Anemia and Thrombocytopenia in Pregnancy

Anemia With normal pregnancy, blood volume increases, which results in a concomitant hemodilution. Although red blood cell mass increases during pregnancy, plasma volume increases more, resulting in a relative anemia. This results in a physiologically lowered hemoglobin (Hb) level, hematocrit (Hct) value, and red blood cell (RBC) count, but it has no effect on the mean corpuscular volume (MCV). Many centers define anemia in a patient who is pregnant as an Hb value less than 10.5 g/dL, as opposed to the reference range of 14 g/dL in a patient who is not pregnant. Treatment with 1 mg folic acid and daily iron is helpful when deficiencies are noted. Iron deficiency anemia Iron deficiency anemia accounts for 75-95% of the cases of anemia in pregnant women. A woman who is pregnant often has insufficient iron stores to meet the demands of pregnancy. Encourage pregnant women to supplement their diet with 60 mg/d of elemental iron. An MCV less than 80 mg/dL and hypochromia of the RBCs should prompt further studies, including total iron-binding capacity, ferritin levels, and Hb electrophoresis if iron deficiency is excluded. Clinical symptoms of iron deficiency anemia include fatigue, headache, restless legs syndrome, and pica (in extreme situations). Treatment is additional supplementation with oral iron sulfate (320 mg, 1-3 times daily). Iron is preferable once daily because more frequent iron supplementation can cause constipation. The clinical consequences of iron deficiency anemia include preterm delivery, perinatal mortality, and postpartum depression. Fetal and neonatal consequences include low birth weight and poor mental and psychomotor performance.1 Folate and vitamin B-12 deficiency Folate deficiency is much less common than iron deficiency; however, taking 0.4 mg/d to reduce the risk of neural tube defects is recommended to all women contemplating pregnancy. Patients with a history of neural tube defect should take 4 mg/d. An increased MCV can be suggestive of folate deficiency; in this case, determine serum levels of vitamin B-12 and folate. If the levels are low, the patient may require oral folate at a dose of 1 mg 3 times daily. Patients with vitamin B-12 deficiency need further workup to determine the level of intrinsic factor to exclude pernicious anemia. The Schilling test is not recommended during pregnancy because of the radionuclide used in testing. Treatment of vitamin B-12 deficiency includes 0.1 mg/d for 1 week, followed by 6 weeks of continued therapy to reach a total administration of 2 mg. Infectious causes of anemia Although rare, anemia can be caused by infections such as parvovirus B-19, CMV, HIV, hepatitis viruses, EBV, malaria, babesiosis, bartonellosis, and clostridium toxin. If the patient's history suggests exposure to any of these infectious agents, appropriate laboratory studies should be performed. Diamond-Blackfan anemia This is a rare (7 per 1 million) autosomal dominant disorder of pure red cell aplasia requiring life-long transfusion. Women who are contemplating or who are pregnant require the consultation and care of a hematologist in conjunction with a Maternal Fetal Medicine specialist. Concerns during pregnancy include maintaining adequate hemoglobin while decreasing the risk of fetal exposure to the iron chelating agent (Deferoxamine) used during transfusions. 1 Sickle Cell Hemoglobinopathies Sickle cell hemoglobinopathies include those abnormalities resulting from an alteration in structure, function, or production of Hb. Hemoglobin S (HbS) results from substitution of thymine for adenine in the beta-globin gene, which leads to the substitution of the neutral amino acid valine for the negatively charged glutamic acid at the sixth position from the N terminus in the beta chain. Hemoglobin C (HbC) results from a lysine substitution for glutamic acid. Major sickle disorders with severe clinical symptoms include sickle cell anemia (HbSS), sickle cell hemoglobin C (HbSC) disease, and sickle cell beta-thalassemia (HbS beta-Thal). Minor disorders include hemoglobin C disease (HbAC), hemoglobin SE (HbSE), hemoglobin SD (HbSD), and hemoglobin S-Memphis (HbS-Memphis). Heterozygosity for hemoglobin A and hemoglobin S (HbAS) is the most common disorder. HbS is also known as sickle cell trait and occurs in 1 in 12 African

Americans. HbSS is the most common major sickle cell disorder, occurring in 1 in 625 African Americans. HbS is also found in other populations, such as Greeks, Italians (particularly Sicilians), Turks, Arabs, Southern Iranians, and Asian Indians. Diagnosis of hemoglobinopathies is made by hemoglobin electrophoresis. Anemia occurs as a result of the sickle hemoglobinopathies. Deoxygenation of the abnormal RBCs results in sickling. These permanently damaged RBCs are then removed by the reticuloendothelial system, with the average RBC lifespan reduced to 17 days. The result is a chronic compensated anemia, with Hb typically measured between 6.5 and 9.5 g/dL. The sickle shape also results in altered motion through the microvasculature. This altered motion can predispose the patient to vascular stasis, hypoxia, acidosis, and increased 2,3 diphosphoglycerate, which perpetuates the cycle by resulting in further deoxygenation and, thus, more sickling. The microvascular injury can result in ischemic necrosis and end-organ infarction. Organs affected by chronic sickling include the spleen, lungs, kidneys, heart, and brain. Patients with sickle cell anemia are functionally asplenic. Therefore, immunization for encapsulated organisms (pneumococcus and meningococcus) is recommended. Likewise, aggressive treatment should be instituted when encapsulated bacterial infections are diagnosed in sickle cell disease. Maternal and fetal morbidity In general, treating a pregnant woman who has sickle cell disease requires close observation. Obtain blood cell counts frequently because anemia can worsen quickly. Folic acid supplementation is recommended because of the quick turnover of erythrocytes. Monitor the pregnancy with serial ultrasounds for fetal growth, and implement weekly fetal surveillance at 32 weeks' gestation. Offer the patient pneumococcal and meningococcal vaccines before pregnancy, if possible. Prophylactic RBC transfusion was once standard in patients who were pregnant and had sickle cell disease; however, it is no longer routinely advised. In 1988, a National Institutes of Health (NIH) sponsored, multicenter, randomized, controlled trial of 72 patients with HbSS disease showed no significant difference in overall maternal or perinatal outcome of patients who received transfusions and those who did not, except for a lower incidence of painful crises in patients who received transfusions. 2 The risks incurred with multiple blood transfusions include infection and alloimmunization, which have their own implications for pregnancy. Similar findings have been reported in a more heterogenous group of patients from the United Kingdom (including patients with HbSS, HbSC, and HbS beta-Thal), although some evidence indicates that the subset of women with sickle hemoglobinopathies carrying twins or higher-order multiples may benefit from prophylactic transfusion. A woman who is pregnant is at risk of developing sickle cell crisis (SCC). These crises typically are vasoocclusive and may be precipitated by infection. They may be associated with thrombophlebitis or preeclampsia. Commonly, a pattern of sudden recurrent attacks of pain involving the abdomen, chest, vertebrae, or extremities occurs. These crises are somewhat more common in HbSS disease than HbSC and HbS beta-Thal disease. Laboratory tests that may be helpful to distinguish between SCC and other possible etiologies of pain include WBC count with differential and lactic dehydrogenase (LDH) determinations. An elevated WBC count may be observed in cases of SCC, but a left shift should not be observed. Patients with SCC have elevated LDH levels. Other laboratory tests that should be ordered upon patient admission include CBC count, type and cross match, and arterial blood gas determinations as indicated. Therapeutic measures for SCC mainly are supportive, with institution of intravenous fluids to decrease blood viscosity and pain control as standard pillars of care. If a sudden drop in Hct occurs, therapeutic transfusion may be advisable. Identification and treatment of any underlying infection is of paramount importance. If the fetus is viable, continuous fetal heart rate monitoring is necessary if maternal oxygenation is compromised. The mother and fetus may benefit from supplemental oxygen. Remember that fetal heart rate tracings may be nonreactive and the blood pressure and pulse (BP&P) may be abnormal during crisis; BP&P typically revert to normal when the crisis resolves. Umbilical artery Doppler study findings have also been noted as frequently being normal during crisis, even in the setting of abnormal uterine artery Doppler study results. Overall, great improvement has occurred in maternal and fetal outcome in patients with sickle cell disease. A widely quoted study from West Africa in the early 1970s reports an 11.5% mortality rate in mothers who are homozygous. Other investigators noted a decrease in maternal death rates at Los Angeles County Hospital from 4.1% in the era before 1972 to 1.7% from 1972-1982, with all deaths occurring in patients with HbSS or HbS beta-Thal disease. A decade later, the NIH-sponsored Cooperative Study of Sickle Cell Disease reported 2 deaths in 445 (0.6%) pregnancies.3 Both of these deaths occurred in patients with HbSS. Few reported maternal deaths have been associated with HbSC disease in the last 2 decades. The Cooperative Study also found earlier gestational ages at delivery, smaller birth weights, and an increased rate of stillbirths (0.9%) in the HbSS

