Baby on board: what you need to know about pregnancy in the hemoglobinopathies Rakhi P. Naik 1 and Sophie Lanzkron 1 1 Department of Medicine, Division of Hematology, Johns Hopkins University, Baltimore, MD Pregnancy poses a unique challenge to patients with sickle cell disease and -thalassemia, who often have exacerbations of hemolysis or anemia during the gestational period, experience higher rates of obstetric and fetal complications, and may have distinct underlying comorbidities related to vasculopathy and iron overload that can endanger maternal health. Optimal management of pregnant women with hemoglobinopathies requires both an understanding of the physiologic demands of pregnancy and the pathophysiology of disease-specific complications of inherited blood disorders. A multidisciplinary team of expert hematologists and high-risk obstetricians is therefore essential to ensuring appropriate antenatal maternal screening, adequate fetal surveillance, and early recognition of complications. Fortunately, with integrated and targeted care, most women with sickle cell disease and -thalassemia can achieve successful pregnancy outcomes. Introduction Sickle cell disease (SCD) and -thalassemia are autosomal- recessive disorders of the -globin gene that result in severe anemia. In SCD, a point mutation of the -globin gene results in the production of an abnormal hemoglobin (HbS) that polymerizes in its deoxygenated state and forms sickle-shaped RBCs. 1 Acute complications of the disease such as pain crisis and acute chest syndrome (ACS) are due in part to vasoocclusion from direct entrapment of the deformed RBCs in the microcirculation, whereas chronic sequelae such as pulmonary hypertension and leg ulceration result from long-term toxic effects from intravascular hemolysis and vascular dysfunction. 2 In -thalassemia, decreased or absent synthe- sis of the -globin gene results in ineffective erythropoiesis and significant anemia secondary to both underproduction and hemoly- sis from unstable -globin inclusions. 3 Although the clinical manifestations of -thalassemia depend on modifying genetic factors, morbidity associated with the disease is common. Extensive extramedullary hematopoiesis in -thalassemia patients can lead to early complications such as skeletal deformities and spleno- megaly, and iron overload due to increased gut iron absorption and transfusion therapy results in late organ dysfunctions such as endocrine abnormalities and cardiac failure. 3 Approximately 90 000 people are affected by SCD in the United States alone, 4 and although the prevalence of -thalassemia major (TM) in the United States is estimated at only 1000, 5 -thalassemia subtypes, including both -TM and -thalassemia intermedia (TI), affect a considerable proportion of births worldwide, especially in areas with high carrier frequency such as India and southeast Asia. 6 Improvements in the overall management of hemoglobinopathies have allowed affected persons to enjoy an improved quality of life and increased life expectancy. However, pregnancy can lead to maternal and fetal complications in SCD and -thalassemia pa- tients, even in those who are otherwise asymptomatic. Because research regarding the optimal management of pregnant patients with inherited hemoglobin disorders is sparse, specialty care with trained hematologists and maternal-fetal specialists familiar with hemoglobinopathies is essential for the treatment of these disorders and their complications during gestation. Clinically severe -thalas- semia syndromes such as hemoglobin H disease variants are rare 6 and the management of pregnant women with -thalassemia and a prenatal diagnosis of hydrops fetalis are beyond the scope of this review. Maternal and fetal complications SCD Pregnancy results in a myriad of physiologic changes that can interact adversely with sickle hemoglobin to promote abnormal RBC sickling. Oxygen demand during pregnancy increases to support the metabolic requirements of the developing placenta and fetus. 7 Although normal compensatory mechanisms such as an increased blood volume often result in adequate maternal and fetal oxygen delivery in a healthy woman, the need for an increased plasma volume relative to erythrocyte production can significantly worsen anemia in patients who already have severely low hemoglo- bin levels and shortened erythrocyte survival. Furthermore, the maternal oxygen reserve may be compromised during pregnancy secondary to the increased oxygen consumption and decreased functional residual capacity during gestation, 7 which may predis- pose SCD patients to hypoxemia and subsequent exacerbation of sickling. Therefore, maternal and fetal morbidity in SCD stems from an increase in both pregnancy-related complications relating to the degree of anemia and impaired oxygen delivery and complica- tions associated with SCD itself. Although there is a general consensus that the overall risk of complications during pregnancy for patients with SCD is increased, frequency estimates for specific obstetric outcomes have varied widely between studies. The largest cohort study from the Coopera- tive Study of Sickle Cell Disease found generally favorable outcomes in 445 pregnancies, 286 of which progressed through to delivery. 8 In that study, of the pregnancies that were not electively terminated, 89.3% progressed to live births, with a mean gestational age of 37.7 weeks. In addition, mortality was low, with only 2 pregnancies resulting in maternal death, and rates for miscarriage (6.5%) and non–SCD-related obstetric complications were not found to be increased in women with SCD compared with the HEMATOLOGIC DISEASES IN PREGNANCY 208 American Society of Hematology