ANEMIAS DURING PREGNANCY
By
Osama M. Warda, MD
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http://www.ups7.com/en/file/6154/ANEMIAS-DURING-PREGNANCY-pdf.htmlDefinition:
Anemia means reduction below normal of either red blood cells (RBCs) count, or hemoglobin percentage, or both leading to deficient oxygen carrying capacity of the blood.
During pregnancy; anemia is diagnosed if:
RBCs count is less than 3.5 millions/ cc OR,
Hemoglobin content less than 10 gm/dL , or
Hematocrit value is less than 30 %
Incidence:
- Anemia is the most common medical complication in pregnancy. More than 50% of all pregnant women in the USA (and much more numbers in the developing countries including Egypt) suffer anemia during pregnancy.
- Iron deficiency anemia is the most common type, followed by blood loss due to obstetric cause, and anemia due to chronic infection (see later under classification of anemia).
Anemia Pregnancy Inter-relations:
A]. Effect of anemia on pregnancy ( mother & fetus):
1- Increased incidence of Preeclampsia-eclampsia, especially with iron deficiency anemia and megaloblastic anemia (mechanism unknown).
2- Increased incidence of placental abruption (accidental hemorrhage).
3- Increased incidence of stillbirths, and neonatal deaths.
4- Increased incidence of preterm labor.
B]. Effect of pregnancy anemia:
Aggravation of the pre-existing anemia occurs due to;
1- Expansion of the maternal plasma volume (see physiologic changes due to pregnancy).
2- Fetal utilization of substrates necessary for building up of hemoglobin molecules.
Note Box ( )
Anemia of pregnancy (hyderemia; hemodilution):In pregnancy, a woman's blood volume increases by as much as 50 percent. This causes the concentration of red blood cells in her body to become diluted. This is sometimes called anemia of pregnancy and is not considered abnormal unless the levels fall too low.
Classification (types) of Anemia:
The simplest, yet effective, method of classifying anemia is according to the alteration of the blood indices, accordingly anemia may be hypochromic microcytic ( reduced indices), hyperchromic macrocytic ( increased indices), or normochromic normocytic ( un-altered indices).
[I]. HYPO-CHROMIC MICRO-CYTIC ANEMIA:
1- Iron deficiency anemia (most common).
2- Thalassemia (certain types).
3- Chronic infections (eg . glomerulonephritis, pyelonephritis).
4- Chronic lead poisoning.
5- Vitamin B6 deficiency.
[II].HYPER-CHROMIC MACRO-CYTIC ANEMIA:
1- Folic acid deficiency anemia.
2- Vitamin B12 deficiency anemia.
[III]. NORMOCHROMIC NORMOCYTIC ANEMIA:
1- Hemorrhagic anemia (due to blood loss).
2- Hemolytic anemias; (a) thalassemia, (b) sickle cell anemia, (c) spherocytosis, and (d) G6PD deficiency (= glucose-6-phosphate dehydrogenase deficiency)
3- Hypoplastic (aplastic) anemia.
IRON DEFICIENCY ANEMIA
It is the most common type of anemia encountered during pregnancy.
Physiological Role of iron during pregnancy:
Enters the haem portion of hemoglobin & myohemoglobin.
Respiratory enzymes as cytochrome oxidase enzyme.
Placental enzymes
Fetal hematopoeisis.
Metabolism of iron during pregnancy:
Normal diet supplies 14 mg of iron per day.
Only 1-2 mg ( 10-15% of dietary iron) is absorbed depending on iron stores (ferritin-apoferritin system).
Iron is absorbed in the 'ferrous' state in the presence of vitamin C. Phytate & phosphate decrease iron absorption .
Haem iron of red meat & liver is rapidly absorbed than vegetable iron in apple, spinache, and other vegetables.
