Normal values for concentrations of many cellular elements during pregnancy are listed in the Appendix (Serum and Blood Constituents). The Centers for Disease Control and Prevention (1998) defined anemia in iron-supplemented pregnant women using a cutoff of the 5th percentile—11 g/dL in the first and third trimesters, and 10.5 g/dL in the second trimester (Fig. 56-1). The modest fall in hemoglobin levels and hematocrit values during pregnancy is caused by a relatively greater expansion of plasma volume compared with the increase in red cell volume. The disproportion between the rates at which plasma and erythrocytes are added to the maternal circulation is greatest during the second trimester. Late in pregnancy, plasma expansion essentially ceases, while hemoglobin mass continues to accrue.
The causes of more common anemias encountered in pregnancy are listed in Table 56-1. Their frequency is dependent on multiple factors such as geography, ethnicity, socioeconomic level, nutrition, preexisting iron status, and prenatal iron supplementation (American College of Obstetricians and Gynecologists, 2017a). In the United States, the prevalence of anemia in pregnancy is 3 to 38 percent (Centers for Disease Control and Prevention, 1989). In Latin America and the Caribbean, anemia prevalence ranges from 5 to 45 percent among women of childbearing age (Mujica-Coopman, 2015). Rates are also high in Israel, China, India, South Asia, and Africa (Azulay, 2015; Kumar, 2013, Stevens, 2013). Figure 56-2 highlights the global trends in hemoglobin concentrations and anemia thresholds in pregnant and nonpregnant women.
TABLE 56-1Causes of Anemia During Pregnancy ||Download (.pdf) TABLE 56-1 Causes of Anemia During Pregnancy
Anemia caused by acute blood loss
Anemia of inflammation or malignancy
Acquired hemolytic anemia
Aplastic or hypoplastic anemia
Global trends in hemoglobin concentrations in pregnant and nonpregnant women. (Reproduced with permission from Stevens GA, Finucane MM, De-Regil LM, et al: Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data, Lancet Glob Health. 2013 Jul;1(1):e16–25.)
Effects on Pregnancy Outcomes
Most studies of anemia during pregnancy describe large populations and deal with nutritional anemias. Anemia is associated with several adverse pregnancy outcomes including preterm birth (Kidanto, 2009; Kumar, 2013; Rukuni, 2016). Children born to iron-deficient women and without iron supplementation are reported to have lower mental development scores (Drassinower, 2016; Tran, 2014).
A seemingly paradoxical finding is that healthy pregnant women with a higher hemoglobin concentration are also at greater risk for adverse perinatal outcomes (Murphy, 1986; von Tempelhoff, 2008). This may result from lower than average plasma volume expansion of pregnancy concurrent with normal red cell mass accrual. Scanlon and associates (2000) studied the relationship between maternal hemoglobin levels and rates of preterm or growth-restricted newborns in 173,031 pregnancies. Women whose hemoglobin concentration was three standard deviations above the mean at 12 or 18 weeks’ gestation had a 1.3- to 1.8-fold greater incidence of fetal-growth restriction. Placental weight correlates negatively with maternal hemoglobin concentration (Larsen, 2016). These findings have led some to the illogical conclusion that withholding iron supplementation to cause iron-deficiency anemia will improve pregnancy outcomes (Ziaei, 2007).
The two most common causes of anemia during pregnancy and the puerperium are iron deficiency and acute blood loss. In a study of more than 1300 women, 21 percent had third-trimester anemia, and 16 percent had iron-deficiency anemia (Vandevijvere, 2013). In a typical singleton gestation, the maternal need for iron averages nearly 1000 mg. Multifetal gestational requirements are considerably higher (Ru, 2016). These amounts exceed the iron stores of most women and result in iron-deficiency anemia unless supplementation is given.
