Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review.

Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), as well as weekly maternal IV immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy, are common options, but optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and 22 nonrandomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of the antenatal management strategy applied; FBS, IUPT, or IVIG with or without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. FBS or IUPT resulted in a relatively high complication rate (consisting mainly of preterm emergency cesarean section) of 11% per treated pregnancy in all studies combined. Overall, noninvasive management in pregnant mothers who have had a previous neonate with FNAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. This systematic review suggests that first-line antenatal management in FNAIT is weekly IVIG administration, with or without the addition of corticosteroids.

[1]  G. Bein,et al.  Antiendothelial &agr;v&bgr;3 Antibodies Are a Major Cause of Intracranial Bleeding in Fetal/Neonatal Alloimmune Thrombocytopenia , 2016, Arteriosclerosis, thrombosis, and vascular biology.

[2]  E. Lopriore,et al.  Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature , 2016, Transfusion.

[3]  K. Rossi,et al.  Effects of antepartum therapy for fetal alloimmune thrombocytopenia on maternal lifestyle , 2015, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[4]  J. Bussel,et al.  Suppression of in vitro megakaryopoiesis by maternal sera containing anti-HPA-1a antibodies. , 2015, Blood.

[5]  E. Lopriore,et al.  Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial , 2015, Fetal Diagnosis and Therapy.

[6]  J. Freedman,et al.  Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. , 2015, The Journal of clinical investigation.

[7]  F. Walther,et al.  Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin. , 2015, Blood transfusion = Trasfusione del sangue.

[8]  P. Tugwell,et al.  The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses , 2014 .

[9]  R. Marcos,et al.  The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies. , 2013 .

[10]  A. David,et al.  Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry , 2013, BMJ Open.

[11]  Jonathan J Deeks,et al.  Issues relating to study design and risk of bias when including non‐randomized studies in systematic reviews on the effects of interventions , 2013, Research synthesis methods.

[12]  M. Carneiro-Sampaio,et al.  IgG Placental Transfer in Healthy and Pathological Pregnancies , 2011, Clinical & developmental immunology.

[13]  P. Cherin,et al.  Relevant Criteria for Selecting an Intravenous Immunoglobulin Preparation for Clinical Use , 2010, BioDrugs.

[14]  M. Dramé,et al.  Prediction of the fetal status in noninvasive management of alloimmune thrombocytopenia. , 2011, Blood.

[15]  Y. Ville,et al.  Fetal alloimmune thrombocytopenia: is less invasive antenatal management safe? , 2011, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[16]  B. Tutschek,et al.  Repeated intrauterine IgG infusions in foetal alloimmune thrombocytopenia do not increase foetal platelet counts , 2010, Vox sanguinis.

[17]  Michele Tarsilla Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[18]  R. Berkowitz,et al.  Intracranial hemorrhage in alloimmune thrombocytopenia: stratified management to prevent recurrence in the subsequent affected fetus. , 2009, American journal of obstetrics and gynecology.

[19]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[20]  P. Hordijk,et al.  HPA-1a alloantibodies reduce endothelial cell spreading and monolayer integrity. , 2009, Molecular immunology.

[21]  D. Altman,et al.  Chapter 8: Assessing risk of bias in included studies , 2008 .

[22]  D. Altman,et al.  Assessing Risk of Bias in Included Studies , 2008 .

[23]  R. Berkowitz,et al.  Antepartum Treatment Without Early Cordocentesis for Standard-Risk Alloimmune Thrombocytopenia: A Randomized Controlled Trial , 2007, Obstetrics and gynecology.

[24]  W. Ouwehand,et al.  Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia , 2007, Transfusion.

[25]  E. Lopriore,et al.  Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective , 2007, BJOG : an international journal of obstetrics and gynaecology.

[26]  F. Walther,et al.  Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG , 2007, European Journal of Pediatrics.

[27]  E. Schiff,et al.  Antenatal noninvasive treatment of patients at risk for alloimmune thrombocytopenia without a history of intracranial hemorrhage. , 2006, American journal of obstetrics and gynecology.

[28]  V. Jallu,et al.  Predictive value of sequential maternal anti‐HPA‐1a antibody concentrations for the severity of fetal alloimmune thrombocytopenia , 2006, Journal of thrombosis and haemostasis : JTH.