group, as well as a greater rate of painful crises (50%). 3 No difference in the rates of preeclampsia existed among the different genotypes, and surprisingly, little pyelonephritis occurred (<1%). Most likely, an increase in first trimester fetal wastage occurs; however, correctly ascertaining this rate in the modern era is difficult because many women with this disease electively terminate their pregnancies. The most recent data on SCD in pregnancy comes from a study by Chakravarty et al in 2008, which examined Nationwide Inpatient Sample data. In their study, they found increased risk for antenatal hospitalization, hypertensive disorders, IUGR, and cesarean delivery for women with SCD. Odds ratio (OR) for IUGR in their study was 2.91. Also of significance was the OR of 5.56 for antenatal hospitalizations for women with SCD.4 Despite the improvement in survival of both mother and fetus, remember that patients with the sickle hemoglobinopathies remain at risk for renal insufficiency, cerebrovascular accident, cardiac dysfunction, leg ulcers, and sepsis, particularly from encapsulated organisms. Thalassemia Thalassemia is a disease with many forms, all of which are characterized by impaired production of one of the normal globin peptide chains found in Hb. Healthy adults should have more than 95% hemoglobin A (HbA), consisting of 2 alpha and 2 beta peptide chains. Other polypeptide chains are gamma, delta, epsilon, and zeta. Hemoglobin F (fetal hemoglobin, HbF) consists of 2 alpha chains and 2 gamma chains. HbA2 consists of 2 alpha chains and 2 delta chains. Depending on the hemoglobinopathy, some of these other types of hemoglobin may be found on electrophoresis. Presence of these less common adult forms should signal the need for further investigation of a hemoglobinopathy. The 2 major thalassemias, alpha-thalassemia and beta-thalassemia, result from decreased production of one or more of these peptide chains. The clinical consequences can be ineffective erythropoiesis, hemolysis, and anemia of varying degrees. Consultation with a maternal fetal medicine specialist is often wise. The disease is found throughout the world, but its highest prevalence is in areas endemic for malaria, where it may confer a heterozygote advantage. These regions include the Mediterranean, central Africa, and parts of Asia. Inheritance is autosomal recessive. A lethal homozygous state results when an individual inherits genes for both alpha and beta chains. Various defects that may be responsible for the different thalassemia syndromes have been implicated on a molecular level. In most populations, the gene loci for the alphaglobin chains are located on the short arm of chromosome 16. The beta chain gene is located on the short arm of chromosome 11. Geographical variation exists with the various syndromes. HbBart and hemoglobin B (HbB) principally affect people of Asian descent. Alpha-thalassemia Alpha-thalassemias comprise one of the major thalassemias. In alpha-thalassemia, a loss of 2 or more of the 4 alpha-globin genes occurs. Deletion of 1 alpha-globin gene is of no clinical consequence and laboratory values are in the normal range. Four clinical syndromes have been described. The homozygous condition results when all 4 genes for the alpha-globin chain are deleted and the fetus is unable to synthesize HbF or any adult Hbs. This condition results in HbBart as the predominant Hb. Because of its high oxygen affinity, little oxygen is released to the tissues. The fetus develops nonimmune hydrops and typically dies in utero or shortly after birth. Preeclampsia can develop in the patient carrying a fetus with alpha-thalassemia major. Hemoglobin H (HbH) disease is a compound heterozygous state that results in the deletion of 3 of 4 alphaglobin genes. The abnormal red cells at birth consist of both HbH and HbBart. The neonate appears healthy at birth but then develops hemolytic anemia. Ultimately, the HbBart is replaced with HbH. The result is anemia, which varies in severity and can worsen significantly during pregnancy. Alpha-thalassemia minor is the heterozygous state, which results from a deletion of 2 genes and causes a mild-to-moderate hypochromic microcytic anemia. Patients with this condition typically do well during pregnancy. Alpha-thalassemia minor or alpha-thalassemia trait exists when 2 alpha chain genes are missing. It is common in people of African, Southeast Asian, West Indian, and Mediterranean decent. The inheritance can be either cis (--/alpha, alpha), that is one chromosome without either copy and one with 2 copies, or trans (alpha,-/alpha,-), each chromosome has only one copy of the alpha-globin gene. Patients with the cis pattern are at greater risk of having a baby with HbBart or HbH disease. An article published by Leung et al describes the use of ultrasonographic markers during pregnancy to predict fetuses at risk for alpha-thalassemia major.5 This may prove to be a useful and attractive option for some patients. Beta-thalassemia