Iron deficiency is often manifested by an appreciable drop in hemoglobin concentration. In the third trimester, additional iron is needed to augment maternal hemoglobin and for transport to the fetus. Because the amount of iron diverted to the fetus is similar in a normal and in an iron-deficient mother, the newborn of a severely anemic mother does not suffer from iron-deficiency anemia. Neonatal iron stores are related to maternal iron status and to timing of cord clamping.
Classic morphological evidence of iron-deficiency anemia is erythrocyte hypochromia and microcytosis (Fig. 56-3). This may be less prominent in the pregnant woman. Serum ferritin levels are lower. And, levels of hepcidin—the master regulator of iron availability—are decreased normally in pregnancy. With iron deficiency, hepcidin levels follow those of serum ferritin (Camaschella, 2015; Koenig, 2014).
This peripheral blood smear from a women with iron-deficiency anemia contains many scattered microcytic and hypochromic red cells with characteristic central pallor. These exhibit moderate anisopoikilocytosis, namely, varying sizes and shapes including occasional elliptocytes, which can be oval or pencil-shaped. (Reproduced with permission from Werner CL, Richardson DL, Chang SY, et al (eds): Perioperative Considerations. In Williams Gynecology Study Guide, 3rd ed. New York, McGraw-Hill Education, 2016: Photo contributor: Dr. Weina Chen.)
The initial evaluation of a pregnant woman with moderate anemia includes measurements of hemoglobin, hematocrit, and red cell indices; careful examination of a peripheral blood smear; a sickle-cell preparation if the woman has African origin; and evaluation of serum iron or ferritin levels, or both (Appendix, Serum and Blood Constituents). Serum ferritin levels normally decline during pregnancy, and levels <10 to 15 mg/L confirm iron-deficiency anemia.
When pregnant women with moderate iron-deficiency anemia are given adequate iron therapy, a hematological response is detected by an elevated reticulocyte count. The rate of rise of hemoglobin concentration or hematocrit is typically slower than in nonpregnant women due to the increasing and larger blood volumes during pregnancy.
Routinely in pregnancy, daily oral supplementation with 30 to 60 mg of elemental iron and 400 μg of folic acid is recommended (World Health Organization, 2012). A Cochrane review found that intermittent oral iron supplementation may also be appropriate (Peña-Rosas, 2015). For iron-deficiency anemia, resolution and restitution of iron stores can be accomplished with simple iron salts that provide approximately 200 mg daily of elemental iron. These include ferrous sulfate, fumarate, or gluconate. If a woman cannot or will not take oral iron preparations, then parenteral therapy is given. Although both are administered intravenously, ferrous sucrose is safer than iron-dextran (American College of Obstetricians and Gynecologists, 2017a; Camaschella, 2015; Shi, 2015). Hemoglobin and ferritin levels show equivalent rises in women treated with either oral or parenteral iron therapy (Breymann, 2017; Daru, 2016).
Anemia from Acute Blood Loss
In early pregnancy, anemia caused by acute blood loss is common with abortion, ectopic pregnancy, and hydatidiform mole. Postpartum, anemia commonly stems from obstetrical hemorrhage. Massive hemorrhage demands immediate treatment as described in Chapter 41 (Hypovolemic Shock). If a moderately anemic woman—defined by a hemoglobin value of approximately 7 g/dL—is hemodynamically stable, is able to ambulate without adverse symptoms, and is not septic, then blood transfusions are not indicated. Instead, oral iron therapy is given for at least 3 months (Krafft, 2005).
Anemia Associated with Chronic Disease
Various disorders, such as chronic renal insufficiency, cancer and chemotherapy, human immunodeficiency virus (HIV) infection, and chronic inflammation result in moderate and sometimes severe anemia, usually with slightly hypochromic and microcytic erythrocytes. It is the second most common form of anemia worldwide (Weiss, 2005).
During pregnancy, women with chronic disorders may develop anemia for the first time. In those with preexisting anemia, it may be intensified as plasma volume expands. Causes include chronic renal insufficiency, inflammatory bowel disease, and connective-tissue disorders. Others are granulomatous infections, malignant neoplasms, rheumatoid arthritis, and chronic suppurative conditions.
