Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia. Antepartum treatment without early cordocentesis for standard-risk alloimmune thrombocytopenia: a randomized controlled trial. Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin.
Antenatal therapy with intravenous immunoglobulin (IVIG) and prednisone has been shown to improve fetal thrombocytopenia and reduce the incidence of intracranial hemorrhage in neonatal alloimmune thrombocytopenia. Optimization of this therapy for individual patients, however, has yet to be achieved.
                In these parallel, randomized, multicenter studies, 78 patients in 79 pregnancies were stratified to 2 different treatment arms based on the presence of a peripartum intracranial hemorrhage in a previously affected sibling and/or the initial fetal platelet count. Patients with a history of an antenatal intracranial hemorrhage in a prior pregnancy were excluded.
                Forty women whose children from a previous birth had a peripartum intracranial hemorrhage or whose current fetus had an initial platelet count less than 20,000/mL3 were randomly assigned to receive IVIG plus prednisone or IVIG alone. The mean increase in fetal platelet counts in the following 3 to 8 weeks was 67,100/mL3 and 17,300/mL3, respectively (P < .001). Thirty-nine patients whose prior affected child did not have an intracranial hemorrhage and whose initial platelet count was more than 20,000/mL3 were randomly assigned to receive IVIG alone or prednisone alone. There were no significant differences, and 33 (85%) had birth platelet counts more than 50,000/mL3. There were 11 (6%) significant complications after a total of 175 fetal blood sampling procedures, 2 of which led to fetal or neonatal deaths.
                The spectrum of disease severity of alloimmune thrombocytopenia is reflected in the initial fetal platelet count and response to therapy. Fetal blood sampling may be associated with significant fetal/neonatal morbidity and mortality. Empiric therapy sufficient to treat the most severely affected fetuses will overtreat others and is likely to be associated with additional maternal morbidity. To evaluate the effectiveness and safety of two antenatal treatment regimens designed to optimally protect fetuses against intracranial hemorrhage resulting from alloimmune thrombocytopenia while minimizing the risks associated with fetal blood sampling. The study was limited to "standard-risk" patients, who were defined as women with documented alloimmune thrombocytopenia who had not delivered an infant with an intracranial hemorrhage in a prior pregnancy.
                In this prospective multicenter study of 73 women with documented alloimmune thrombocytopenia, patients were randomized to receive either intravenous immunoglobulin (IVIG) 2 g/kg/wk (group A) or IVIG 1 g/kg/wk plus prednisone 0.5 mg/kg/d (group B), starting at approximately 20 weeks of gestation. Fetal blood sampling was performed at approximately 32 weeks of gestation, and those with fetal platelet counts less than 30,000/mL(3) were given salvage therapy.
                There were two intracranial hemorrhages; neither was due to treatment failure. The average platelet counts at the time of fetal blood sampling were 121,600/mL(3) and 116,100/mL(3), and the average birth platelet counts were 169,400/mL(3) and 134,000/mL(3) for groups A and B, respectively. Twenty-seven percent of patients in group A and 17% in group B received salvage therapy, and only one neonate in each of these subsets had a birth platelet count less than 30,000/mL(3). There were four complications after 79 fetal blood sampling procedures, leading to cesarean deliveries between 32 and 37 weeks. There was a higher incidence of gestational diabetes and a tendency to more fluid retention, mood swings, insomnia, and jitteriness in patients on prednisone and of moderate-to-severe fatigue in those on high-dose IVIG alone.
                The outcomes of both treatment groups were excellent and comparable. Early cordocentesis is not necessary when treating alloimmune thrombocytopenia in patients who have not delivered an infant with an intracranial hemorrhage in a prior pregnancy.
                ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194987
                I. Our purposes were to investigate maternal infusions of intravenous gamma-globulin, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous gamma-globulin.
                Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous gamma-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous gamma-globulin plus 60 mg of prednisone per day ("salvage").
                Dexamethasone did not add to the effect of intravenous gamma-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/microliters (n = 47) and from the first fetal blood sampling to birth of 69,000/microliters (n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. "Salvage" increased the platelet count in 5 of 10 nonresponders to intravenous gamma-globulin.
                Intravenous gamma-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia.
The optimal management of fetomaternal alloimmune thrombocytopenia remains unclear. Lack of complete data sets for two trials and differences in interventions precluded the pooling of data from these trials which may have enabled a more developed analysis of the trial findings. Further trials would be required to determine optimal treatment (the specific medication and its dose and schedule). Such studies should include long-term follow up of all children and mothers.