Severe Neonatal Thrombocytopenia Research Articles

Identifying Pregnancies at Higher Risk for HPA-1a Alloimmunization and Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT): An International, Prospective, Natural History Study

Background and significance Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility of human platelet antigen (HPA) and subsequent maternal sensitization. When this occurs, fetal platelet production is impaired and platelet destruction accelerated. FNAIT is the platelet counterpart of Rhesus disease (RhD); however, FNAIT is rarer, more often occurs in first pregnancies, and alloimmunization may be detected as early as the 2nd trimester. Clinical presentation of FNAIT ranges from no/mild symptoms to severe thrombocytopenia and intracranial hemorrhage, which can take place in the second trimester and cause death or lifelong neurological impairment. Severe FNAIT outcomes impose substantial emotional and financial burden on affected families and healthcare systems. Among pregnant HPA-1a-negative women bearing an HPA-1a-positive fetus at risk of alloimmunization, ~27% carry the HLA-DRB3*01:01 gene variant, increasing sensitization risk ~25 fold and thus leading to much higher FNAIT risk. Screening for FNAIT in pregnancy is not routinely performed, unlike in RhD, resulting in failure to identify at-risk pregnancies prior to birth. To prevent severe FNAIT outcomes, we believe at-risk pregnancies must be identified very early in the second trimester, and prophylactic interventions started immediately. Current management of women with existing alloimmunization due to a prior FNAIT-affected pregnancy involves months of weekly antenatal intravenous immunoglobulin with or without steroid administration. Although fetal platelet counts often improve, this therapy is very burdensome to patients. Most data on FNAIT prevalence and risk are from Caucasian populations; studies in non-Caucasian populations have been too small to be informative. This is the first epidemiological study that seeks to identify HPA-1a-based FNAIT in a racially and ethnically diverse international population of pregnant women. Data to be tracked are: frequency of DRB3*0101 in HPA-1bb women; anti-HPA-1a alloimmunization; pregnancy outcomes; and neonatal thrombocytopenia. These data will provide a contemporary control population preceding future single-arm studies of a novel human anti-HPA-1a monoclonal antibody, RLYB212, in prophylaxis of maternal HPA-1a alloimmunization and FNAIT. The virtual elimination of RhD by screening of all pregnancies and administration of prophylaxis in at-risk cases remains one of the most significant medical advances ever achieved and provides a roadmap for FNAIT. Study design and methods Prospective, non-interventional, natural-history study assessing HPA-1a alloimmunization in pregnant women, conducted across multiple European centers in Norway, Netherlands, UK, and Germany, and in the USA. It will provide insights into anti-HPA-1a-mediated FNAIT risk and frequency among Caucasian and non-Caucasian pregnant women. Up to 30,000 women will be screened at gestational weeks 10-14 to enable early identification and follow-up of those women at higher alloimmunization risk, so that in the future, prophylaxis of the higher-risk women could be initiated. Informed consent will be requested for blood-sample collection at the 10-14 week visit for evaluation of FNAIT risk. Inclusion criteria Pregnant women aged ≥18 years Exclusion criteria Prior history of FNAIT or known HPA-1a alloimmunization Statistical methods Demographic, baseline characteristics and discrete variables will be summarized Primary objective To inform frequency of higher FNAIT risk among pregnant women of diverse racial and ethnic characteristics (all comers). (Figure) Secondary objectives Frequency of HPA-1a maternal alloimmunization at Weeks 10-14 postpartum in pregnant women at higher FNAIT risk and outcomes such as: - Spontaneous abortion: non-deliberate fetal death prior to 19 weeks of gestation - Elective abortion: deliberate termination of pregnancy at any time in gestation - Stillbirth: non-deliberate fetal death after 19 weeks of gestation - Premature birth: live birth prior to 37 completed weeks of gestation - Live births: ≥37 completed weeks of gestation Neonatal and severe neonatal thrombocytopenia: platelet count <150 × 10 9/L and <50 × 10 9/L, respectively, within 72 hours of birth Current status Enrolment for clinical-trial NCT05345561 is ongoing and expected to continue for ~3 years.

Neonatal Thrombocytopenia: Differing Characteristics of NAIT Versus Non-NAIT.

While neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe neonatal thrombocytopenia good clinical predictors are lacking. We analyzed cases of neonatal thrombocytopenia in Schneider Children's Medical Center of Israel to pinpoint qualifiers of NAIT (NAIT+) in comparison to non-NAIT (NAIT-) thrombocytopenia. Patient and maternal data were retrospectively collected on all thrombocytopenic newborns undergoing a workup for NAIT in our tertiary center between 2001 and 2016. Among 26 thrombocytopenic neonates, the mean nadir in NAIT+ patients (25×10 9 /L) was significantly lower than NAIT- patients (64×10 9 /L) ( P <0.001). 61.5% of NAIT+ infants required treatment compared with 23% of non-NAIT ( P =0.015). NAIT+ patients also required more therapeutic modalities than infants with NAIT- thrombocytopenia. Human platelet antigen (HPA)-1a and HPA-5b alloantibodies most frequently caused NAIT. In summary, thrombocytopenia in NAIT+ was significantly more severe compared with NAIT- and more likely to require treatment. In addition, despite the varied ethnic population in Israel, the HPA alloantibodies found in our population were most similar to those common in Western countries. In the absence of rigorous prenatal screening options, we suggest platelet counts below 40 to 50×10 9 /L in a healthy newborn be considered most suggestive for NAIT and warrant urgent NAIT-specific analysis.

Severe autoimmune thrombocytopenia in a neonate secondary to maternal immune thrombocytopenia: a case report

&lt;p&gt;Neonatal thrombocytopenia is one of the common haematological problems encountered in neonatal intensive care unit. Severe neonatal thrombocytopenia is defined as a platelet count &amp;lt;50×10&lt;sup&gt;3&lt;/sup&gt;/µl and is relatively uncommon. Based on the time-of-onset, neonatal thrombocytopenia can be categorized into early-onset (&amp;lt;72 h after birth) and late-onset (&amp;gt;72 h after birth) thrombocytopenia. Neonatal autoimmune thrombocytopenia should be considered in any neonate who has early-onset thrombocytopenia and a maternal history of either immune thrombocytopenia (ITP) or an autoimmune disease (with or without thrombocytopenia). A term male baby, born to a 23-year-old primi-gravida with ITP was found to be thrombocytopenic at birth (platelets-85×10&lt;sup&gt;3&lt;/sup&gt;/µl) without any sign of neonatal sepsis. On serial monitoring, platelet counts kept falling and on day 3, the child developed severe thrombocytopenia (platelets-6.5×10&lt;sup&gt;3&lt;/sup&gt;/µl). No obvious signs of bleeding were present and the child was clinically well. Given the history of maternal thrombocytopenia (likely ITP), a possibility of neonatal autoimmune thrombocytopenia was considered. Owing to the risk of massive bleed, the baby was transfused random donor platelets and intravenous immunoglobulin (IVIg) was started on day 3. Thereafter, the platelets showed an increasing trend and child was discharged on day 7 with a platelet count of 170×10&lt;sup&gt;3&lt;/sup&gt;/µl. However, on follow-up platelet count was again found to be low (84×10&lt;sup&gt;3&lt;/sup&gt;/µl). It normalised subsequently, without any further requirement of IVIg. High index of suspicion, immediate work-up and diagnosis, with close monitoring and prompt management is required to prevent hemorrhagic complications in such children. Counselling for risk of thrombocytopenia in future pregnancies should be provided to parents.&lt;/p&gt;

Bleeding Complications Associated with Pregnancy with Primary Immune Thrombocytopenia: A Meta-Analysis

Introduction Immune thrombocytopenia (ITP) during pregnancy has received little attention from researchers. Reliable information about the outcome of mothers and newborns is required to properly counsel women who are pregnant or planning to become pregnant. Our primary outcomes were the frequency and severity of maternal and neonatal bleeding events in the setting of ITP in pregnancy. Mode of delivery, neonatal thrombocytopenia, and maternal/infant mortality were secondary outcomes. Material and Methods We comprehensively reviewed the prospective studies that enrolled ≥20 pregnant women with primary ITP. Two reviewers, blinded to each other, searched Medline and Embase up to February 2021. Meta-analyses of the maternal and newborn outcomes were performed. Weighted proportions were estimated by a random-effects model. Results From an initial screening of 163 articles, 15 were included, encompassing 1,043 pregnancies. The weighted event rate for bleeding during pregnancy was 0.181 (95% confidence interval [CI], 0.048–0.494). Most of these were nonsevere cases. The weighted event rates were 0.053 (95% CI, 0.020–0.134) for severe postpartum hemorrhage, 0.014 (95% CI, 0.008–0.025) for intracerebral hemorrhage, and 0.122 (0.095–0.157) for severe thrombocytopenia events in neonates (platelet count <50,000/μL). There were no reliable predictors of severe neonatal thrombocytopenia. The incidence of neonatal mortality was 1.06%. There were no maternal deaths. Conclusion Primary ITP in pregnant women is rarely associated with poor outcomes.

