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Recommendations for Pregnancy in Rare Inherited Anemias Ali T HEMASPHERE-2020-0127; Total nos of Pages: 14; HEMASPHERE-2020-0127 Powered by EHA Guideline Article - Consensus based Recommendations for Pregnancy in Rare Inherited Anemias Ali T. Taher1, Achille Iolascon2,3, Charbel F. Matar1, Rayan Bou-Fakhredin1, Lucia de Franceschi4, Maria Domenica Cappellini5, Wilma Barcellini6, Roberta Russo2,3, Immacolata Andolfo2,3, Paul Tyan7, Beatrice Gulbis8, Yesim Aydinok9, Nicholas P. Anagnou10, Gabriela Amstad Bencaiova11, Hannah Tamary12, Patricia Aguilar Martinez13, Gianluca Forni14, Raffaele Vindigni15, on behalf of the EHA Scientific Working Group on “Red Cells, Iron” Correspondence: Ali T. Taher (e-mail: [email protected]). Abstract 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. 1Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon 2Department of Molecular Medicine and Medical Biotechnologies, University Recommendations for pregnancy in rare Federico II of Naples, Italy anemias 3CEINGE Advanced Biotechnologies, Naples, Italy 4Department of Medicine, Section of Internal Medicine, University of Verona, Questions: Policlinico GB Rossi, AOUI, Verona, Italy 5Department of Clinical Sciences and Community, University of Milan, IRCCS Ca’ 1. Why specific guidelines for pregnancy in RIAs? What Granda Foundation Maggiore Policlinico Hospital, Milan, Italy makes RIAs different from the most common con- 6 ’ Hematology Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore ditions of anemia in pregnancy? When does an RIA Policlinico, Milan, Italy 7Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics deviate from the standard guidelines for anemia in and Gynecology, University of North Carolina School of Medicine, Chapel Hill, pregnancy? North Carolina, USA Rare inherited anemias (RIA) are a subset of anemias 8 Departments of Clinical Chemistry and Molecular Genetics, Academic Hospital caused by a myriad of genetic defects in one of the stages Erasme, Free University of Brussels, Brussels, Belgium 9Department of Pediatric Hematology and Oncology, Ege University Hospital, of red blood cell (RBC) cellular component formation Izmir, Turkey or erythropoiesis. The result of those defects is 10Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical detrimental to the RBC integrity, and thus its lifespan Research Foundation of The Academy of Athens (BRFAA), Athens, Greece 11 or its production. Due to their rare prevalence, the full Department of Obstetrics and Antenatal Care, University Hospital Basel, Basel, spectrum of disease complications and multi-organ Switzerland fi 12Department of Pediatric Hematology-Oncology, Schneider Children’s Medical system damage remains ill-de ned. More importantly, Center of Israel, Petach Tikva, Israel less is known about RIA’s impact on growth, develop- 13Department of biological hematology, CHU de Montpellier, and Montpellier ment, and long-term morbidity. The significant medical University, Montpellier, France fi 14 advances made in the eld of benign hematology have Centro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, ’ ’ Genova, Italy resulted in near normalization of RIA s patients 15United Onlus – Federazione Italiana delle Thalassemie, Emoglobinopatie Rare e longevity. Thus, the incidence of pregnancy among Drepanocitosi, Ferrara, Italy. affected patients is steadily increasing. A better The authors have no conflicts of interest to disclose. understanding of the impact of such rare anemias on © Copyright 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on maternal and fetal outcomes and evidence-based behalf of the European Hematology Association. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial- management guidelines is of paramount importance. No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download 2. When should a pregnancy in an inherited anemia be and share the work provided it is properly cited. The work cannot be changed in considered at risk? any way or used commercially without permission from the journal. Pregnancy in RIA should always be considered high HemaSphere (2020) 4:4(e446). http://dx.doi.org/10.1097/HS9.0000000000000446. Received: 28 April 2020 / Accepted: 16 June 2020 risk regardless of underlying risk factors. All available 1 HEMASPHERE-2020-0127; Total nos of Pages: 14; HEMASPHERE-2020-0127 Taher et al Recommendations for Pregnancy in Rare Inherited Anemias data and case reports confirm the higher risk of NTDT should be on a prophylactic dose of anti- complications seen throughout pregnancy in individu- coagulation in peripartum als with RIA. These complications vary depending on Regular folic acid supplementation 800 to 1000mg the type of anemia, its severity in addition to the daily is recommended in all mothers to prevent predisposing pathophysiology of the disease. superimposed megaloblastic anemia 3. What should be addressed? Delivery modality should be discussed between the The approach that should be taken once a woman patient and her gynecologist viewing the risks and with RIA and her partner are planning a pregnancy complications that are possible to take place should be multidisciplinary with collaboration among Optimize patient for vaginal vs cesarean section (C/S the hematologist, gynecologist and geneticist. for high risk and poorly controlled patients) a. The hematologist: has a role in optimizing the 8. Special advice for the post-partum in RIAs? management of anemia, iron chelation, complica- Close monitoring should continue post-partum for at tions secondary to iron overload and anemia. least first month. Anemia should be monitored, and b. The gynecologist: has a role in addressing the risks of iron chelation might need to be resumed earlier in cases pregnancy on the mother along with the risk during with highly iron overloaded. Vitamin supplementation delivery. He should monitor fetal complications such such as Calcium and Vitamin D is highly recommended. as growth restriction, fetal distress or hydrops fetalis. 9. May a pregnancy help to suspect a diagnosis of RIA? 4. Should the genetic and clinical counseling be given In rare situations, such in subclinical RIA women together? may develop severe anemias during pregnancy and The geneticist has a role prior and during pregnancy become symptomatic putting her fetus at risk. Hence, in onset by explain risk of pregnancy and risks of having this case, clinicians should opt to manage these offspring with the disease mainly in particular genetic pregnancies same as the high-risk RIA pregnancies. disorders. This consultation must include also the In rare cases, pregnant women may have enhancement examination of the partner, searching for an inherited of their symptoms due to pregnancy which will cause red cell defects that could modify the expected delay in diagnosis and proper management of RIA. phenotype. Hence, genetic counselling should take place 10. When should iron be considered in RIAs during whenever inherited form of anemia is suspected based on pregnancy? the medical/family history of any of the partners. Iron supplementation is not recommended in RIA 5. When to consider prenatal diagnosis? pregnancies, unless there is documentation of true iron Prenatal workup should be initiated whenever deficiency through laboratory iron testing. On the other clinicians have a suspicion of an affected baby. This hand, many patients have iron overload due to multiple should be considered as early as possible once blood transfusions and require iron chelation. suspected. During pregnancy, close monitoring with 11. When should transfusion be considered in RIAs during regular fetal ultrasound can orient the clinicians on pregnancy? doing prenatal diagnosis. Maternal anemia, defined as Hb < 11.6g/dL during Especially in the case of dominant condition or when the the first trimester of pregnancy, or Hb < 9.7-9.5 g/dL partner is also affected with an inherited form of anemia. during the second and third trimester, affects 7.5% to 6. Which tests are useful planning a pregnancy in RIA? 8.6% of the population and is objectively proven to be Maternal workup should be done prior to pregnancy an independent risk factor for maternal and fetal to decrease risks of complications: morbidity during
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