Daily requirement of iron during pregnancy:
The daily requirement of the pregnant lady is 4 mg of elemental iron (it is 1mg for adult male, 2mg for the adult non-pregnant female).The total requirement during pregnancy is about 1000 mg of elemental iron calculated by the Council on Food and Nutrition as follows;
Þ To compensate for external iron loss…….= 170 mg
Þ To allow expansion of maternal cell……..= 450 mg
Þ Iron for fetal needs ………………………. =270 mg
Þ Iron in placenta and cord ………………….= 90 mg
Etiology of iron deficiency anemia during pregnancy:
[A]. Decrease intake of iron:
1. Poor diet.
2. Extensive morning sickness
[B]. Diminished absorption of iron:
1. Lack of vitamin C and proteins.
2. Increased phosphate & phytates.
3. Decreased gastric acidity & use of antacids.
4. Malabsorption syndromes, and parasitic infestations.
[C]. Increased iron demands during pregnancy:
1. Multiple pregnancy
2. Hemorrhage with pregnancy
3. Multi-parity
Clinical Picture:
S y m p t o m s:
1. General; pallor, tiredness, easy fatigability.
2. Cardiovascular; Dyspnea on exertion, palpitation, angina pains, swelling of lower limbs, and other low cardiac output symptoms.
3. Gastrointestinal; anorexia, nausea, vomiting, constipation.
4. Nervous System; lack of concentration, numbness and tingling, headaches.
S i g n s:
1. General; pallor, glassy tongue, brittle nails
2. Cardiovascular; haemic murmurs over the procordium on auscultation.
Investigations:
[A]. Peripheral blood ( complete blood count; CBC):
Findings suggestive of diagnosis include;
Microcytic hypochromic anemia ( ie, reduced indiced)
Anisocytosis (ie, different sizes of RBCs)
Piklocytosis (ie, different shapes of RBCs)
Normal reticulocytic count (ie, 0.5%- 1.5%)
Normal platelet & leukocyte counts
[B]. Blood chemistry:
Findings suggestive of diagnosis include;
Decreased serum iron less than 60µg/ dl (normal 90-150 µg / dl)
Decreased serum ferritin
Increased serum iron binding capacity more than 300 µg%
Increased free erythrocyte proto-porphyrin.
[C]. Bone marrow biopsy (seldom done):
There is absence of stainable iron in bone marrow.
Treatment of iron deficiency anemia during pregnancy:
[A]. Prophylactic Treatment:
Good pre-pregnancy nutrition not only helps prevent anemia, but also helps build other nutritional stores in the mother's body. Eating a healthy and balanced diet during pregnancy helps maintain the levels of iron and other important nutrients needed for the health of the mother and growing baby.
Every pregnant woman needs iron supplementation during pregnancy; the earlier the better ( but NOT earlier than 14 weeks pregnancy)
Oral iron supplementation to ALL pregnant ladies after 16 weeks gestation as 60-80 mg of elemental iron per day; can be obtained from;
Þ 200 mg ferrous fumarate, OR
Þ 300 mg ferrous sulfate, OR
Þ 550 mg ferrous gluconate, PLUS
Þ 1000mg vitamin C ( to help absorption) and 2mg folic acid (to help hematopoeisis). Antacids lower the absorption of iron from the stomach. [See appendix I ]
[B]. Active Treatment:
Active management of anemia depends on 2 main factors; severity of anemia, and the duration of pregnancy.
(1). Pregnancy 16-30 weeks: Oral ferrous sulfate 300mg t.d.s (ie, 900mg per day, or triple the prophylactic dose). This treatment is supposed to increase the hemoglobin concentration by 1 gm per month.
(2). Pregnancy after 30 weeks with severe anemia: parenteral iron therapy is indicated. Iron preparation can be given via intramuscular injection (eg, iron sorbitol; imferon®: 250mg every other day) or intravenous infusion in a crystalloid solution (eg ferrous succinate; ferosac®: 1amp in 100 ml of dextrose 5% every other day). [See appendix II]
Side –effects of iron therapy:
- Oral iron preparations may cause gastric upsets, constipation, dark green or black stools
- Parenteral iron preparations may cause pain & staining at the site of injection, hemosiderosis, and also anaphylaxis.