Chronic renal insufficiency is the most common disorder that we have encountered as a cause of this type of anemia during pregnancy. Some cases are accompanied by erythropoietin deficiency. As discussed in Chapter 53 (Chronic Kidney Disease), during pregnancy in women with mild chronic renal insufficiency, the degree of red cell mass expansion is inversely related to renal impairment. At the same time, plasma volume expansion usually is normal, and thus anemia is intensified (Cunningham, 1990).
For treatment, adequate iron stores must be ensured. Recombinant erythropoietin has been used successfully to treat anemia stemming from chronic disease (Weiss, 2005). In pregnancies complicated by chronic renal insufficiency, recombinant erythropoietin is usually considered when the hematocrit approximates 20 percent (Cyganek, 2011; Ramin, 2006). One worrisome side effect of this agent is hypertension, which is already prevalent in women with renal disease. Red cell aplasia and antierythropoietin antibodies have also been reported (Casadevall, 2002; McCoy, 2008).
These anemias are characterized by blood and bone-marrow abnormalities from impaired DNA synthesis. This leads to large cells with arrested nuclear maturation, whereas the cytoplasm matures more normally. Worldwide, the prevalence of megaloblastic anemia during pregnancy varies considerably. It is rare in the United States.
Megaloblastic anemia developing during pregnancy almost always results from folic acid deficiency. In the past, this condition was referred to as pernicious anemia of pregnancy. It usually is found in women who do not consume fresh green leafy vegetables, legumes, or animal protein. As folate deficiency and anemia worsen, anorexia often becomes intense and further aggravates the dietary deficiency. Drugs and excessive ethanol ingestion either cause or contribute (Hesdorffer, 2015).
In nonpregnant women, the folic acid requirement is 50 to 100 μg/d. During pregnancy, requirements are increased, and 400 μg/d is recommended. The earliest biochemical evidence is low plasma folic acid concentrations (Appendix, Serum and Blood Constituents). Early morphological changes usually include neutrophils that are hypersegmented and newly formed erythrocytes that are macrocytic. With preexisting iron deficiency, macrocytic erythrocytes cannot be detected by measurement of the mean corpuscular volume. Careful examination of a peripheral blood smear, however, usually demonstrates some macrocytes. As the anemia becomes more intense, peripheral nucleated erythrocytes appear, and bone marrow examination discloses megaloblastic erythropoiesis. Anemia may then become severe, and thrombocytopenia, leukopenia, or both may develop. The fetus and placenta extract folate from maternal circulation so effectively that the fetus is not anemic despite severe maternal anemia.
For treatment, folic acid is given along with iron, and a nutritious diet is encouraged. By 4 to 7 days after beginning folic acid treatment, the reticulocyte count is increased, and leukopenia and thrombocytopenia are corrected.
For prevention of megaloblastic anemia, a diet should contain sufficient folic acid. The role of folate deficiency in the genesis of neural-tube defects has been well studied (Chap. 13, Genetic Tests). Since the early 1990s, nutritional experts and the American College of Obstetricians and Gynecologists (2016a) have recommended that all women of childbearing age consume at least 400 μg of folic acid daily. More folic acid is given with multifetal pregnancy, hemolytic anemia, Crohn disease, alcoholism, and inflammatory skin disorders. Women with a family history of congenital heart disease may also benefit from higher doses (Huhta, 2015). Women who previously have had infants with neural-tube defects have a lower recurrence rate if a daily 4-mg folic acid supplement is given.
During pregnancy, vitamin B12 levels are lower than nonpregnant values because of decreased levels of binding proteins, namely, the transcobalamins. During pregnancy, megaloblastic anemia is rare from deficiency of vitamin B12, that is, cyanocobalamin. Instead, a typical example is Addisonian pernicious anemia, which results from absent intrinsic factor that is requisite for dietary vitamin B12 absorption. This autoimmune disorder usually has its onset after age 40 years (Stabler, 2013).