The beta-thalassemias are the consequence of one of many point mutations that cause absence of or reduction in beta-chain production. HgA is usually absent in these individuals. Elevated levels of HbF can often be found. Beta-thalassemia major, or Cooley anemia, is characterized by precipitation of the excessive alpha chains that results in ineffective erythropoiesis and hemolysis. The fetus is protected from this because of high levels of HbF; however, after birth, as HbF levels fall, the infant becomes anemic. Although transfusion can prolong life, especially when combined with iron chelation therapy, females with this disorder historically have been infertile. However, the number of successful pregnancies in these patients has been increasing. These patients require frequent transfusions and deferoxamine iron chelation therapy throughout pregnancy. Beta-thalassemia minor occurs in individuals who are heterozygous for the gene mutation and therefore have variable production of the beta globin chain. As a consequence, beta-thalassemia minor has variable clinical effects, depending on the rate of beta-chain production. It may be unmasked during pregnancy or uncovered after a patient has delivered a homozygous infant. Hb electrophoresis characteristically shows a minor fraction of adult hemoglobin (HbA2), which consists of 2 alpha and 2 delta chains, to be increased to greater than 3.5%. In the presence of iron deficiency anemia, the amount of HgA2 may be falsely normal. These patients do not have impaired fertility or pregnancy outcome; however, they may become disproportionately anemic and require iron or folate supplementation during pregnancy. The obstetric emphasis with these patients who are heterozygous is on prenatal diagnosis. Like the alpha-thalassemias, the beta-thalassemias are common in individuals of Mediterranean, Asian, Middle Eastern and West Indian descent. Hispanics have a higher prevalence for thalassemia than Caucasians; therefore, these disorders should be considered in the differential diagnosis for anemia in Hispanic patients as well. Screening and Genetic Testing for the Hemoglobinopathies Advances in genetic research that allow precise identification of mutations of the Hb genes make the process of identifying couples at risk for having offspring with the hemoglobinopathies increasingly important for obstetrician-gynecologists. Although universal screening is not recommended, submit CBC counts with RBC indices for all pregnant women at the initiation of prenatal care. Pay particular attention to patients of Southeast Asian, Mediterranean, or African descent. Order Hb electrophoresis in patients with these ethnic backgrounds to evaluate for sickle hemoglobinopathies. Also, refer patients who are from Southeast Asia or the Mediterranean and have anemia and reduced MCV (<80 m 3) and normal iron study findings for Hb electrophoresis. Inquire about previous pregnancies and family history of adverse pregnancy outcomes. If Hb is normal in patients who are of Southeast Asian descent, specifically evaluate for alpha-thalassemia. Offer to test the partner of any carrier of sickle hemoglobinopathies and any patient with elevated HbA2 (>3.5%) to assess the risk to the fetus. If both partners are identified as carriers, offer DNA-based tests for the fetus. Tests for prenatal diagnosis of sickle cell anemia and thalassemia now include polymerase chain reaction (PCR) of fetal DNA extracted from amniotic cells, of trophoblasts from chorionic villus sampling, and of erythroblasts obtained from cordocentesis. In many hemoglobinopathies, including sickle cell disease and most beta-thalassemias, point mutations exist for which specifically designed oligonucleotide probes can be used, especially in combination with knowledge of the patient's ethnicity. For some thalassemias, performing indirect DNA testing by linkage analysis is still necessary. Efforts to reduce the risks to the fetus incurred with invasive tests such as amniocentesis, chorionic villus sampling, and cordocentesis have been made by acquisition of fetal cells from the maternal circulation using magnetic cell sorting; however, this procedure is not standard. This technique can only work in hemoglobinopathies in which the mutation has been identified because only a small amount of fetal cells can be purified. Many couples elect to continue an affected pregnancy. Preimplantation genetics can now be offered to assure the placement of unaffected embryos in utero. One more genetic test should be considered in patients with anemia who are of African, Mediterranean, Indian, and Southeast Asian descent. This is a test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. This deficiency appears to be common in these populations because G6PD deficiency seems to confer relative protection from Plasmodium falciparum malaria. The G6PD gene is on the X chromosome and therefore follows a sex-linked pattern. Because of lyonization in red blood cells, a variable proportion of RBCs are affected in women who are heterozygous for the deficiency. Therefore, heterozygous women can have mild, moderate, or severe anemia. Thrombocytopenia Thrombocytopenia in pregnancy is common and is diagnosed in approximately 7% of pregnancies. It is typically defined as a platelet count of less than 150,000/L. The most common cause of thrombocytopenia during pregnancy is gestational thrombocytopenia, which is a mild thrombocytopenia with platelet levels remaining greater than 70,000/L.

