Anemia of Pregnancy | Medical Science Optional Notes for UPSC PDF Download

Anemia of pregnancy-Causes

Acquired Causes of Anemia During Pregnancy:

• Iron deficiency anemia
• Anemia resulting from acute blood loss
• Anemia associated with inflammation or malignancy
• Megaloblastic anemia
• Acquired hemolytic anemia
• Aplastic or hypoplastic anemia

Hereditary Causes of Anemia During Pregnancy:

• Thalassemias
• Sickle-cell hemoglobinopathies
• Other hemoglobinopathies
• Hereditary hemolytic anemias

Additionally, dimorphic anemia refers to a condition characterized by two deficiencies—iron-deficiency and nutritional macrocytic anemia.

Physiological Anemia of Pregnancy

Hematological Changes During Pregnancy

• Pregnancy-Induced Hypervolemia: Blood volume expansion occurs due to an increase in both plasma and erythrocytes.
• Red Cell Volume:
  • While more plasma than erythrocytes is typically added to the maternal circulation, there is a substantial increase in erythrocyte volume, averaging 450 mL.
  • The peak increase in red cell volume occurs early in the third trimester, corresponding to the period of maximal erythrocyte production.
• Plasma Volume:
  • By 12 menstrual weeks, plasma volume expands by approximately 15 percent compared to the prepregnancy state.
  • Maternal blood volume experiences its most rapid expansion during the second trimester.
  • It averages 40 to 45 percent above the nonpregnant blood volume after 32 to 34 weeks of gestation.

Hemoglobin and Hematocrit (Decreases)

• Physiological Anemia During Pregnancy:
  • There is a normal physiological anemia that occurs during pregnancy.
  • This anemia is attributed to the significant increase in plasma volume (30-40%), surpassing the increase in red cell mass (20-30%). This leads to hemodilution, resulting in an apparent decrease in hemoglobin levels.
• Anemia Criteria in Pregnancy:
  • Anemia is considered to occur when the hemoglobin (Hb) level is less than 11 g/dL during pregnancy.
• ICMR Classification of Anemia in India:
  • The Indian Council of Medical Research (ICMR) has a classification of anemia based on Indian standards.
  • Notable differences in this classification include the inclusion of "Very Severe Anemia" when Hb is less than 4g%.
  • Second-trimester anemia is graded when Hb is less than 11 g%.
• Total Additional Iron Requirement During Pregnancy and Its Distribution:
  • The average iron stores in a non-pregnant female amount to approximately 300 mg.
  • However, during pregnancy, the requirement for iron significantly increases to 1000 mg.
  • Iron supplementation is crucial to prevent iron deficiency anemia in pregnant women, forming the basis for prophylactic iron supplementation during pregnancy.
  • In a typical singleton gestation:
    • Maternal iron needs average around 1000 mg.
    • Of this, 300 mg is allocated for the fetus and placenta, 500 mg for maternal hemoglobin mass expansion, and 200 mg is naturally shed through the gut, urine, and skin.
  • The total iron needs, slightly exceeding 1000 mg, are concentrated in the last two trimesters of pregnancy.
  • This amount equates to about 6 mg of iron absorbed per day in a woman with minimal or absent storage iron at the beginning of pregnancy.
  • Accumulating this significant amount of iron over a 6-month period is noteworthy, especially when considering the average total body iron content of 2,200 mg and the 1.3 mg of iron absorbed per day by non-pregnant women.

Post Partum iron stores

• While 450 mg of iron is necessary for red cell production during pregnancy, a significant portion of this can contribute to augmenting iron stores after a vaginal delivery, particularly when the red cell mass decreases postpartum.
• This scenario is akin to a postpartum iron injection, leading to a spontaneous increase in serum ferritin levels within a few months after delivery. This is particularly applicable to women who developed mild iron deficiency during late pregnancy due to the iron released by the decline in red cell mass.
• Postpartum iron status sees improvement due to reduced iron loss during this period. Human milk accounts for less than 0.3 mg/day of iron loss, and menstruation is infrequent in women during the initial months of lactation.
• The average blood loss during a cesarean delivery is almost double that observed in the average vaginal delivery of a single fetus. Consequently, the postpartum improvement in iron status may be less complete after a cesarean delivery.

Explain why new born infant of a severely anemic mother does not suffer from iron deficiency anemia?

• A noticeable decrease in hemoglobin concentration is a common manifestation of iron deficiency.
• During the third trimester of pregnancy, there is a heightened requirement for extra iron to enhance maternal hemoglobin levels and facilitate transportation to the fetus.
• Interestingly, despite the severity of maternal iron deficiency, the amount of iron directed to the fetus remains similar in both normal and iron-deficient mothers. As a result, the newborn infant of a severely anemic mother does not experience iron deficiency anemia.

