anemia in all cases need the qualified management of a hematologist. Decisions regarding the possibility of gestation, the nature of the treatment, the term and the method of delivery are made by the hematologist. The appointment of iron preparations is contraindicated.

Aplastic anemia in pregnant women

Allestic anemia is a group of pathological conditions accompanied by pancytopenia and a decrease in hematopoiesis in the bone marrow

In the pathogenesis, the following mechanisms are distinguished: a decrease in the number of stem cells or their internal defect, a disturbance in the microenvironment, leading to a change in the function of stem cells, immune suppression of the bone marrow, a defect or deficiency of the growth factors, external influences that disrupt the normal function of the stem cell.

It is extremely rare in pregnant women. In most cases, the cause is unknown.

Leading place is given to anemic syndrome (anemic hypoxia syndrome), thrombocytopenia (bruising, bleeding, menorrhagia, petechial rash) and as a consequence of neutropenia (purulent inflammatory diseases).

Diagnosis is carried out according to the results of a morphological examination of the punctate of the bone marrow.

Pregnancy is contraindicated and must be interrupted both in the early and late term. In the case of development of aplastic anemia after 22 weeks. Preterm delivery is indicated.

Patients constitute a high-risk group for hemorrhagic and septic complications. High maternal mortality, frequent cases of antenatal fetal death.

[26], [27], [28]

Classification of anemia in pregnancy

On etiology (WHO, 1992).

• Anemias associated with diet
  • iron deficiency (D50);
  • B12-deficient (D51);
  • folic deficiency (D52);
  • other related to nutrition (D53).
• Hemolytic anemia:
  • due to enzymatic disorders (D55);
  • thalassemia (D56);
  • sickle-shaped disorders (D57);
  • other hereditary hemolytic anemia (058);
  • hereditary hemolytic anemia (D59).
• Aplastic anemia
  • hereditary red cell aplasia (erythroblastopenia) (D60);
  • other aplastic anemia (D61);
  • acute posthemorrhagic anemia (D62).
• Anemia in chronic diseases (D63):
  • neoplasms (D63.0);
  • other chronic diseases (D63.8).
• Other anemia (D64).

By severity

Degree of geyzeggy	Concentration of hemoglobin, g / l	Hematocrit,%
Lightweight	109-90	37-31
Average	89-70	30-24
Heavy	69-40	23-13
Extremely heavy	<40	<13

In most cases, iron deficiency anemia develops in women (90%), and in half the cases there is a combined iron and folic deficiency genesis.

Other types of anemia in pregnant women are extremely rare.

[29], [30],

Adverse effects of anemia in pregnancy

Among specialists, the prevailing view is that anemia of any nature, especially pronounced and / or long-term, has an adverse effect on the health of the mother and fetus. According to WHO (2001), anemia and iron deficiency in pregnant women are associated with an increase in maternal and perinatal mortality and an increase in the frequency of preterm delivery. Anemia can be the cause of the birth of small children, which causes an increase in the morbidity and mortality of newborns, the prolongation of labor and an increase in the frequency of surgical interventions in childbirth.

The results of the meta-analysis of data on the effect of anemia on the course of pregnancy and its outcome indicate that adverse effects depend not only on anemia, but also on many other factors that are difficult to take into account and which in turn can be caused by anemia.

It is generally accepted that severe anemia (Hb <70 g / L) adversely affects the condition of the mother and fetus, leads to impairment of the function of the nervous, cardiovascular, immune and other body systems, an increase in the frequency of preterm labor, postpartum infectious-inflammatory diseases, intrauterine growth retardation, neonatal asphyxia and birth trauma.

The data of evidence-based medicine determine the need for effective prevention and treatment of this complication of pregnancy.

[31]