Patients who are affected usually are asymptomatic and have no history of thrombocytopenia prior to pregnancy. Their platelet levels should return to normal within several weeks following delivery. An extremely low risk of fetal or neonatal thrombocytopenia is associated with gestational thrombocytopenia. Gestational thrombocytopenia may result from increased platelet consumption and can be associated with antiplatelet antibodies. Gestational thrombocytopenia can be hard to distinguish fromimmune thrombocytopenia purpura (ITP) presenting during pregnancy. Immune thrombocytopenia purpura Acute ITP is a disorder occurring in childhood with little implication for women who are pregnant because it resolves spontaneously. Chronic ITP may occur in the second or third decade of life, affecting females 3 times as frequently as males. This condition is characterized by immunologically mediated platelet destruction. Antiplatelet antibodies (immunoglobulin G) attack platelet membrane glycoproteins and destroy platelets at a rate that cannot be compensated by the bone marrow. ITP is usually associated with persistent thrombocytopenia (<100,000/L), normal or increased megakaryocytes on bone marrow aspirate, exclusion of other disorders associated with thrombocytopenia, and the absence of splenomegaly. Patients may report a history of easy bruising and petechiae or epistaxis and gingival bleeding preceding the pregnancy. Although worsening of the disease is not typical during pregnancy, when it occurs, the mother is at risk for bleeding complications at the time of delivery. Therapies aimed at improving the maternal platelet count in anticipation of delivery include intravenous immunoglobulin (IVIg) and steroids. The patient may require platelet transfusion during delivery if the platelet count drops below 20,000/L. Splenectomy is reserved for severe cases only. Some controversy exists regarding the threat of intracranial hemorrhage (ICH) in neonates born to mothers with ITP. Although as many as 12-15% of infants born to mothers with ITP may develop platelet counts less than 50,000/L, the risk of ICH is estimated at less than 1% in 2 recent prospective studies. Neonatal alloimmune thrombocytopenia In contrast to ITP, neonatal alloimmune thrombocytopenia may pose a serious risk to the newborn. It may occur in 1 in 1000 live births and often is unanticipated when it occurs in first pregnancies. The presentation may be in the setting of an unremarkable pregnancy and delivery. Clinical manifestations in the neonate include generalized petechiae, ecchymoses, hemorrhage into viscera, increased bleeding at the time of circumcision or venipuncture, or, most gravely, ICH. ICH may occur in utero in as many as 25% of cases. Like Rhesus (Rh) disease, neonatal alloimmune thrombocytopenia results from maternal alloimmunization against fetal platelet antigens. The most severely affected antigen is human platelet antigen-1a, which has been described in approximately 50% of cases in white persons. A high risk of recurrence of neonatal alloimmune thrombocytopenia exists, and it tends to worsen with subsequent gestations in a manner similar to Rh disease. For patients who have a history of the disease and are experiencing their first pregnancy, referral to a maternal-fetal medicine specialist skilled in cordocentesis may be warranted because the fetus may need to have platelet counts or a transfusion while in utero. IVIg has been shown to improve fetal thrombocytopenia. Cesarean delivery is the preferred route of delivery for infants with platelet counts less than 50,000/L to reduce the risk of ICH secondary to trauma incurred during labor. Coagulation Disorders von Willebrand disease This is the most common inherited bleeding abnormality, with a prevalence rate of 0.8-1.3%. This disorder is secondary to a decrease or defect in the von Willebrand portion of the factor VIII complex, which plays a significant role in platelet aggregation. Type I, which is inherited in an autosomal dominant fashion, is the most common subtype (>70% of cases). Patients may present with menorrhagia, easy bruising, gingival bleeding, and epistaxis or with abnormal bleeding following surgery or trauma. Laboratory findings in patients with type I disease typically show a prolonged bleeding time from decreased platelet aggregation, decreased von Willebrand factor (vWF), decreased factor VIII:C, and sometimes, a prolonged activated partial thromboplastin time. Mild thrombocytopenia may occur. In patients with type II disease, normal amounts of abnormally functioning vWF may exist. Type III disease is very rare and is characterized by very low vWF. Type III disease tends to have a more severe course. During pregnancy, a patient with type I disease may have improvement in the bleeding time secondary to an increase in factor VIII:C, although these beneficial effects are not seen until after the first trimester. Thus, patients are at the highest risk of bleeding problems early in pregnancy and in the puerperium. In one series from the United Kingdom, 33% of patients had first trimester bleeding and the miscarriage rate was 21%, not unlike rates observed in the healthy population. However, patients had increased rates of postabortal transfusion, persistent bleeding, and an increased need for repeat dilatation and curettage. Measure factor VIII:C and bleeding time in patients at their first and third trimester. Historically, cryoprecipitate has been

advised when factor levels fall below 80% of the reference level (approximately 50 IU/dL) or when anything but an uncomplicated vaginal delivery is anticipated. Because of the concern of infection risk with products from pooled donors, deamino-8-D-arginine vasopressin (DDAVP) is now used in many patients, particularly those with type I disease. Another product that can be used at the time of anticipated bleeding is Humate-P, a concentrate of many high molecular proteins needed to replace vWF. A woman with mild disease may not need these measures in case of an uncomplicated vaginal delivery. Avoid epidural and spinal anesthesia in all patients, except those with mild disease. In the case of cesarean delivery, transfusion generally is recommended. Patients are at increased risk of postpartum hemorrhage; monitor levels of factor VIII:C and bleeding. Because type I disease is autosomal dominant (although with variable penetrance), avoid fetal scalp electrodes during labor and evaluate the neonate before circumcision. Hemophilia A This is an X-linked recessive disorder characterized by a decrease in factor VIII:C. Women who are homozygous are extremely rare and require fresh frozen plasma or cryoprecipitate at the time of delivery to prevent postpartum hemorrhage. The main obstetric concern is the risk to the offspring. The risk to a male fetus is 50%. Chorionic villus sampling can help determine if the fetus is at risk by determining fetal sex and providing tissue for DNA analysis. Hemophilia B This X-linked recessive disorder is also known as Christmas disease. Patients have a deficiency in factor IX. Carriers typically have no clinical manifestations. Prenatal diagnosis is limited to determination of fetal sex. Drug and Medication Exposure Various medications and drug exposures can lead to anemia. Most pregnant women and their obstetricians are careful about what medicines are administered or ingested during pregnancy. On occasion, drugs that can cause anemia are required. A good example is the pregnant woman who is diagnosed with breast cancer in early pregnancy and requires chemotherapy, which is an increasingly more common clinical scenario. Below is a list of drugs and the possible underlying causes 6 : Open table in new window
Drug/Medication Penicillin, cephalosporin, procainamide, quinidine, quinine, sulfonamide Fava beans, dapsone, naphthalene Cancer chemotherapeutic medications Chloramphenicol, gold salts, sulfonamides, anti-inflammatory drugs Ethanol, chloramphenicol Methotrexate, azathioprine, pyrimethamine, trimethoprim, sulfa drugs, zidovudine, hydroxyurea Past chemotherapy drugs Drug/Medication Penicillin, cephalosporin, procainamide, quinidine, quinine, sulfonamide Fava beans, dapsone, naphthalene Cancer chemotherapeutic medications Chloramphenicol, gold salts, sulfonamides, anti-inflammatory drugs Ethanol, chloramphenicol Methotrexate, azathioprine, pyrimethamine, trimethoprim, sulfa drugs, zidovudine, hydroxyurea Past chemotherapy drugs Potential Etiology for Anemia Drug-induced hemolytic anemia Oxidant-induced hemolysis (G-6-PD deficient) Bone marrow suppression, oxidant damage, fluid retention/dilutional anemia Bone marrow hypoplasia Acute reversible bone marrow toxicity Bone marrow aplasia/hypoplasia, megaloblastic anemia Bone marrow suppression, AML, myelodysplasia Potential Etiology for Anemia Drug-induced hemolytic anemia Oxidant-induced hemolysis (G-6-PD deficient) Bone marrow suppression, oxidant damage, fluid retention/dilutional anemia Bone marrow hypoplasia Acute reversible bone marrow toxicity Bone marrow aplasia/hypoplasia, megaloblastic anemia Bone marrow suppression, AML, myelodysplasia

