During pregnancy, the total blood volume normally increases 40%, reaching a maximum of about 5 liters.

This 40% increase is accompanied by a smaller increase (about 33%) in the red cell mass. Because the red cell mass doesn’t quite keep up with the total blood volume, there is a naturally-occurring decrease in both the hemoglobin and the hematocrit.

• The hemoglobin can normally dip to 5 grams
• The hematocrit can normally dip to 33%

This normal physiologic event is sometimes called a physiologic anemia of pregnancy, or a dilutional anemia of pregnancy. It is an expected, non-pathologic event.

That said, true anemia during pregnancy is a relatively common event, being caused by a collection of nutritional, genetic, and medical issues. True anemia during pregnancy is usually defined as:

• Hemoglobin less than 0 grams
• Hematocrit less than 30 %

Iron Deficiency

Of the anemias seen during pregnancy, iron deficiency is the most common, representing about 90% of all anemias in the North American population.

In the event of iron deficiency anemia, a peripheral blood smear will typically demonstrate the classical finding of a microcytic, hypochromic anemia, in other words, a low mean corpuscular volume, and a low mean corpuscular hemoglobin, small, pale red cells.

Other associated laboratory findings include a low total serum iron, a low serum ferritin, and an increased total iron binding capacity.

A number of causes of iron-deficiency during pregnancy can be listed, but the more common are:

1. Nutritional deficiencies of iron and/or folate
2. Chronic blood loss
3. Hemolysis
4. Intestinal helminth infection

In the case of mild iron-deficiency anemia during pregnancy, the consequences, if any, are difficult to quantify. But for the more severe iron deficiencies, with hemoglobin values of 7 or less, there are significant risks of oligohydramnios, abnormal fetal heart rate tracings, prematurity, fetal growth restriction, and maternal mortality.

The diagnosis of iron deficiency anemia during pregnancy is usually made following the first laboratory testing that includes a complete blood count.

Sometimes, the diagnosis is not made until a later blood draw, or if the patient becomes symptomatic with unusual amounts of fatigue, shortness of breath on exertion, or developing pallor.

The diagnosis is confirmed with a number of laboratory tests including:

• Complete blood count with peripheral smear, to document the severity of the anemia, and identify the degree of hypochromicity and microcytosis
• Reticulocyte count, to confirm the bone marrows ability to respond to the low hemoglobin
• Serum iron, which is expected to be low
• Serum TIBC, which is expected to be elevated, reflecting the body’s attempts to maintain homeostasis
• Serum ferritin, a somewhat more reliable reflection of the body’s iron stores

Some physicians, when dealing with mild degrees of anemia during pregnancy, will presume iron deficiency to be present, and go directly to a therapeutic trial of oral iron supplementation. A prompt response is then considered confirmatory of the diagnosis. A failed response would then prompt a detailed laboratory evaluation.

• Of course, should there be little response, one never knows whether this is due to patient non- compliance, incorrect diagnosis, ongoing loss, or multiple factors leading to anemia
• There are a few anemic women, for example, some of those with sickle cell disease, who should not be taking extra iron, as they already have too Attempting a therapeutic trial of iron in these patients will not only postpone an accurate diagnosis, but will also add to their iron load.

Because iron deficiency is so commonly seen among pregnant women, we routinely give prenatal vitamin supplementation to all pregnant women, ideally starting at least 3 months prior to the pregnancy.

Each prenatal vitamin contains about 27 mg of elemental iron. This is sufficient to boost the oral intake of iron modestly, but is not enough iron to reverse more severe cases. In these cases, we prescribe oral iron supplements containing 60-65 mg of elemental iron.

These are ideally taken 3 times a day, but patient intolerance may dictate less frequent dosing. Even if taken once every other day, it is better than not taking it at all.

The intolerance is due to gastric distress, or constipation, or both. The best absorbed form of iron, ferrous sulfate, also causes the most side effects. The least well absorbed, ferrous fumarate, is the most well tolerated. So there are trade-offs in choosing the best oral preparation for this problem.

Injectable iron can also be given, but also has significant, but different, side effects, and is only infrequently necessary.