Anemia of Pregnancy

Clinical Features of Anemia during Pregnancy

The key signs and symptoms associated with iron deficiency anemia in pregnancy can be succinctly described as follows:

• Fatigue
• Low Physical and Mental Capacity
• Headache
• Vertigo
• Leg Cramps
• Pagophagia (craving for ice)
• Cold Intolerance
• Koilonychias (spoon-shaped nails)
• Mucosal Paleness
• Angular Stomatitis

Diagnosis of Iron Deficiency Anemia in Pregnancy - Investigations:

• Hemoglobin (Low)
• Hematocrit (Low)
• Red Cell Indices (MCV, MCH, MCHC, RDW)
• Peripheral Smear (Morphological changes include erythrocyte hypochromia and microcytosis. A careful examination is conducted to rule out sickle cell anemia, especially in individuals of African origin.)
• Serum Iron (Low)
• Serum Ferritin Levels (Confirmation of diagnosis when < 10-15 mg/L)
• Serum Transferrin (Low)
• TIBC (Total Iron-Binding Capacity - Raised)

Diagnosis-Iron deficiency anemia in Pregnancy

Diagnosis-Iron deficiency anemia in Pregnancy 

Newer RBC parameters for IDA

Role of Serum Ferritin

• The gold standard for assessing iron stores is bone marrow staining, but it is invasive and impractical during pregnancy.
• A more sensitive and specific marker for iron deficiency is serum ferritin.
• Given that non-anemic iron deficiency (NAID) can impact feto-maternal outcomes, many obstetricians and hematologists suggest a cutoff of 30 pg/dl for diagnosing and treating iron deficiency during pregnancy.
• Currently, low serum ferritin values are considered the most reliable confirmation of iron deficiency in pregnancy.

Consequences of Iron deficiency anemia in Pregnancy

Treatment-Iron deficiency anemia in Pregnancy

• Regardless of anemia status, daily oral supplementation with 30 to 60 mg of elemental iron and 400 μg of folic acid is recommended in pregnancy. 
• Anemia resolution and restitution of iron stores can be accomplished with simple iron compounds - ferrous sulfate, fumarate, or gluconate—that provide about 200 mg daily of elemental iron.

Role of Deworming in prevention of IDA

WHO recommends routine deworming using single dose Albendazole (400 mg) or mebendazole (500 mg) in all pregnant patients after first trimester in areas where both

• Baseline prevalence of hookworm/Trichuris Trichura infection is > 20%
• Prevalence of anemia in pregnant women is > 40% and is therefore applicable to India.

Management Algorithm for IDA in Pregnancy

The mode of repletion of iron stores in IDA of pregnancy is guided by the severity of anemia, the stage of pregnancy, obstetric risks of hemorrhage (e.g. premature labor, placenta praevia) and non-obstetric maternal comorbidities (hemoglobinopathy, chronic disease etc.).

Modes of Iron Supplementation

• For optimal absorption, pregnant women are advised to take oral iron on an empty stomach or 1 hour after meals, preferably with a vitamin C-rich product such as orange juice or guava.
• Ferric salts (III) generally offer better gastrointestinal (GI) tolerability than Ferrous (II) salts but come with the trade-off of reduced iron absorption.
• Intramuscular (IM) iron supplementation, specifically Low Molecular Weight Iron Dextran, is recommended by the Ministry of Health and Family Welfare (MoHFW) guidelines for treating moderate anemia in pregnancy. However, the intramuscular route has largely been replaced by the intravenous route due to issues like painful injections, skin discoloration, and the risk of side effects at most centers.
• Intravenous (IV) iron has advantages such as complete bioavailability, fewer GI side effects, and faster recovery of hemoglobin compared to oral iron. Patients should be informed about transient side effects like nausea, vomiting, pruritus, headache, flushing, myalgia, arthralgia, back pain, and chest pain, which typically resolve within 48 hours of infusion.
• Dose calculation follows Ganzoni's equation: Required Iron dose (mg) = (2.4 × D(target Hb - actual Hb) × prepregnancy weight in kg) + 1000 mg for replenishment of stores.
• After achieving a normal hemoglobin range, 100-200 mg/day of iron should continue for at least 3 months and at least 6 weeks postpartum to replenish stores. Additionally, 60-100 mg/day of oral iron should continue for at least 3-6 months postpartum.

Indications and Contraindications of IV Iron in Pregnancy

Management of Megaloblastic anemia

Management of Folic Acid Deficiency Anemia

• Folic acid supplementation is the primary treatment along with a nutritious diet.
• Oral administration of folic acid once daily shows a significant improvement in blood parameters.
• Reticulocyte count increases and issues like leukopenia and thrombocytopenia are corrected within four weeks of starting folic acid treatment.

Prevention Recommendations by WHO

• All women attempting conception until 12 weeks of pregnancy are advised to take a 400 mcg folic acid supplement daily.
• Women with a history of a fetus affected by neural tube defects or those who've had a baby with this condition should:
  • Receive information about the risk of recurrence.
  • Be informed about the protective effect of folic acid supplementation before conception.
  • Consider higher-dose supplementation (5 mg as per WHO or 4 mg according to Williams Obstetrics).
  • Increase their intake of folate-rich foods.

Vitamin B12 Deficiency during Pregnancy

• Megaloblastic anemia due to vitamin B12 deficiency is uncommon during pregnancy.
• Causes include total gastrectomy requiring 1000 mcg intramuscularly per month and partial gastrectomy.
• Individuals with partial gastrectomy might not require supplementation if serum vitamin B12 levels are sufficient.
• Other causes involve conditions like Crohn's disease, ileal resection, and bacterial overgrowth in the small bowel.

These guidelines emphasize the importance of folic acid supplementation for women planning to conceive or during the early stages of pregnancy, along with addressing vitamin B12 deficiency causes during pregnancy.

Anemia of pregnancy-Repeats

Q1: Describe the causes of anemia in pregnancy. How would you manage a case of dimorphic anemia in Pregnancy? (2006)

Q2: (i) What is physiological anemia of pregnancy?
(ii) Do all pregnant women need additional iron? Explain in brief
(iii) What is the diagnostic test of iron deficiency anemia in pregnancy and why?
(iv) How much total additional iron is required during pregnancy and what is the distribution in the mother's body? (2019) (4+4+6+6 = 20)