Unexplained Maternal Anemia When unexplained maternal anemia presents, this can be quite vexing to obstetricians and other medical specialists. In such cases, considering all potential causes for anemia including, but not limited to, medication, infectious, and immunologic causes, is prudent. Supportive measures for the pregnant woman should be instituted while pursuing the etiology for anemia. Medications that can cause anemia are listed above. Other considerations in this category should include alcohol consumption. There is a population of pregnant women who have alcoholism and consume alcohol without revealing this to their obstetricians. Women should be carefully queried regarding their alcohol use. An example of unexplained anemia was reported in 2008 by Katsuragi et al; they reported a Japanese woman with severe hemolytic anemia with negative results on direct and indirect Coombs tests. 7 IgG levels on the patient's RBCs were increased during her pregnancy and resolved postpartum. All other antibody test results were likewise negative. Screening test results for all hemoglobinopathies were also negative. The patient was successfully treated with prednisolone and RBC transfusions and delivered at 35 weeks' gestation. Infectious causes, though rare, include viral etiologies such as HIV, CMV, EBV, Parvovirus B-19, and the hepatitis viruses. Other infectious causes include brucellosis and tuberculosis.

Rh Incompatibility
Updated: Nov 4, 2009

Author: Leon Salem, MD, MS, Associate Attending Physician, Kaiser Permanente, Southern California Coauthor(s): Karen R Singer, PA-C, Department of Pediatrics, Fountain Valley Medical Center, South Counties Pediatric Critical Care Medical Group, Fountain Valley and Long Beach, California Contributor Information and Disclosures

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Overview Differential Diagnoses & Workup Treatment & Medication Follow-up

References Keywords Introduction
Background

The Rh factor (ie, Rhesus factor) is a red blood cell surface antigen that was named after the monkeys in which it was first discovered. Rh incompatibility, also known as Rh disease, is a condition that occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells, leading to the development of Rh antibodies. Rh incompatibility can occur by 2 main mechanisms. The most common type occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, 1 invasive obstetric procedures, or normal delivery. Rh incompatibility can also occur when an Rh-negative female receives an Rh-positive blood transfusion. In part, this is the reason that blood banks prefer using blood type "O negative" or "type O, Rh negative," as the universal donor type in emergency situations when there is no time to type and crossmatch blood. The most common cause of Rh incompatibility is exposure from an Rh-negative mother by Rh-positive fetal blood during pregnancy or delivery. As a consequence, blood from the fetal circulation may leak into the maternal circulation, and, after a significant exposure, sensitization occurs leading to maternal antibody production against the foreign Rh antigen. Once produced, maternal Rh immunoglobulin G (IgG) antibodies may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia. Although the Rh blood group systems consist of several antigens (eg, D, C, c, E, e), the D antigen is the most immunogenic; therefore, it most commonly is involved in Rh incompatibility. Recommendations for screening for Rh incompatibility are available from the US Preventive Services Task Force.2
Pathophysiology

The amount of fetal blood necessary to produce Rh incompatibility varies. In one study, less than 1 mL of Rh-positive blood was shown to sensitize volunteers with Rh-negative blood. Conversely, other studies have suggested that 30% of persons with Rh-negative blood never develop Rh incompatibility, even when challenged with large volumes of Rh-positive blood. Once sensitized, it takes approximately one month for Rh antibodies in the maternal circulation to equilibrate in the fetal circulation. In 90% of cases, sensitization occurs during delivery. Therefore, most firstborn infants with Rh-positive blood type are not affected because the short period from first exposure of Rh-positive fetal erythrocytes to the birth of the infant is insufficient to produce a significant maternal IgG antibody response.

The risk and severity of sensitization response increases with each subsequent pregnancy involving a fetus with Rh-positive blood. In women who are prone to Rh incompatibility, the second pregnancy with an Rhpositive fetus often produces a mildly anemic infant, whereas succeeding pregnancies produce more seriously affected infants who ultimately may die in utero from massive antibody-induced hemolytic anemia. Risk of sensitization depends largely upon the following 3 factors: 1. 2. 3. Volume of transplacental hemorrhage Extent of the maternal immune response Concurrent presence of ABO incompatibility

The incidence of Rh incompatibility in the Rh-negative mother who is also ABO incompatible is reduced dramatically to 1-2% and is believed to occur because the mother's serum contains antibodies against the ABO blood group of the fetus. The few fetal red blood cells that are mixed with the maternal circulation are destroyed before Rh sensitization can proceed to a significant extent. Fortunately, ABO incompatibility usually does not cause serious sequela. Rh incompatibility is only of medical concern for females who are pregnant or plan to have children in the future. Rh-positive antibodies circulating in the bloodstream of an Rh-negative woman otherwise have no adverse effects.
Frequency
United States

Only 15% of the population lack the Rh erythrocyte surface antigen and are considered Rh-negative. The vast majority (85%) of individuals are considered Rh positive. Rh sensitization occurs in approximately 1 per 1000 births to women who are Rh negative. The Southwest United States has an incidence approximately 1.5 times the national average, which likely is caused by immigration factors and limited access to medical care since blood typing is a routine part of prenatal care. Even so, only 17% of pregnant women with Rh-negative blood who are exposed to Rh-positive fetal blood cells ever develop Rh antibodies.
Mortality/Morbidity

During the course of Rh incompatibility, the fetus is primarily affected. The binding of maternal Rh antibodies produced after sensitization with fetal Rh-positive erythrocytes results in fetal autoimmune hemolysis. As a consequence, large amounts of bilirubin are produced from the breakdown of fetal hemoglobin and are transferred via the placenta to the mother where they are subsequently conjugated and excreted by the mother. However, once delivered, low levels of glucuronyl transferase in the infant preclude the conjugation of large amounts of bilirubin and may result in dangerously elevated levels of serum bilirubin and severe jaundice.