Folate Deficiency:

A less common cause of anemia is folic acid deficiency. This is caused by a number of problems, among them:

• Dietary deficiency (lack of leafy green vegetables)
• Alcoholism (interfering with absorption of folate)
• Intestinal disease, such as Crohn’s or tapeworm, diminishing digestion and absorption of folate
• Various medications, including phenytoin, triamterene, sulfasalazine, pyrimethamine, and trimethoprim-sulfamethoxazole

In contrast to the small, pale red cells of iron deficiency, the folate-deficient red cells are large and pale, called megaloblasts.

Folate deficiency during pregnancy has special significance beyond just making the patient anemic. It is associated with fetal neural tube defects, such as meningomyelocele. For that reason, 400 mcg of folic acid is included in all prenatal vitamins, and it is recommended that these vitamins be started several months prior to conception.

An additional 4 mg of folic acid is given in high risk settings, including:

• Women with a history of neural tube defects
• Multiple gestations
• Women taking anticonvulsant

Hemoglobinopathy

Another less common cause of anemia, particularly among some population subgroups, are the hemoglobinopathies. The two most prevalent of these in North America are:

• Sickle Cell Anemia, and
• Thalassemia

Screening for these conditions can be done among those at risk, for example, those of African or Mediterranean ancestry. But because of increasing ethnic mixing, reliance on ethnic heritage may prove ineffective in identifying all those with hemoglobinopathies.

Sickle Cell Trait is found in about 10% of African- Americans. It is a generally innocent carrier state with a combination of one strand of normal beta hemoglobin A, and one strand of the abnormal beta hemoglobin S. Sickle Cells trait is not particularly worrisome or dangerous during pregnancy, but has three important significances:

1. These women are somewhat more vulnerable to urinary tract
2. These women are somewhat protected against malaria (not so important if one lives in Chicago).
3. These women and their partners need genetic In the event both parents carry the Sickle Cell trait, then there is a one in four chance of their offspring having sickle cell disease, a pretty serious condition.

While less common, Sickle Cell Disease is a much more dangerous hemoglobinopathy, and frequently associated with anemia. The diagnosis is made through hemoglobin electrophoresis, although most pregnant patients with this conditional will already be aware they have the condition.

Pregnancy complications are increased, including:

• Abortion
• Stillbirth
• Neonatal Death
• Pre-eclampsia
• Growth restriction
• Infections of all types
• Thromboembolic events
• Acute chest syndrome
• Preterm labor
• Premature rupture of the membranes
• Preterm delivery
• Abruption
• Pulmonary hypertension

While these complications are common among these patients, it is also true that the majority of these patients will experience a good outcome. But because of the relatively high risk of bad outcome, they are best managed in high-risk centers, by teams of obstetricians, internists, hematologists, and geneticists skilled and experienced in managing these patients.

There are several key obstetrical management issues:

• Hydration is important to prevent pain and crises, so aggressive use of IV therapy and antinausea medication in the first trimester is undertaken.
• Many of these women are taking hydroxyurea and iron chelating agents, and current recommendations are to stop both during the pregnancy.
• Routine blood transfusion is not needed, but selective transfusions can be indicated in some high risk patients.
• Oral iron therapy is withheld, but large doses of folate (4 mg/day) are given.
• Watch for infections (urine, pulmonary)
• Serial fetal monitoring of both heart rate and ultrasound will be needed.
• Patients should undergo labor induction or cesarean section only for normal obstetrical indications.
• During labor, maintain oxygen saturation at > 95% at all times.

Thalassemia represents a spectrum of hemoglobinopathies, characterized by abnormal globin chain synthesis leading to abnormal hemoglobin. These are further categorized as major, intermediate, or minor in nature. Most are minor.

With beta thalassemia minor during pregnancy, the main problem is incorrectly labeling the hypochromic, microcytic anemia as an iron deficiency anemia, which will lead to the unncecessary prescription of iron to these patients. They do need extra folate, but they don’t need extra iron.

Beta thalassemia major usually results in infertility, so the occurrence of a pregnant woman with this problem would be quite rare, but definitely dangerous, cardiovascular overload and thrombosis being major risks.

Intermediate forms of thalassemia during pregnancy require little other than extra folate, avoidance of iron, and monitoring of maternal and fetal condition as the pregnancy advances.

For alpha thalassemia major, also known as Bart’s syndrome, there is a significant risk of fetal hydrops, so close monitoring of the fetus is necessary.