Recommendations for the prevention and treatment of haemolytic disease of the foetus and newborn.

Recommendations for the prevention and treatment of haemolytic disease of the foetus and newborn Bennardello, 1 Serelina Coluzzi, 2 Giuseppe Curciarello, 3 Tullia Todros, 4 and Stefania Villa5, as Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) and Italian Society of Gynaecology and Obstetrics (SIGO) working group information Copyright and License information Disclaimer article has been cited by other articles in PMC. to: publication of the second edition of the “Recommendations for the prevention and treatment of haemolytic disease of the foetus and newborn” is the result of collaboration between the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI, Società Italiana di Medicina Trasfusionale e Immunoematologia) and the Italian Society of Gynaecology and Obstetrics (SIGO, Società Italiana di Ginecologia e Ostetricia). recommendations published in 20061 have been revised in the light of current scientific evidence: the immunohaematological and instrumental investigations that should be performed in the antenatal and perinatal periods, the immunoprophylaxis (IP) to prevent the haemolytic disease of the foetus and newborn (HDFN due to RhD incompatibility and the treatment to use if HDFN develops are described. recommendations are focused on the prevention and management of HDFN, in particular that one due to RhD incompatibility, the most serious form of this condition. Although IP has dramatically reduced the number of cases of HDFN, this disease continues to occur and engage specialists in Transfusion Medicine, Obstetrics and Neonatology. The recommendations are aimed at Transfusion Structures (TS) and all public facilities pertaining to Mother and Child Departments, Family Planning Clinics and private structures managing pregnancies, including those in which the woman gives birth at home. The prevention of HDFN must be guaranteed, through organisational models adapted to local circumstances, to all pregnant women for whom it is deemed necessary and the women must also be ensured adequate information. HDFN due to RhD incompatibility, the recommendations also cover less frequent forms of the disease, caused by immunisation to other blood group antigens, and by ABO incompatibility, which is a more frequent laboratory finding, although of less importance from a clinical point of view. recommendations will be periodically reviewed in the light of evolving scientific knowledge, technology and clinical practice. They were developed on the basis of an analysis of current scientific literature (identified through bibliographic searches of Medline/PubMed and Ovid databases) and were submitted to the consensus of experts from SIMTI and SIGO. Protocols jointly agreed upon by the Transfusion Medicine and Immunohaematology Services (SIMT, Servizio di Immunoematologia e Medicina Trasfusionale) and Obstetricians-Gynaecologists working in the same territory, including at a regional level, should be drawn up to promote compliance among pregnant women. to: of the recommendations purpose of this document is to give correct guidance on the management and prevention of HDFN with the aim of promoting homogeneous practices throughout Italy, ensuring a minimum common denominator of quality that can be achieved in all health care structures2 used by pregnant women or females of childbearing potential*. dual value of these recommendations is that besides being a technical and scientific support for doctors making clinical decisions regarding the management of HDFN, they also provide updates on the risks associated with immunisation in females of childbearing potential. recommendations are not intended in any way to replace either the physician’s clinical evaluation of individual cases or the doctor’s personal experience; they are, rather, a reference tool that can also be used to check the correctness of treatment. The final decision on a given treatment must always be taken by the doctor in the light of the clinical picture and resources available; however, substantial deviations from these recommendations should be documented and justified in the patient’s clinical records. For this purpose specific indicators for monitoring and evaluation have been identified to use in clinical audits. to: benefits expected benefits of the dissemination of these recommendations for the prevention and management of HDFN are as follows: - a decrease in the incidence of HDFN; - a decrease in the incidence of alloimmunisation; - an increase in appropriate clinical use of blood components in the foetal and neonatal periods; - an increase in the appropriate clinical use of blood components in females of childbearing potential; - an increase in the appropriate clinical use and dosages of anti-D immunoglobulin (Ig) ; - greater involvement of patients in decisions related to the prevention and management of HDFN. to: users of the recommendations and healthcare workers involved in the prevention, diagnosis and treatment of HDFN. to: recommendations are applicable to females of childbearing potential, pregnant women at risk of HDFN and foetuses/neonates affected by haemolytic disease caused by materno-foetal alloimmunisation. to: of the Working Group and grades of recommendation process of developing these recommendations, in accordance with the indications contained in the methodology manual of the National Guidelines Programme3, was based on systematic reviews of the literature and updating of already existing recommendations on the subject. For most of the recommendations there is an explicit evaluation of the quality of the proof leading to the recommendation and the strength with which the recommendation is made. In the absence of clear proof, the recommendations are based on a consensus of published opinions of experts and that of the Working Group. methodology used to derive the grades of recommendation was based on that used by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group4–6. According to the GRADE system, recommendations are classified by grades, expressed in Arabic numbers (1, 2), depending on their strength, and by letters (A, B, C) depending on the quality and type of evidence provided by the studies on which the recommendations are based. detail: - Grade 1: the authors are confident that the benefits for health clearly outweigh the undesirable effects, in terms of both risk and economic cost. This is, therefore, a strong recommendation. - Grade 2: the authors are less certain and the difference between desirable and undesirable effects is less clear. This is, therefore, a weak recommendation. to the quality and type of evidence provided by the studies in support of the recommendations, there are three levels of classification: - Grade A: high level of evidence. evidence derives from the analysis of numerous, substantial randomised studies without major limitations. It is unlikely that further research would alter the conclusions reached by these studies. - Grade B: moderate level of evidence. evidence is derived from randomised clinical trials but with important limitations (for example, inconsistent results, wide confidence intervals, methodological problems). Grade B is also attributed to recommendations derived from strong evidence collected in observational studies or case series (for example, treatment effects or the demonstration of a dose-response effect). Further research could change the conclusions of these studies. - Grade C: low or very low level of evidence. evidence is derived from an analysis of observational clinical studies with less consistent results or from the clinical experience/opinions of experts. Further research is required to consolidate or change the conclusions presented. speaking, it can be assumed that for all recommendations other than Grade 1A the authors recognise that other interpretations of the available evidence and other “clinical policies” are reasonable. conventional classification of evidence is based on mathematical and statistical criteria, with the “strength” of the evidence being assigned, in order, to: meta-analyses, randomised controlled trials, retrospective analyses, prospective follow-ups, cross-sectional population studies, reviews, anecdotal reports. This is correct as far as regards strictly clinical studies, especially if they are investigations of therapies and focused on objective evaluations of outcome. , the recommendations in some fields are weak; in contrast, in other areas the availability of clinical studies carried out with rigorous methodology in large groups of subjects has enabled specific recommendations to be made with more confidence. was not always possible to use aggregate data from meta-analyses: these variables increase the margins for individual decisions by each doctor and for each patient. to transfusion support for HDFN in the antenatal and postnatal periods (intrauterine transfusion, exchange transfusion ET, neonatal transfusion), the fundamental principles taken from the “Recommendations for transfusion therapy in neonatology”7 and subsequent amendments are reported in the appendix. appendix also contains some recommendations to be follo