Mildly affected infants may have little or no anemia and may exhibit only hyperbilirubinemia secondary to the continuing hemolytic effect of Rh antibodies that have crossed the placenta. Moderately affected infants may have a combination of anemia and hyperbilirubinemia/jaundice. In severe cases of fetal hyperbilirubinemia, kernicterus develops. Kernicterus is a neurologic syndrome caused by deposition of bilirubin into central nervous system tissues. Kernicterus usually occurs several days after delivery and is characterized by loss of the Moro (ie, startle) reflex, posturing, poor feeding, inactivity, a bulging fontanelle, a high-pitched shrill cry, and seizures. Infants who survive kernicterus may go on to develop hypotonia, hearing loss, and mental retardation. Another serious life-threatening condition observed in infants affected by Rh incompatibility is erythroblastosis fetalis, which is characterized by severe hemolytic anemia and jaundice. The most severe form of erythroblastosis fetalis is hydrops fetalis, which is characterized by high output cardiac failure, edema, ascites, pericardial effusion, and extramedullary hematopoiesis. Newborns with hydrops fetalis are extremely pale with hematocrits usually less than 5. Hydrops fetalis often results in death of the infant shortly before or after delivery and requires an emergent exchange transfusion if there is to be any chance of infant survival.

Race

Approximately 15-20% of Caucasians, as opposed to 5-10% of African Americans, have the Rhnegative blood type. Among individuals of Chinese and American Indian descent, the incidence of Rh-negative blood

type is less than 5%. Clinical

History

History of prior blood transfusion Rh blood type of the mother Rh blood type of the father (55% of Rh-positive men are genetically heterozygous for the Rh antigen and, therefore, produce Rh-negative offspring when mating with Rh-negative women 50% of the time.) Previous pregnancies, including spontaneous and elective abortions Previous administration of Rh IgG (RhoGAM) Mechanism of injury in cases of maternal trauma during pregnancy Presence of vaginal bleeding and/or amniotic discharge Previous invasive obstetric procedures, such as amniocentesis, cordocentesis, chorionic villous sampling, or ectopic pregnancy Note that a large fetal-maternal hemorrhage may occur without symptoms and with little or no evidence of trauma. Therefore, a high index of suspicion is warranted and a low threshold for treatment is indicated.

Physical

Evaluation of the vital signs and primary survey of the airway and cardiovascular system are indicated to ensure maternal stability. A thorough pelvic examination is required. In situations in which abdominal and/or pelvic trauma is a consideration, inspect for evidence of bruising that may suggest the possibility of significant fetomaternal hemorrhage. When an infant with an Rh-negative mother is delivered in the emergency department, a thorough physical examination of the infant must be performed after initial stabilization, and a neonatal clinician must be consulted immediately. Physical findings may vary from mild jaundice to extreme pallor and anemia with hydrops fetalis.

Causes

Factors that influence an Rh-negative pregnant female's chances of developing Rh incompatibility include the following:

Medscape

Ectopic pregnancy Placenta previa Placental abruption Abdominal/pelvic trauma In utero fetal death Any invasive obstetric procedure (eg, amniocentesis) Lack of prenatal care
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eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology

Rh Incompatibility: Differential Diagnoses & Workup

Author: Leon Salem, MD, MS, Associate Attending Physician, Kaiser Permanente, Southern California Coauthor(s): Karen R Singer, PA-C, Department of Pediatrics, Fountain Valley Medical Center, South Counties Pediatric Critical Care Medical Group, Fountain Valley and Long Beach, California Contributor Information and Disclosures Updated: Nov 4, 2009

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Overview Differential Diagnoses & Workup Treatment & Medication Follow-up

References Keywords Differential Diagnoses
Other Problems to Be Considered

ABO incompatibility Autoimmune hemolytic anemia Microangiopathic hemolytic anemia Spherocytosis Hereditary enzyme deficiencies Alpha thalassemia Chronic fetomaternal hemorrhage Twin-twin transfusion Erythroblastosis fetalis Hydrops fetalis Workup
Laboratory Studies

Prenatal emergency care

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Determination of Rh blood type is required in every pregnant female. In a pregnant woman with Rh-negative blood type, the Rosette screening test often is the first test performed. The Rosette test can detect alloimmunization caused by very small amounts of fetomaternal hemorrhage. When a high clinical suspicion of large fetomaternal hemorrhage is present (>30 mL blood), the Kleihauer-Betke acid elution test often is performed. The Kleihauer-Betke test is a quantitative measurement of fetal red blood cells in maternal blood, and it can be valuable for determining if additional amounts of Rh IgG should be administered. The amount of Rh IgG required for treatment after sensitization is at least 20 mcg/mL of fetal RBCs.

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Point-of-care blood tests have become available for use in the emergency department and have been shown to have very high sensitivity and specificity in determining Rh status. 3 Obtaining maternal Rh antibody titers can be helpful for future follow-up care of pregnant females who are known to be Rh negative and may be initiated from the ED. High levels of maternal Rh antibodies suggest that Rh sensitization has occurred, and further studies, such as amniocentesis and/or cordocentesis, may be necessary to evaluate the health of the fetus.

Postnatal emergency care

Immediately after the birth of any infant with an Rh-negative mother in the ED or prehospital setting, examine blood from the umbilical cord of the infant for ABO blood group and Rh type, measure hematocrit and hemoglobin levels, perform a serum bilirubin analysis, obtain a blood smear, and perform a direct Coombs test. A positive direct Coombs test result confirms the diagnosis of antibody-induced hemolytic anemia, which suggests the presence of ABO or Rh incompatibility. Elevated serum bilirubin measurements, low hematocrit, and elevated reticulocyte count from the neonate can help determine if an early exchange transfusion is necessary. An emergent exchange transfusion, preferably performed in a neonatal intensive care setting with experience in this procedure, is required in infants born with erythroblastosis fetalis, hydrops fetalis, or kernicterus.

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Imaging Studies

In the ED, ultrasonography of a pregnant female with suspected Rh incompatibility is limited to pelvic ultrasonography.

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Other Tests

Fetal ascites and soft tissue edema are definite signs of severe involvement. Once hydrops fetalis has developed, the sonographic evidence includes scalp edema, cardiomegaly, hepatomegaly, pleural effusion, and ascites.