(3). Anemia after 35 weeks pregnancy and hemoglobin less than 6 gm/dl:
These patients should receive transfusion of packed RBCs (or whole blood if packed RBCs are not available). However, transfusions carry the hazards of transmission of viral infection, and transfusion reactions.
Folic Acid Deficiency Anemia
Folic acid deficiency causes megaloblastic anemia which is uncommon type of anemia during pregnancy accounts for 3% of cases of anemia during pregnancy.
Folic acid metabolism during pregnancy:
Pregnancy is associated with negative folate balance.
Folic acid & iron play a central role in nutrition & DNA synthesis.
Folic acid is reduced by reductase enzyme, giving dihydrofolic acid, which is further reduced by the same enzyme giving tetrahydrofolic acid (ie, folinic acid).
Folinic acid is necessary for DNA synthesis, cell growth, cell division, epithelial cells, and bone marrow cells.
Folate requirements are increased during pregnancy for the growing fetus, placenta, maternal RBCs, and uterine hypertrophy. Folate requirement in normal pregnant lady are 200-300 µg/ day.
Etiology of folic acid deficiency anemia:
The causes are the same as those of iron deficiency anemia (see before), plus the following:
Anti-convulsion therapy (eg, pregnant epileptic patient on epanutin®).
Antipyretic therapy.
Chronic hemolysis.
Investigations for folate deficiency:
[A]. Peripheral blood:
The findings suggestive of diagnosis:
· Macrocytic hyperchromic anemia (MCV increased)
· Hypersegmented polymorphs
· Elevated reticulocytic count.
[B]. Blood chemistry:
Decreased plasma folate level; the finding of a serum folate <2ng/> 2%)
Elevated indirect serum bilirubin.
Shortened life span of RBCs (by isotope chromium 51).
Erythroid hyperplasia of the bone marrow.
Hemoglobinopathies
Introduction:
Hemoglobin molecule is formed of 2 parts; haem which is an iron containing porphyrin, and globin which is a protein formed of 2 pairs of polypeptide chains (in the adult hemoglobin they are 2 α chains and 2β chains). Genes responsible for α chains are carried on chromosome 16, while those responsible for β chains on chromosome 11.Abnormalities in synthesis of either chain is genetically determined and result in thalassemia which are causes of anemia. On the other hand, in sickle-cell hemoglobinopathies, the polypeptide chains of hemoglobin are normal except for the amino acid sequence which is abnormal with replacement of glutamic acid by valine at the 6th position leading to formation of hemoglobin- S which is abnormal.
Thalassemias:
§ There are 2 main forms of thalassemia namely; the α- thalassemia due to inadequate synthesis of the α-chains, and the β- thalassemia due to inadequate synthesis of the β-chains.
§ Thalassemias are genitically determined & inherited as autosomal recessive.
§ Thalassemias are found throughout the world but centered in the Mediterranean are, Middle East, South-east Asia, and in India.
§ The clinical varieties of α- thalassemia are variable from lethal form (not compatible with extra-uterine life and causes hydropes fetalis to the affected fetus), to sub-clinical carrier types. The milder forms can be encountered in the pregnant lady with anemia.
§ Beta –thalassemias are either major (when the deficiency of the β-chain is homozygos), or minor (when the deficiency of the β-chain is heteozygos). Only the minor types can be encountered in the pregnant woman.
Management of pregnancies complicated by thalassemias:
[A]. MATERNAL: (with the aid of a hematologist)
No specific therapy for β-thalassemia minor during pregnancy; as the outcome for both the mother & the fetus is satisfactory.
Blood transfusion is rarely indicated except for hemorrhage.