[29]  R. Berkowitz,et al.  Parallel Randomized Trials of Risk-Based Therapy for Fetal Alloimmune Thrombocytopenia , 2006, Obstetrics and gynecology.

[30]  F. Walther,et al.  Intravenous Immunoglobulins without Initial and Follow-Up Cordocentesis in Alloimmune Fetal and Neonatal Thrombocytopenia at High Risk for Intracranial Hemorrhage , 2005, Fetal Diagnosis and Therapy.

[31]  S. Brunskill,et al.  Antenatal interventions for fetomaternal alloimmune thrombocytopenia. , 2005, The Cochrane database of systematic reviews.

[32]  A. Brand,et al.  Follow up of children after antenatal treatment for alloimmune thrombocytopenia. , 2004, Early human development.

[33]  R. Aster,et al.  Human platelet antigen‐specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia , 2004, Transfusion.

[34]  M. Westgren,et al.  Experiences with fetomaternal alloimmune thrombocytopenia at a Swedish hospital over a 10‐year period , 2003, Acta obstetricia et gynecologica Scandinavica.

[35]  H. Kroll,et al.  European collaborative study of the antenatal management of feto‐maternal alloimmune thrombocytopenia , 2003, British journal of haematology.

[36]  A. Brand,et al.  Will it ever be possible to balance the risk of intracranial haemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it? , 2003, Vox sanguinis.

[37]  N. Fisk,et al.  Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome. , 2002, American journal of obstetrics and gynecology.

[38]  A. Brand,et al.  A less invasive treatment strategy to prevent intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia. , 2001, American journal of obstetrics and gynecology.

[39]  T. Porter,et al.  Neonatal alloimmune thrombocytopenia: antenatal management. , 2000, American journal of obstetrics and gynecology.

[40]  Teramo,et al.  Prenatal treatment of severe fetomaternal alloimmune thrombocytopenia , 1999, Transfusion medicine.

[41]  Kaplan,et al.  Feto‐maternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids — more questions than answers , 1998, British journal of haematology.

[42]  D. Farquharson,et al.  Antenatal invasive and noninvasive management of alloimmune thrombocytopenia. , 1996, Fetal diagnosis and therapy.

[43]  R. Berkowitz,et al.  Antenatal management of alloimmune thrombocytopenia with intravenous γ-globulin: A randomized trial of the addition of low-dose steroid to intravenous γ-globulin. , 1996, American journal of obstetrics and gynecology.

[44]  R. Berkowitz,et al.  Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. , 1996, American journal of obstetrics and gynecology.

[45]  R. Berkowitz,et al.  Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis. , 1995, American journal of obstetrics and gynecology.

[46]  K. Nicolaides,et al.  Antenatal management of fetomaternal alloimmune thrombocytopenia—report of 15 affected pregnancies , 1994, Transfusion medicine.

[47]  R. Williamson,et al.  Antenatal Treatment of Fetal Alloimmune Thrombocytopenia , 1992, Obstetrics and gynecology.

[48]  R. Berkowitz,et al.  Antenatal Treatment of Alloimmune Thrombocytopenia , 1992, Obstetrics and gynecology.

[49]  G. Mueller‐Eckhardt,et al.  348 CASES OF SUSPECTED NEONATAL ALLOIMMUNE THROMBOCYTOPENIA , 1989, The Lancet.

[50]  C. Kaplan,et al.  Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. , 1989, Blood.

[51]  R. Berkowitz,et al.  Antenatal treatment of neonatal alloimmune thrombocytopenia. , 1988, The New England journal of medicine.

[52]  J. Herman,et al.  In utero cerebral hemorrhage in alloimmune thrombocytopenia. , 1986, The American journal of pediatric hematology/oncology.

[53]  F. Daffos,et al.  PRENATAL TREATMENT OF ALLOIMMUNE THROMBOCYTOPENIA , 1984, The Lancet.

[54]  A. Basten,et al.  Immune Complexes in Thrombocytopenic Patients: Cause or Effect? , 1980, British journal of haematology.

[55]  Leighton Da Letter: Wound infection in acute appendicitis. , 1974, Lancet.