Choosing Between Strategies for Managing Fetal or Neonatal Alloimmune Thrombocytopenia

For women diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT), a noninvasive strategy of weekly intravenous immunoglobulin infusion (IVIg) and corticosteroids could help prevent the development of FNAIT in subsequent pregnancies, according to the results of a systematic review published in Blood. More invasive strategies, such as serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPTs), resulted in higher complication rates than noninvasive techniques.

FNAIT can lead to severe bleeding complications in the fetus and newborn babies, and as a result of the lack of population-based screening programs, it is typically identified only after an incidental finding of neonatal thrombocytopenia, wrote the authors, led by Dian Winkelhorst, from the Department of Obstetrics at the Leiden University Medical Center in The Netherlands.

“No international consensus on the optimal antenatal management of FNAIT exists, and numerous strategies – non-invasive as well as invasive – are applied in different centers that specialize in antenatal therapy,” the authors explained.

The researchers searched Medline, EMBASE, and the Cochrane Library for English-language studies published between 1946 and December 2015 that met the following criteria:

  • included ≥5 pregnant women with pregnancies at risk for FNAIT or fetuses/neonates diagnosed with FNAIT
  • included patients treated with either IVIg, steroids, or IUPT
  • included outcomes of intracranial hemorrhage (ICH) and fetal/neonatal platelet count

The final cohort consisted of 26 studies: four randomized, controlled trials; five prospective studies; and 17 retrospective studies. The studies investigated the following antenatal FNAIT management strategies:

  • IVIg alone (n=17 studies)
  • corticosteroids alone (n=3)
  • IVIg and corticosteroids (n=11)
  • FBS (n=24)
  • FBS with IUPT (n=16)
  • IUPT alone (n=5)
  • IUPT and IVIg (n=3)

Though pooling of results was not possible due to the “considerable heterogeneity” of the study sample, the authors reported that “most studies found comparable outcomes regarding the occurrence of ICH, regardless of antenatal management strategy applied (FBS, IUPT, or IVIg with or without corticosteroids).”

All but one study included information on ICH. In a total of 839 pregnancies, 24 ICHs were observed (3%); seven occurred before treatment started, and one developed in a patient who received no treatment. IVIg had a 98.7 percent success rate in preventing ICH (4 ICHs in 315 pregnancies).

Twenty-four studies (totaling 821 pregnancies) assessed mortality, reporting an overall mortality rate of 4 percent (30 deaths). Seventeen deaths were related to FBS/IUPT treatment (53%), and seven were due to ICH (22%).

There was no consistent evidence for the value of adding steroids to IVIg, and the rate of treatment-related complications appeared to be higher when IVIg was used with corticosteroids (values not reported). The most commonly reported side effect of corticosteroid treatment was oligohydramnios; the most commonly reported side effects of IVIg were headache and rash, which led to IVIg discontinuation in one patient.

Comparatively, of the 24 studies in which patients were treated with FBS with or without IUPT, the rate of complications was relatively high (11%, or 54 complications in 497 treated pregnancies). The most frequently described complications were emergency cesarean section, mostly due to fetal distress; approximately half of these procedures resulted in delivery prior to 34 weeks’ gestation. Fourteen complications resulted in fetal or neonatal death (26%).
“Regarding the optimal dose and start of the treatment, there are insufficient data to recommend a specific gestational age or specific dose,” Dr. Winkelhorst and co-authors wrote. However, the data supported the following treatment strategies:

  • treatment of high-risk pregnancies (i.e., sibling suffered from ICH): IVIg 1 g/kg per week, started between 12 and 20 weeks’ gestation
  • treatment of standard-risk pregnancies (i.e., no sibling suffered from ICH): IVIg 1 g/kg per week with or without steroids, started between 20 and 24 weeks’ gestation

The authors cautioned that the use of IVIg in pregnancies at risk for FNAIT is “still off-label and the possible immunostimulative or immunosuppressive effect of exposing the maturing fetal immune system to IVIg has not been adequately addressed.” They added that the study was limited by the small number of randomized studies and lack of an adequate control group, as well as the heterogeneity of extracted data.


Reference

Winkelhorst D, Murphy MF, Greinacher A, et al. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review. Blood. 2017 January 11. [Epub ahead of print]

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