In our limited experience, vitamin B12 deficiency in pregnancy is more likely encountered following gastric resection. Those who have undergone total gastrectomy require 1000 μg of vitamin B12 given intramuscularly each month. Those with a partial gastrectomy usually do not need supplementation, but adequate serum vitamin B12 levels should be ensured (Appendix, Serum and Blood Constituents). Other causes of megaloblastic anemia from vitamin B12 deficiency include Crohn disease, ileal resection, some drugs, and bacterial overgrowth in the small bowel (Hesdorffer, 2015; Stabler, 2013).
Several conditions feature accelerated erythrocyte destruction. Damage may be stimulated by a congenital red-cell abnormality or in other cases by antibodies directed against red-cell membrane proteins. Hemolysis may be the primary disorder, and sickle-cell disease and hereditary spherocytosis are examples. In other cases, hemolysis develops secondary to an underlying condition such as systemic lupus erythematosus or preeclampsia. Microangiopathic hemolytic anemia due to malignancy has been reported in pregnancy (Happe, 2016).
The cause of aberrant antibody production is unknown. Typically, both the direct and indirect antiglobulin (Coombs) tests are positive. Anemias caused by these factors may be due to warm-active autoantibodies (80 to 90 percent), cold-active antibodies, or a combination. These syndromes also may be classified as primary (idiopathic) or secondary due to underlying diseases or other factors. Examples of the latter include lymphomas and leukemias, connective-tissue diseases, infections, chronic inflammatory diseases, and drug-induced antibodies (Provan, 2000). Cold-agglutinin disease may be induced by infectious etiologies such as Mycoplasma pneumoniae or Epstein-Barr viral mononucleosis (Dhingra, 2007). Hemolysis and positive antiglobulin test results may be the consequence of either immunoglobulin M (IgM) or immunoglobulin G (IgG) antierythrocyte antibodies. When thrombocytopenia is comorbid, it is termed Evans syndrome (Wright, 2013).
In pregnancy, hemolysis can be markedly accelerated. Rituximab, along with prednisone, is first-line treatment (Luzzatto, 2015). Coincidental thrombocytopenia usually corrects with therapy. Transfusion of red cells is complicated by antierythrocyte antibodies, but warming the donor cells to body temperature may decrease their destruction by cold agglutinins.
These hemolytic anemias must be differentiated from other causes of autoimmune hemolysis. In most cases, hemolysis is mild, it resolves with drug withdrawal, and recurrence is prevented by avoidance of the drug. One mechanism is hemolysis induced through drug-mediated immunological injury to red cells. The drug may act as a high-affinity hapten when bound to a red-cell protein to which antidrug antibodies attach—for example, IgM antipenicillin or anticephalosporin antibodies. Some other drugs act as low-affinity haptens and adhere to cell membrane proteins. Examples include probenecid, quinidine, rifampin, and thiopental. A more common mechanism for drug-induced hemolysis is related to a congenital erythrocyte enzymatic defect. An example is glucose-6-phosphate dehydrogenase deficiency, which is common in African-American women and discussed later (Aplastic and Hypoplastic Anemia).
Drug-induced hemolysis is usually chronic and mild to moderate, but occasionally acute hemolysis is severe. Garratty and coworkers (1999) described seven women with severe Coombs-positive hemolysis stimulated by cefotetan given as prophylaxis for obstetrical procedures. Alpha-methyldopa can cause similar hemolysis (Grigoriadis, 2013). Moreover, maternal hemolysis has been reported after intravenous immune globulin therapy (Rink, 2013). Withdrawal of the offending drug frequently halts the hemolysis.