Risk factors for severe neonatal thrombocytopenia in cases of maternal immune thrombocytopenia.

Maternal immune thrombocytopenia (ITP) may induce neonatal thrombocytopenia (nTP), which carries a risk of neonatal haemorrhagic complications. Some risk factors for nTP have reached consensus such as maternal splenectomy and previous severe nTP, while others such as maternal platelet count have not. We conducted a retrospective cohort study in a university hospital, including 145 neonates of mothers with ITP. We assessed the risk of severe nTP and bleeding complications. Severe nTP in the first 24h after birth was more common in case of maternal splenectomy (OR=4.4) and a previous severe nTP (OR=46.9). Severe nTP at nadir (lowest platelet count during the initial postnatal days) was more frequent in cases of a previous neonate with severe nTP (OR=42), maternal treatment during pregnancy (OR=2.4) and a low maternal platelet count during pregnancy or at delivery. These risk factors were not significantly associated with an increased risk of neonatal haemorrhagic complications. In our population, we confirm the risk of severe nTP in case of maternal splenectomy or previous nTP. By monitoring the platelet count to its nadir, we identified three additional risk factors: maternal treatment during pregnancy and low maternal platelet count during pregnancy or low maternal platelet count at delivery.

Anaesthetic management of a parturient with severe idiopathic thrombocytopenia and neonatal thrombocytopenia posted for elective caesarean section

Anaesthetic management of a parturient with severe idiopathic thrombocytopenia and neonatal thrombocytopenia posted for elective caesarean section

Management of high-risk pregnancies in a context of maternal antiplatelet alloimmunization: Expert opinion of the French-speaking working group

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800-1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT). The objective was to survey clinical practices for management of high-risk pregnancies in a context of suspected or confirmed FNAIT. Recommendations published by the ICTMG were translated in French, and discussed (Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. British J of Haematology, 2019, 185, 549-562). The study involved centers from France, Switzerland and Belgium: Angers, Besançon, Bordeaux, Brest, Créteil/Clamart, Genève, Grenoble, Liège, Lille, Lyon, Marseille, Nantes, Nîmes, Paris (hôpitaux Necker, Robert Debré et Trousseau), Poitiers, Rennes, Saint-Etienne, Strasbourg, Toulouse, Tours. Expert opinion was validated on September 23, 2020 (consensus≥90%).

Risk Factors and Outcome of Neonatal Thrombocytopenia

Introduction: About 30% of neonates develop thrombocytopenia during hospital admission. Inevitable and irreversible complications can be prevented by determining the risk factors of neonatal thrombocytopenia. The present study was undertaken to determine the risk factors and outcome of neonatal thrombocytopenia in neonates admitted to Neonatal Intensive Care Unit Benazir Bhutto Hospital Rawalpindi.&#x0D; Materials and Methods: A prospective study was conducted to evaluate the risk factors for neonatal thrombocytopenia (NT) in 160 neonates. Neonatal and maternal risk factors were recorded and neonates were categorized into three groups based on the severity of thrombocytopenia.&#x0D; Results: A higher percentage of the neonates 89 (55.6%) were male. The majority (61.9%) had moderate neonatal thrombocytopenia while 21.9% had severe neonatal thrombocytopenia. A highly significant difference was observed for the distribution of gestational age, platelet count, birth weight, and age at admission (for all p-value ≥0.0001) among different groups. Multivariate logistic regression revealed a significant independent association of prematurity, birth asphyxia, and low birth weight with neonatal thrombocytopenia.&#x0D; Conclusion: Prematurity, low birth weight, and birth asphyxia were the significant causes of Neonatal thrombocytopenia. The mortality rate increased significantly with the severity of thrombocytopenia.

Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of HLA-DRB3*01:01 on fetal/neonatal outcome

AbstractThe most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3*01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count <50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3*01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3*01:01+ women. For HLA-DRB3*01:01− women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a− women who are HLA-DRB3*01:01−.

