Recommendations for Pregnancy in Rare Inherited Anemias

Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defined. Moreover, during the last decade there has been a lack of proper understanding of the impact of rare anemias on maternal and fetal outcomes. In addition, there are no clear-cut guidelines outlining the pathophysiological trends and management options unique to this special population. Here, we present on behalf of the European Hematology Association, evidence- and consensus-based guidelines, established by an international group of experts in different fields, including hematologists, gynecologists, general practitioners, medical geneticists, and experts in rare inherited anemias from various European countries for standardized and appropriate choice of therapeutic interventions for the management of pregnancy in rare inherited anemias, including Diamond-Blackfan Anemia, Congenital Dyserythropoietic Anemias, Thalassemia, Sickle Cell Disease, Enzyme deficiency and Red cell membrane disorders

Selective Use of Recombinant Human Erythropoietin in Pregnant Patients with Severe Anemia or Nonresponsive to Iron Sucrose Alone

Objective: To evaluate the effectiveness of a stepwise use of recombinant human erythropoietin (rhEPO) in pregnant patients with severe anemia or nonresponsive to intravenously administered iron only. Methods: All subjects had iron deficiency anemia, i.e., a hemoglobin (Hb) level /=9.0 g/dl and <10.0 g/dl received 200 mg iron sucrose intravenously twice weekly. If response to therapy was poor, patients additionally received 10,000 U rhEPO twice weekly. Patients with an Hb level <9.0 g/dl primarily received iron sucrose and rhEPO likewise. Results: Of the 84 patients, 59 had a baseline Hb level between 9.0 and 9.9 g/dl, of whom 32 responded poorly, thus receiving additional rhEPO. Twenty-five patients had a baseline Hb level <9.0 g/dl. The overall Hb level after therapy was 11.0 g/dl (+/-0.5, range 10.0-12.6 g/dl). Mean duration of therapy was 3.5 weeks (7 infusions). Conclusion: This study shows an effective treatment regimen for patients with various degrees of anemia in pregnancy. Iron sucrose is a safe and effective treatment option. In cases of severe iron deficiency anemia or poor response to parenteral iron therapy additional administration of rhEPO might be considered. However, the mechanism for not responding to intravenous iron therapy despite iron deficiency anemia still remains unclear to a large extent

Mild anemia and pregnancy outcome in a Swiss collective

Background. Over half of all women in the world experience anemia during their pregnancy. Our aim was to investigate the relation between hemoglobin and iron status examined in second trimester and pregnancy outcome. Methods. In a prospective longitudinal study, 382 pregnant women were included. Blood samples were examined for hematological status and serum ferritin between 16 and 20 weeks and for hemoglobin before delivery. The adverse maternal and perinatal outcomes were determined. Regression analysis was performed to establish if anemia and low serum ferritin are risk factors for pregnancy complications. Results. There was no increase of complications in women with mild anemia and in women with depleted iron stores. The finding showed that mild iron deficiency anemia and depleted iron stores are not risk factors for adverse outcomes in iron supplemented women. Conclusions. Mild anemia and depleted iron stores detected early in pregnancy were not associated with adverse maternal and perinatal outcomes in iron supplemented women

Anemia - prevalence and risk factors in pregnancy

BACKGROUND: To assess the prevalence of decreased iron stores and anemia in pregnant women. To determine whether the risk factors: socio-demographic background, age, BMI, and parity are associated with abnormal hemoglobin concentrations and/or abnormal iron status. METHODS: A longitudinal study was carried out at the Department of Obstetrics, University Hospital of Zurich to establish the risk factors and prevalence of the decreased iron stores and anemia in early pregnancy. In order to determine the hematological parameters and ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and 20 pregnancy weeks were collected. According to hemoglobin and iron status, the patients were divided into four groups: patients with iron deficiency anemia, patients with decreased iron stores, patients with anemia for other reasons and normal patients. The determinants socio-demographic background, age, BMI and parity were explored using multiple logistic regression analysis. RESULTS: The prevalence of decreased iron stores (ferritin<20 μg/l) was observed in 31.8% of subjects (149/470) and anemia (Hb<110 g/l) in 18.5% (87/470). The prevalence of iron deficiency anemia was higher among women coming from former Yugoslavia and developing countries (p=0.004 and p=0.012). In patients coming from developing countries, a significant increase of anemia for other reasons was observed (p=0.027) and in patients older than 30 years, a significant increase of decreased iron stores (p=0.018). CONCLUSIONS: In our study population with low parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2% (236/470), and socio-demographic background was the most important risk factor of anemia

Abnormal placental invasion experience at 1 center

OBJECTIVE: To identify the incidence, risk factors, and maternal and neonatal outcome of pregnancies with abnormal placentation at a single center. STUDY DESIGN: A retrospective review of the medical records of the deliveries in 1999-2003 at the Department of Obstetrics, University Hospital Zurich, was conducted with respect to abnormal placentation, and the incidence, risk factors and outcomes were observed. RESULTS: Thirty-one women with abnormal placentation were identified. They represented 0.31% of deliveries during the 5-year period. The significant factors associated with abnormal placentation were previous uterine curettage (OR = 19.3, 95% CI 11.6-32.3), previous uterine surgery other than cesarean sections (OR = 49.6, 95% CI 24.3-102.3) and coexistent placenta previa (OR = 16.1, 95% CI 4.7-43.7). No case of maternal death occurred, and 1 neonatal death due to uterine rupture occurred in the study group. CONCLUSION: The most important risk factor in abnormal placentation was a previous uterine intervention