Unexplained severe hemolytic anemia can develop during early pregnancy, and it resolves within months postpartum. A clear immune mechanism or red cell defects are not contributory (Starksen, 1983). Because the fetus-neonate also may demonstrate transient hemolysis, an immunological cause is suspected. Maternal corticosteroid treatment is often—but not always—effective (Kumar, 2001). We have cared for a woman who during each pregnancy developed intense severe hemolysis with anemia that was controlled by prednisone. Her fetuses were not affected, and in all instances, hemolysis abated spontaneously after delivery.
In some cases, hemolysis is induced by conditions unique to pregnancy. Mild microangiopathic hemolysis with thrombocytopenia is relatively common with severe preeclampsia and eclampsia (Cunningham, 2015; Kenny, 2015). This HELLP (hemolysis, elevated liver enzyme levels, low platelet count) syndrome is discussed in Chapter 40 (Maternal Thrombocytopenia). Another is acute fatty liver of pregnancy, which is associated with moderate to severe hemolytic anemia (Nelson, 2013). It is discussed in Chapter 55 (Acute Fatty Liver of Pregnancy).
Paroxysmal Nocturnal Hemoglobinuria
Although commonly regarded as a hemolytic anemia, this hemopoietic stem cell disorder is characterized by formation of defective platelets, granulocytes, and erythrocytes. Paroxysmal nocturnal hemoglobinuria is acquired and arises from one abnormal clone of cells, much like a neoplasm (Luzzatto, 2015). One mutated X-linked gene responsible for this condition is termed PIG-A because it codes for phosphatidylinositol glycan protein A. Resultant abnormal anchor proteins of the erythrocyte and granulocyte membrane make these cells unusually susceptible to lysis by complement (Provan, 2000). The most serious complication is thrombosis, which is heightened in the hypercoagulable state of pregnancy.
Chronic hemolysis has an insidious onset, and its severity ranges from mild to lethal. Hemoglobinuria develops at irregular intervals and is not necessarily nocturnal. Hemolysis may be initiated by transfusions, infections, or surgery. Almost 40 percent of patients suffer venous thromboses and may also experience renal failure, hypertension, and Budd-Chiari syndrome. Because of the thrombotic risk, prophylactic anticoagulation is recommended (Parker, 2005). The treatment of choice is eculizumab, an antibody that inhibits complement activation (Kelly, 2015). Median survival after diagnosis is 10 years, and bone marrow transplantation is the definitive treatment.
During pregnancy, paroxysmal nocturnal hemoglobinuria can be serious and unpredictable. Complications have been reported in up to three fourths of affected women, and the maternal mortality rate in the past was 10 to 20 percent (De Gramont, 1987; de Guibert, 2011). Complications more often develop postpartum, and half of affected women develop venous thrombosis (Fieni, 2006; Ray, 2000). Kelly and colleagues (2015) described 75 pregnancies in 61 affected women treated with eculizumab. In half of these, the dose was increased during pregnancy. They described no maternal deaths but 4 percent stillbirths.
The most fulminant acquired hemolytic anemia encountered during pregnancy is caused by the exotoxin of Clostridium perfringens or by group A β-hemolytic streptococcus (Chap. 47, Clinical Manifestations). Endotoxin of gram-negative bacteria, that is, lipopolysaccharide, may be accompanied by hemolysis and mild-to-moderate anemia (Cox, 1991). For example, anemia often accompanies acute pyelonephritis. With normal erythropoietin production, red cell mass is restored following infection resolution as pregnancy progresses (Cavenee, 1994; Dotters-Katz, 2013).
Inherited Erythrocyte Membrane Defects
The normal erythrocyte is a flexible biconcave disc that allows numerous cycles of reversible deformations. Several genes encode expression of erythrocyte structural membrane proteins or intraerythrocytic enzymes. Various mutations of these genes may result in inherited membrane defects or enzyme deficiencies that destabilize the lipid bilayer. The loss of lipids from the erythrocyte membrane causes a surface area deficiency and poorly deformable cells that undergo hemolysis. Anemia severity depends on the degree of rigidity or decreased distensibility. Erythrocyte morphology similarly is dependent on these factors, and these disorders are usually named after the most dominant red-cell shape characteristic of the disorder. Three examples are hereditary spherocytosis, pyropoikilocytosis, and ovalocytosis.