Neonatal alloimmune thrombocytopenia due to anti-HPA 5a in a HPA-5a homozygous neonate

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Cases of FNAIT caused by HPA-5a antigen are extremely rare, and usually not severe. We report a case of FNAIT caused by anti-HPA antibodies directed to the HPA-5a antigen. The thrombocytopenia was moderate with a minimal platelet count of 36 × 109/L by day 3, and spontaneously resolved by day 10.The pregnancy had been obtained by in vitro fertilization using embryo donation, creating a complete genetic disparity between the HPA 5b5b mother and the HPA 5a5a homozygous neonate.The use of ART with gamete donation can increase the risk and the severity of alloimmune thrombocytopenia and must be considered in new and subsequent pregnancies.

Neonatal thrombocytopenia\u2014causes and outcomes following platelet transfusions

We evaluated the causes for neonatal thrombocytopenia (NT), the duration of NT, and the indications of platelet transfusions (PT) by means of a retrospective cohort study over a 23-year period. Neonates with NT were identified via ICD-10 code D69.6. Of 371 neonates (1.8/1000 live births) with NT, the majority (312; 84.1%) had early onset thrombocytopenia, and 282 (76%) were preterm born. The most frequent causes for NT were early and late onset sepsis and asphyxia. The mean duration of thrombocytopenia was 10.2 days and was negatively correlated (KK = − 0.35) with the number of PT. PT were given to 78 (21%) neonates, 38 (49%) of whom had very severe NT. The duration of NT was positively related to the severity of NT and the number of subsequent PT. A mortality rate of 10.8% was significantly associated with bleeding signs (p < 0.05) and correlated with increasing number of PT (p < 0.05) but not with the severity of NT (p = 0.4). In the case of relevant hemorrhage, PT did not influence the mortality rate (p = 0.09). All deaths followed neonatal sepsis.Conclusions: Prematurity and diagnoses including early and late onset sepsis and asphyxia were the most common causes of NT. Mortality was not associated with the severity of NT but increased with the number of PT.What is Known:• The causes for neonatal thrombocytopenia (NT) are well known.• The effects of platelet transfusions (PT) and its indications are still a matter of debate and recommendations differ widely.What is New:• The duration of NT is positively related to the severity of NT and the number of subsequent PT.• The mortality rate is not associated with the severity of NT but increases with increasing numbers of PT and in the case of relevant intraventricular hemorrhage (≥ grade II), PT does not influence the mortality rate.

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Cab4b, the first human platelet antigen carried by glycoprotein IX discovered in a context of severe neonatal thrombocytopenia

Background After three miscarriages, a 39-year-old woman gave birth, with a 1-year interval, to two severely thrombocytopenic neonates (4 ×109 L-1 and 33 ×109 L-1 ) with intracranial hemorrhages. Transfusion of platelet concentrates corrected the thrombocytopenia. The outcome was favorable for the first child, but the second one died 10 days after cesarean delivery (31 weeks of gestation + 6 days). Methods Serologic studies were performed with mAb-specific immobilization of platelet antigens and flow cytometry techniques. Human platelet alloantigen (HPA) genotyping was performed with the BioArray HPA BeadChip and PCR-sequence-specific primer techniques. Genomic DNA was studied by direct sequencing of PCR products. The mutant glycoprotein (GP) was expressed in transiently transfected HEK293 cells. Results In MAIPA assay, the maternal serum faintly reacted with GPIbIX from paternal and child 1 platelets, but not with maternal or panel platelets. No maternofetal incompatibility was found in the 22 known HPA systems, tested except for HPA-1b in child 2. A new alloantigen carried by GPIbIX was suspected. Genomic sequencing revealed a paternal GPIX variation (NM_000174.4:c.368C>T). The father and children were heterozygous and incompatible with the mother, who was NM_000174.4:c.368C homozygous. The maternal serum reacted with the GPIX NP_000165.1:p.Leu123 form coexpressed with GPIb in transfected HEK293 cells. The NM_000174.4:c.368T allele (rs202229101) has a minor allele frequency of 0.0002, and was not detected in 120 French subjects (families with fetal and neonatal alloimmune thrombocytopenia [FNAIT]), suggesting that it is rarely implicated in alloimmunization. Conclusion The NP_000165.1:p.Leu123 allele named Cab4b is the first platelet alloantigen described on GPIX. In the absence of other known maternofetal incompatibility, the child 1 case suggests that anti-Cab4b alloantibodies can induce severe thrombocytopenias.

Imaging and management of fetuses and neonates with alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of severe neonatal thrombocytopenia and intracranial bleeding in term newborns. Intracranial hemorrhage (ICH) commonly results in death or severe, lasting neurologic disability. The timing of ICH is also important for management of the next affected pregnancy in cases of FNAIT. This manuscript reviews the advantages and disadvantages of the different radiologic methodologies to identify and characterize ICH. It discusses the limits of ultrasound and the advantages of magnetic resonance imaging allowing avoidance of the radiation associated with computed tomography (CT) scans.