Perform fetal monitoring in cases of suspected fetal distress. Abnormal fetal heart tones and ultrasonographic evidence of fetal or placental injury are indications of worsening fetal condition requiring emergent delivery, ideally in a center specializing in high-risk obstetric care.

eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology

Rh Incompatibility: Treatment & Medication

Author: Leon Salem, MD, MS, Associate Attending Physician, Kaiser Permanente, Southern California Coauthor(s): Karen R Singer, PA-C, Department of Pediatrics, Fountain Valley Medical Center, South Counties Pediatric Critical Care Medical Group, Fountain Valley and Long Beach, California Contributor Information and Disclosures Updated: Nov 4, 2009

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Overview Differential Diagnoses & Workup Treatment & Medication Follow-up

References Keywords Treatment
Prehospital Care

When possible, prehospital care personnel should direct their efforts on stabilization of the mother and infant, followed by immediate transport to a facility specializing in high-risk obstetric and neonatal care.
Emergency Department Care

ED care of the pregnant woman with Rh-negative blood and a suspected fetomaternal hemorrhage varies depending on the presentation of the patient and the gestational age of the fetus. If the mother has Rh-negative blood and has not been sensitized previously, administer human anti-D immune globulin (Rh IgG or RhoGAM) and refer the woman for further evaluation. If the mother has been sensitized previously, as determined by elevated level of maternal Rh antibodies, administration of Rh IgG is of no value. In this situation, prompt referral to a center that specializes in high-risk obstetrics is warranted. When an infant with Rh incompatibility is delivered in the ED, a more aggressive approach is required, centering on respiratory and hemodynamic stabilization of the infant and determining the need for an emergent exchange transfusion and phototherapy.

Consultations

Refer every pregnant female with Rh incompatibility to a medical center specializing in high-risk obstetric care. Medication Rh IgG, first released for general use in 1968, has been remarkably successful in the prevention of Rh incompatibility. In the Rh-negative mother, the preparation is administered after a suspected fetomaternal hemorrhage. The exact mechanism by which passive administration of Rh IgG prevents Rh immunization is unknown. The most likely hypothesis is that the Rh immune globulin coats the surface of fetal RBCs containing Rh antigens. These exogenous antibody-antigen complexes cross the placenta before they can stimulate the maternal endogenous immune system B cells to produce IgG antibodies. Since Rh IgG became the standard of care in the United States, the risk of Rh incompatibility has been reduced from 10-20% to less than 1%. Because of its short half-life, Rh IgG routinely is administered once at 28-32 weeks' gestation and again within 72 hours after birth to all Rh-negative pregnant females as a part of routine prenatal care. The current recommendation is that every Rh-negative nonimmunized woman who presents to the ED with antepartum bleeding or potential fetomaternal hemorrhage should receive 300 mcg of Rh IgG IM. For every 30 mL of fetal whole blood exposed to maternal circulation, 300 mcg of Rh IgG should be administered. A lower 50-mcg dose preparation of Rh IgG is available and recommended for Rh-negative females who have termination of pregnancy in the first trimester when fetomaternal hemorrhage is believed to be minimal.
Blood derived product

This agent is effective in preventing Rh isoimmunization.

Human anti-D immune globulin (RhoGAM, BayRho-D, Rhophylac, HyperRho)

Suppresses immune response of nonsensitized Rh O (D) negative mothers exposed to Rh O (D) positive blood from the fetus as a result of a fetomaternal hemorrhage, abdominal trauma, amniocentesis, abortion, full-term delivery, or transfusion accident. Should be administered if the patient is Rh negative, unless the father also is Rh negative.
Dosing Interactions Contraindications Precautions

Adult

RhoGAM, BayRho-D, HyperRho: <13 wk gestation: 50 mcg IM >13 wk gestation: 300 mcg IM Rhophylac: 20 mcg/2 mL transfused blood or 20 mcg/mL erythrocyte concentrate administered IV/IM
Pediatric

Administer as in adults

eMedicine Specialties > Obstetrics and Gynecology > Labor and Delivery

Abnormal Labor
Updated: Aug 3, 2009

Author: Saju Joy, MD, MS, Assistant Professor, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Wake Forest University School of Medicine Coauthor(s): Patricia L Scott, MD, Fellow in Maternal-Fetal Medicine, Wake Forest University, Bowman Gray School of Medicine; Deborah Lyon, MD, Director, Division of Gynecology, Associate Professor, Department of Obstetrics and Gynecology, University of Florida Health Science Center at Jacksonville Contributor Information and Disclosures

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Overview Differential Diagnoses & Workup Treatment & Medication Follow-up Multimedia
References Keywords Introduction
Background

To define abnormal labor, a definition of normal labor must be understood and accepted. Normal labor is defined as uterine contractions that result in progressive dilation and effacement of the cervix. By following thousands of labors resulting in uncomplicated vaginal deliveries, time limits and progress milestones have been identified that define normal labor. Failure to meet these milestones defines abnormal labor, which suggests an increased risk of an unfavorable outcome. Thus, abnormal labor alerts the obstetrician to consider alternative methods for a successful delivery that minimize risks to both the mother and the infant. Dystocia of labor is defined as difficult labor or abnormally slow progress of labor. Other terms that are often used interchangeably with dystocia are dysfunctional labor, failure to progress (lack of progressive cervical dilatation or lack of descent), and cephalopelvic disproportion (CPD). Friedman's original research in 1955 defined 3 stages of labor. 1

The first stage starts with uterine contractions leading to complete cervical dilation and is divided into latent and active phases. In the latent phase, irregular uterine contractions occur with slow and gradual cervical effacement and dilation. The active phase is demonstrated by an increased rate of cervical dilation and fetal descent. The active phase usually starts at 3-4 cm cervical dilation and is subdivided into the acceleration, maximum slope, and deceleration phases. The second stage of labor is defined as complete dilation of the cervix to the delivery of the infant. The third stage of labor involves delivery of the placenta.

See Media files 1-2 for the normal labor curves of both nulliparas and multiparas. The following table shows abnormal labor indicators.

Labor curve for nulliparas.

Labor curve for nulliparas versus multiparas.

[#targetTable#] Table. Abnormal Labor Indicators Open table in new window

Indication Prolonged latent phase Average second stage Prolonged second stage without (with) epidural Protracted dilation Protracted descent Arrest of dilation* Arrest of descent* Prolonged third stage Indication Prolonged latent phase Average second stage Prolonged second stage without (with) epidural Protracted dilation Protracted descent Arrest of dilation* Arrest of descent* Prolonged third stage Nullipara >20 h 50 min >2 h (>3 h) <1.2 cm/h <1 cm/h >2 h >2 h >30 min Nullipara >20 h 50 min >2 h (>3 h) <1.2 cm/h <1 cm/h >2 h >2 h >30 min Multipara >14 h 20 min >1 h (>2 h) <1.5 cm/h <2 cm/h >2 h >1 h >30 min Multipara >14 h 20 min >1 h (>2 h) <1.5 cm/h <2 cm/h >2 h >1 h >30 min

*Adequate contractions >200 Montevideo units [MVU] per 10 minutes for 2 hours. (Please refer to the Pathophysiology for information regarding adequate contractions.) Abnormal labor constitutes any findings that fall outside the accepted normal labor curve. However, the authors hesitate to apply the diagnosis of abnormal labor during the latent phase because it is easy to confuse prodromal contractions for latent labor. In addition, the original labor curve, as defined by Friedman, may not be completely applicable today. 2,3,4,5 First stage of labor Latent phase: Definitions for prolonged latent phase are outlined in the table above. Diagnosis of abnormal labor during the latent phase is uncommon and likely an incorrect diagnosis. Active phase: Around the time uterine contractions cause the cervix to become 3-4 cm dilated, the patient usually enters the active phase of the first stage of labor. Abnormalities of cervical dilation (protracted dilation and arrest of dilation) as well as descent abnormalities (protracted descent and arrest of descent) are outlined in the table above. In general, abnormal labor is the result of problems with one of the 3 P' s.