Hemolytic anemias that compose this group of inherited membrane defects are among the most common hemolytic anemias found in gravidas. Mutations are usually an autosomally dominant, variably penetrant spectrin deficiency. Others are autosomally recessive or de novo gene mutations that result from deficiency of ankyrin, protein 4.2, moderate band 3, or combinations of these (Gallagher, 2010; Rencic, 2017; Yawata, 2000). The degrees of anemia and jaundice vary, and diagnosis is confirmed by identification of spherocytes on peripheral smear and increased osmotic fragility.
Spherocytic anemias may be associated with a so-called crisis that is characterized by severe anemia from accelerated hemolysis, and it develops in patients with an enlarged spleen. Infection can also accelerate hemolysis or suppress erythropoiesis to worsen anemia. An example of the latter is infection with parvovirus B19 (Chap. 64, Respiratory Viruses). In severe cases, splenectomy reduces hemolysis, anemia, and jaundice.
In general, women with inherited red-cell membrane defects do well during pregnancy. Folic acid supplementation of 4 mg daily is given orally to sustain erythropoiesis. Women with hereditary spherocytosis cared for at Parkland Hospital had hematocrits ranging from 23 to 41 volumes percent—mean 31 (Maberry, 1992). Reticulocyte counts ranged from 1 to 23 percent. Among 50 pregnancies in 23 women, eight women miscarried. Four of 42 infants were born preterm, but none was growth restricted. Infection in four women intensified hemolysis, and three of these required transfusions. Similar results were reported by Pajor and coworkers (1993).
Because these disorders are inherited, the newborn may be affected. Celkan and Alhaj (2008) report prenatal diagnosis via cordocentesis at 18 weeks’ gestation and testing for osmotic fragility. Newborns with hereditary spherocytosis may manifest hyperbilirubinemia and anemia shortly after birth.
Erythrocyte Enzyme Deficiencies
An intraerythrocytic deficiency of enzymes that permit anaerobic glucose metabolism may cause hereditary nonspherocytic anemia. Most of these mutations are autosomal recessive traits. As discussed earlier (Hemolytic Anemia), most episodes of severe anemia with enzyme deficiencies are induced by drugs or infections.
Pyruvate kinase deficiency is associated with variable anemia and hypertensive complications (Wax, 2007). Due to recurrent transfusions in homozygous carriers, iron overload is frequent, and associated myocardial dysfunction should be monitored (Dolan, 2002). The fetus that is homozygous for this mutation may develop hydrops fetalis from anemia and heart failure (Chap. 15, Hydrops Fetalis).
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is complex because there are more than 400 known enzyme variants. The most common are caused by a base substitution that leads to an amino acid replacement and a broad range of phenotypic severity (Luzzatto, 2015; Puig, 2013). In the homozygous or A variant, both X chromosomes are affected, and erythrocytes are markedly deficient in G6PD activity. Approximately 2 percent of African-American women are affected, and the heterozygous variant is found in 10 to 15 percent (Mockenhaupt, 2003). In both instances, random X-chromosome inactivation—lyonization—results in variable enzyme activity.
During pregnancy, infections or drugs can induce hemolysis in G6PD deficiency heterozygotes or homozygotes, and severity is related to enzyme activity. Anemia is usually episodic, although some variants induce chronic nonspherocytic hemolysis. Because young erythrocytes contain more enzyme activity, anemia ultimately stabilizes and is corrected soon after the inciting cause is eliminated. Newborn screening for G6PD deficiency is not recommended by the American College of Obstetricians and Gynecologists (2016b).