Severe neonatal alloimmune thrombocytopenia caused by maternal sensitization against a new low-frequency alloantigen (Domb ) located on platelet glycoprotein IIIa.

Severe neonatal alloimmune thrombocytopenia caused by maternal sensitization against a new low-frequency alloantigen (Domb ) located on platelet glycoprotein IIIa.

Fetal and neonatal alloimmune thrombocytopenia - pathogenesis, diagnosis and therapy

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) represents the most frequent cause of severe fetal or neonatal severe thrombocytopenia and intracranial haemorrhage in full-term infants. It should be suspected with isolated thrombocytopenia or with a personal or family history of alloimmune thrombocytopenia, especially if the fetus experienced intracranial haemorrhage. FNAIT results from maternal alloimmunization during pregnancy against specific fetal platelet antigens (HPA) inherited from the father and absent in the mother. These maternal IgG alloantibodies bind to the fetal platelets, leadind to their distruction. Although rare, FNAIT has a poor outcome, due to possible severe complications and long-term disabilities. The immediate antenatal maternal treatment, using high dose i.v. IG and corticosteroids has shown that both the degree of thrombocytopenia in the fetus and the risk of intracranial haemorrhage can be reduced. The aim of this paper is to put an exclamation point on the importance of adequate diagnosis and treatment on reducing both associated morbidity and mortality. We worked on a meta-analysis of numerous studies, drawing conclusions on pathogenesis, genetic testing, diagnosis and screening principles, as well as on treatment recommendations based on antenatal risk stratification algorithms. We present in detail the severity-based approach for treatment of pregnancies at undetermined risk, standard, high and extremely high risk, so this paper could be even used as a guide to FNAIT management. An important chapter is the management of subsequent pregnancies, where we presented the latest protocols of recommendation for parental and fetal genotyping and methods for estimating the severity of FNAIT.

Fatal alloimmune thrombocytopenia due to anti-HLA alloimmunization in a twin pregnancy: A very infrequent complication of assisted reproduction

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Platelets express the HLA-A and B antigens on their membrane and some studies report that maternal anti-HLA class I antibody can also cause FNAIT. We report here a very unusual case of a first twin pregnancy produced in vitro by oocyte and semen donation where the mother developed markedly elevated HLA antibodies, in the absence of anti-platelet or anti-neutrophil antibodies, that provoked in one of the twins a profound thrombocytopenia and intracranial hemorrhage and a mild thrombocytopenia and neutropenia in the second twin lasting until the fourth month of life. In addition, anti-D alloimmunization provoked hemolytic disease of the newborn with intrauterus anemia detected in the first twin and post-natal anemia in the second twin that required red blood cell transfusion and phototherapy. We hypothesize that the complete HLA-incompatible twin pregnancy due to the oocyte donation might have contributed to the severity of the clinical manifestations.

Severe neonatal thrombocytopenia in a case of Cornelia de Lange syndrome

Patients of Cornelia de Lange syndrome (CdLS) may be more susceptible for the development of immune thrombocytopenia than the general population, for which many hypotheses have been generated. However, till date, only a few cases of thrombocytopenia in CdLS have been described; only four reports being from neonates. Here, we describe a case of severe, symptomatic and idiopathic neonatal thrombocytopenia in CdLS from India, which remitted spontaneously without any serious sequel. Diagnostic clinical criteria of CdLS are also discussed.

Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome

Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

How do we treat fetal and neonatal alloimmune thrombocytopenia?

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in one in 800 to 1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. The complication of this disorder most to be feared is intracranial hemorrhage, leading to death or to neurologic sequels. As there is no systematic screening of at-risk pregnancies, FNAIT is often discovered when signs of bleeding are observed during pregnancy or at delivery. Platelet transfusion is required in case of bleeding or severe thrombocytopenia (<30 × 10(9) /L) during the 48-hour-postdelivery period. Diagnosis of alloimmunization is important for management of the index case and for subsequent pregnancies, due to the increasing severity of this syndrome as it recurs. Noninvasive antenatal therapy is based on maternal perfusion of intravenous immunoglobulins and risk stratification. In our experience, the addition of corticoids during the last trimester significantly improves the efficiency of treatment. Follow-up of antibody concentration during pregnancy may constitute a useful variable for therapy effectiveness.