Passenger (infant size, fetal presentation [occiput anterior, posterior, or transverse]) Pelvis or passage (size, shape, and adequacy of the pelvis) Power (uterine contractility)

See Causes.
Pathophysiology

A prolonged latent phase may result from oversedation or from entering labor early with a thickened or uneffaced cervix. It may be misdiagnosed in the face of frequent prodromal contractions. Protraction of active labor is more easily diagnosed and is dependent upon the 3 P' s. The first P, the passenger, may produce abnormal labor because of the infant's size (eg, macrosomia) or from malpresentation. The second P, the pelvis, can cause abnormal labor because its contours may be too small or narrow to allow passage of the infant. Both the passenger and pelvis cause abnormal labor by a mechanical obstruction, referred to as mechanical dystocia.

With the third P, the power component, the frequency of uterine contraction may be adequate, but the intensity may be inadequate. Disruption of communication between adjacent segments of the uterus may also exist, resulting from surgical scarring, fibroids, or other conduction disruption. Whatever the cause, the contraction pattern fails to result in cervical effacement and dilation. This is called functional dystocia. Uterine contractile force can be quantified by the use of an intrauterine pressure catheter. Use of this device allows for direct measurement and calculation of uterine contractility per each contraction and is reported in Montevideo units (MVUs). For uterine contractile force to be considered adequate, the force produced must exceed 200 MVUs during a 10-minute contraction period. Arrest disorders cannot be properly diagnosed until the patient is in the active phase and had no cervical change for 2 or more hours with the contraction pattern exceeding 200 MVUs. Uterine contractions must be considered adequate to correctly diagnose arrest of dilation. 6
Frequency
United States

Of all cephalic deliveries, 8-11% are complicated by an abnormal first stage of labor. Dystocia occurs in 12% of deliveries in women without a history of prior cesarean delivery. Dystocia may account for as many as 60% of cesarean deliveries.
Mortality/Morbidity

Both maternal and fetal mortality and morbidity rates increase with abnormal labor. This is probably an effect-effect relationship rather than a cause-effect relationship. Nonetheless, identification of abnormal labor and initiation of appropriate actions to reduce the risks are matters of some urgency. Clinical
History

Evaluate every pregnant patient who presents with contractions in the labor and delivery unit. Any patient in labor is at risk for abnormal labor regardless of the number of previous pregnancies or the seemingly adequate dimensions of the pelvis. Plot the progress of any patient in labor, and evaluate it on a labor curve (see Media files 1-2).

Labor curve for nulliparas.

Labor curve for nulliparas versus multiparas.

Physical

Upon admission to the labor and delivery unit, determine and document clinical findings.

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Causes

Clinical pelvimetry, which is best performed at the first prenatal care visit, is important in order to assess the pelvic type (eg, android, gynecoid, platypelloid, anthropoid). Evaluate the position of the fetal head in early labor because caput and moulding complicate correct assessment as labor progresses. Establish and document an estimated fetal weight. Monitor fetal heart rate and uterine contraction patterns to assess fetal well-being and adequacy of labor. Perform a cervical examination to determine whether the patient is in the latent or active phase of labor.

Addressing these issues allows for an assessment of the current phase of labor and anticipation of whether abnormal labor from any of the 3 P' s may be encountered.

Prolonged latent phase: The latent phase of labor is defined as the period of time starting with the onset of regular uterine contractions and ending with the onset of the active phase (usually 3-4 cm cervical dilation).

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A prolonged latent phase is defined as exceeding 20 hours in patients who are nulliparas or 14 hours in patients who are multiparas. The most common reason for prolonged latent phase is entering labor without substantial cervical effacement.

Power: Power is defined as uterine contractility multiplied by the frequency of contractions.

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Montevideo units (MVUs) refer to the strength of contractions in millimeters of mercury multiplied by the frequency per 10 minutes as measured by intrauterine pressure transducer. The uterine contraction pattern should repeat every 2-3 minutes. The uterine contractile force produced must exceed 200 MVUs/10 min for active labor to be considered adequate. For example, 3 contractions in 10 minutes that each reach a peak of 60 mm Hg are 60 X 3 = 180 MVUs. An arrest disorder of labor cannot be diagnosed until the patient is in the active phase and the contraction pattern exceeds 200 MVUs for 2 or more hours with no cervical change. Extending the minimum period of oxytocin augmentation for active-phase arrest from 2 up to 4 hours may be considered as long as fetal reassurance is noted with fetal heart rate monitoring.

Pelvis or the size of the passageway inhibiting delivery

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The shape of the bony pelvis (eg, anthropoid or platypelloid) can result in abnormal labor. A patient who is extremely short or obese, or who has had prior severe trauma to the bony pelvis, may also be at increased risk of abnormal labor.

Abnormal labor could also be secondary to the passenger, the size of the infant, and/or the presentation of the infant.

In addition to problems caused by the differential in size between the fetal head and the maternal bony pelvis, the fetal presentation may include asynclitism or head extension. Asynclitism is malposition of the fetal head within the pelvis, which compromises the narrowest diameter through the pelvis. Fetal macrosomia and other anomalies (including hydrocephalus, encephalocele, fetal goiter, cystic hygroma, hydrops, or any other abnormality that increases the size of the infant) are likely to cause deviation from the normal labor curve.

Other factors include either a low-dose epidural or combined spinal-epidural anesthetics that minimize motor block and may contribute to a prolonged second stage. These have also been associated with an increase in oxytocin use and operative vaginal delivery. However, use of epidural for analgesia during labor does not result in a statistically significant increase in cesarean delivery.7 Intravenous oversedation has also been implicated as prolonging labor in both the latent and active phases.