Aplastic and Hypoplastic Anemia
Aplastic anemia is a grave complication that is characterized by pancytopenia and markedly hypocellular bone marrow (Young, 2015). There are multiple etiologies, and at least one is linked to autoimmune diseases (Stalder, 2009). The inciting cause can be identified in approximately a third of cases. These include drugs and other chemicals, infection, irradiation, leukemia, immunological disorders, and inherited conditions such as Fanconi anemia and Diamond-Blackfan syndrome (Green, 2009; Lipton, 2009). The functional defect appears to be a marked decrease in committed marrow stem cells.
Hematopoietic stem-cell transplantation is optimal therapy in a young patient (Killick, 2016). Immunosuppressive therapy is given, and in some nonresponders, eltrombopag has been successful (Olnes, 2012; Townsley, 2017). Definitive treatment is bone marrow transplantation, and approximately three fourths of patients have a good response and long-term survival (Rosenfeld, 2003). Umbilical cord blood-derived stem cells can also serve as a potential transplant source (Moise, 2005; Pinto, 2008). Previous blood transfusions and even pregnancy enhance the risk of graft rejection (Young, 2015).
Hypoplastic or aplastic anemia complicating pregnancy is rare. A study of 60 pregnancies complicated by aplastic anemia found that half were diagnosed during pregnancy (Bo, 2016). There are a few well-documented cases of pregnancy-induced hypoplastic anemia, and the anemia and other cytopenias improve or remit following delivery or pregnancy termination (Bourantas, 1997; Choudhry, 2002). In some cases, anemia recurred in a subsequent pregnancy.
Diamond-Blackfan anemia is a rare form of pure red-cell hypoplasia. Approximately 40 percent of cases are familial and have autosomal dominant inheritance (Orfali, 2004). The response to glucocorticoid therapy is usually good. Continuous treatment is necessary, and most become at least partially transfusion dependent (Vlachos, 2008). In 64 pregnancies complicated by this syndrome, Faivre and associates (2006) reported that two thirds had problems related to placental vascular etiologies that included miscarriage, preeclampsia, preterm birth, fetal-growth restriction, or stillbirth.
Gaucher disease is an autosomally recessive lysosomal enzyme deficiency characterized by deficient activity of acid β-glucosidase. Affected women have anemia and thrombocytopenia that is usually worsened by pregnancy (Granovsky-Grisaru, 1995). Elstein and colleagues (1997) described six pregnant women whose disease improved when they were given alglucerase enzyme replacement. Imiglucerase therapy, which is human recombinant enzyme replacement therapy, has been available since 1994. European guidelines recommend treatment in pregnancy, whereas the Food and Drug Administration states it may be given with “clear indications” (Granovsky-Grisaru, 2011).
The major risks with hypoplastic anemia are hemorrhage and infection. Rates of preterm labor, preeclampsia, fetal‑growth restriction, and stillbirth are increased (Bo, 2016). Management depends on gestational age, and supportive care includes continuous infection surveillance and prompt antimicrobial therapy. Granulocyte transfusions are given only during infections. Red cells are transfused to improve symptomatic anemia and routinely to maintain the hematocrit at or above 20 volumes percent. Platelet transfusions may be needed to control hemorrhage. Maternal mortality rates reported since 1960 have averaged nearly 50 percent, however, better outcomes have been reported more recently (Choudhry, 2002; Kwon, 2006).
Pregnancy after Bone Marrow Transplantation
Several reports describe successful pregnancies in women who have undergone bone marrow transplantation (Borgna-Pignatti, 1996; Eliyahu, 1994). In their review, Sanders and coworkers (1996) reported 72 pregnancies in 41 women who had undergone transplantation. In the 52 pregnancies resulting in a liveborn neonate, almost half were complicated by preterm delivery or hypertension. Our experiences with a few of these women indicate that they have normal pregnancy-augmented erythropoiesis and total blood volume expansion.