Red blood cell parameters in antenatal nonsickling hemoglobinopathy screening

Gabriela Bencaiova, Kristina Dapoto, Roland Zimmermann, Alexander Krafft Department of Obstetrics and&nbsp;Gynecology, Institute of Obstetric Research, University Hospital Zurich, Zurich, Switzerland Objective: To find a hematological parameter and the cut-off level for identification of nonsickling hemoglobinopathies in pregnant women. Materials and methods: Venous blood samples of 849 women with singleton pregnancies were collected at the first visit. All women who met inclusion criteria were examined for nonsickling hemoglobinopathy. On the basis of the sensitivity and the specificity of different cut-off levels for hematological parameters, we calculated the optimal clinically practicable parameter for screening of nonsickling hemoglobinopathies in pregnant women. Results: On the basis of the sensitivity and the specificity, the best screening parameters for the identification of nonsickling hemoglobinopathies among nonanemic pregnant women are mean corpuscular volume (MCV) with cut-off &le;80&nbsp;fL (Youden&rsquo;s index 91.2%), mean corpuscular hemoglobin (MCH) &lt;27.5&nbsp;pg (Youden&rsquo;s index 90.7%), and microcytosis (MRC) &ge;3% (Youden&rsquo;s index 90.2%). An analysis using receiver operating characteristic curves and the calculated Youden&rsquo;s index showed that MCV &le;76&nbsp;fL, MCH &le;24&nbsp;pg, or MRC &ge;10% are the best red blood cell indices for the screening of nonsickling hemoglobinopathy among anemic women with iron deficiency. Conclusion: Our results suggest targeted screening for nonsickling hemoglobinopathies in nonanemic pregnant women with MCV &le;80&nbsp;fL, MCH &le;27.5&nbsp;pg, or MRC &ge;3% and in anemic women with MCV &le;76&nbsp;fL, MCH &le;24&nbsp;pg, or MRC &ge;10%. Keywords: anemia, antenatal, hemoglobinopathy, pregnancy, screening, hemoglobin, hematological parameter

Iron prophylaxis in pregnancy: Intravenous route versus oral route

OBJECTIVE: To assess and compare the efficacy and safety of two and three doses of intravenous iron sucrose with daily oral ferrous sulphate in the prophylaxis of iron deficiency anaemia in pregnant women. STUDY DESIGN: 260 women with singleton pregnancy who met inclusion criteria and who gave informed consent were randomised between the 21st and 24th week into either the intravenous iron group or the oral iron group. Of 130 women in the intravenous iron group, 75 women received two doses of 200mg iron sucrose and 55 three doses of 200mg iron sucrose. The first dose was administered between the 21st and 24th gestational weeks, the second between the 28th and 32nd and the third between the 35th and 37th. The women of the oral group were given oral tablets of 80 mg ferrous sulphate daily, beginning on the day of study enrolment and stopping on the day of delivery. RESULTS: There was a non-significant trend to a higher frequency of responders (haemoglobin> or =11 g/dl) in the intravenous iron group (75 vs. 80%). There was a significant difference of repleted iron stores before delivery (ferritin>50 microg/l) in the group with three intravenous iron doses in comparison to the oral iron group (49 vs. 14%; p<0.001). No differences were observed in regard to maternal and perinatal outcomes. CONCLUSIONS: There was no clinically significant difference in the haematological, maternal and foetal outcomes in the parenteral route of iron prophylaxis in pregnant women

Treatment of Anemia of Chronic Disease with True Iron Deficiency in Pregnancy

Objective. We assess and compare the efficacy of anemia treatment in pregnant women with anemia of chronic disease with true iron deficiency and in women with iron deficiency anemia. Study Design. Fifty patients with moderate anemia (hemoglobin 8.0–9.9 g/dl) and iron deficiency (ferritin < 15 μg/l) were treated in the Anemia Clinic at the Department of Obstetrics. Results. All patients showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte count at day eight of therapy and showed an increase in hemoglobin and hematocrit at the end of therapy (p<0.001). The target hemoglobin (≥10.5 g/dl) was achieved in 45/50 women (90%). 12 patients showed anemia of chronic disease with true iron deficiency (12/50; 24%). Seven women (7/12; 59%) with anemia of chronic disease and iron deficiency responded well to anemia treatment. 50% of women with anemia of chronic disease and iron deficiency (3/6) responded well to intravenous iron, and 67% (4/6) responded well to the combination of intravenous iron and recombinant human erythropoietin. Conclusion. Because of frequent true iron deficiency in pregnant women with anemia of chronic disease, anemia of chronic disease in pregnancy is often falsely diagnosed as iron deficiency anemia