Prophylactic folic acid supplementation is strongly indicated.
Proper treatment of infections.
Iron chelating agents (eg, Desferal®) are indicated.
[B]. FETAL:
The fetal management in patients with thalassemia or sickle cell disease is concerned with the fetal risk of acquiring the disease. Management consists of:
Genetic counseling to determine the fetal risks by Mendelian laws.
Antenatal diagnosis of thalassemias & sickle cell anemia may be achieve via one of the following techniques:
(a) Chorionic villus sampling,
(b) Early amniocentesis between 7-11 weeks gestation,
(c) Cordocentesis through percutaneous umbilical blood sampling (PCUBS), or
(d) Fetoscopy with cord blood sampling.
3. Termination of pregnancy is considered if the fetus is severely affected.
4. Reassurance of pregnancies if the fetus is not affected or mildly affected.
Sickle-cell Hemoglobinopathies:
Again the abnormality here is the replacement of the glutamic acid by valine at the position 6 on the polypeptide chain of hemoglobin leading to formation of hemoglobin-S.
Sickle-cell disease is inherited as autosomal recessive ( as thalassemia).
There are 4 types; sickle cell anemia (SS-disease), sickle-cell trait (SA-disease), sickle cell- hemoglobin C disease (SC-disease), and sickle cell - β-thalassemia disease (SB-disease). All (except the first type) are mild forms with no significant maternal complications.
Sickle-cell anemia (SS-disease) and pregnancy:
Incidence:
Sickle –cell anemia is common among black races. The theoretical incidence during pregnancy is 1:600 pregnancies. However it seems to be not so common due to high death rates among children with the disease, and lower parity of women with the SS- disease.This disease is almost unknown among Egyptian pregnant women.
Effect of sickle cell anemia on pregnancy, delivery, and puerperium:
It has a very bad outcome for both the mother and the fetus
[A]. MATERNAL:
Maternal mortality is 6% due to the following complications:
1. Severe anemia.
2. Sickle cell crisis; including hemolytic crisis, sequestration crisis, aplastic crisis, and thrombotic crisis.
3. Infections; pulmonary infections with pneumonia, chest infections, and urinary tract infections.
[B]. FETAL:
Bad as about 50% of pregnancies end by abortion, stillbirth, low birth weight infants, or neonatal deaths.
Management of pregnancies complicated by the SS-disease:
[A]. PREGNANCY:
Very close observation (frequent antenatal visits, or hospital admissions).
Folic acid supplementation ( 2mg orally / day).
Eradication of asymptomatic bacteruria & pyelonephritis.
Guard against pneumonia and heart failure.
Prophylactic blood transfusion.
Management of crisis by:
a) Oxygenation
b) Hydration (iv fluid therapy)
c) Blood transfusion
d) Heparinization for the thrombotic cricis
[B]. DELIVERY: (managed as cardiac patients)
Comfortable but not sedated.
Blood ready for transfusion.
Vaginal delivery is preferred, and CS for obstetrical indication only.
Regional anesthesia is better than general anesthesia.
Replace blood loss adequately.
[C]. CONTRACEPTION:
Tubal sterilization is indicated even if the parity is very low.
Combined oral contraceptives are contraindicated (↑thrombosis)
Intrauterine contraceptive device (IUCD) is contraindicated (↑infection).
APPENDIX ( I ):
Iron-containing foods:
Good food sources of iron include the following:
meats - beef, lamb, liver, and other organ meats
poultry - chicken, duck, turkey, liver (especially dark meat)
fish - shellfish, including clams, mussels, oysters, sardines, and anchovies
leafy greens of the cabbage family, such as broccoli, kale, turnip greens, and collards
legumes, such as lima beans and green peas; dry beans and peas, such as pinto beans, black-eyed peas, and canned baked beans
yeast-leavened whole-wheat bread and rolls
iron-enriched white bread, pasta, rice, and cereals
