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A new observation - chronic villitis in untreated neonatal alloimmune thrombocytopenia (NAIT): An etiology for severe early intrauterine growth restriction (IUGR) and the effect of intravenous immunoglobulin (IVIG) therapy

      Objective

      To examine placental histopathology in IVIG-treated and untreated NAIT pregnancies and correlate pathological findings with clinical outcomes.

      Study design

      Placentas of 14 NAIT-affected pregnancies were identified from 8 women. Data concerning maternal antepartum treatment with IVIG (1 g/kg weekly) vs no treatment, and fetal/neonatal outcomes including IUGR, intrauterine fetal demise (IUFD), and intracranial hemorrhage (ICH) were abstracted from the medical records. Placental H&E sections were read and graded (mild, moderate, severe) by two pathologists blinded to the clinical data. Histopathology and clinical outcomes were compared between IVIG and no IVIG treatment groups using χ2. One subject, not treated until after an ICH was diagnosed at 21 weeks, was excluded from the analysis. P < .05 was considered significant.

      Results

      Five of 6 untreated pregnancies demonstrated pathological changes in the placenta including chronic villitis, advanced villus maturation, and increased syncytial knots (Table). IUGR and IUFD occurred as frequently as ICH in this group, with one subject presenting with her 3rd pregnancy affected by severe early IUGR. Seven pregnancies were treated with IVIG beginning at 12 ( n = 6) or 17 (n = 1) weeks. None of the 7 IVIG-treated pregnancies showed chronic villitis or any histologic findings described as severe. IUGR, IUFD or ICH did not occur in the IVIG-treated group.

      Conclusion

      Chronic villitis is frequently manifest in NAIT, with IVIG alleviating this inflammatory immunologic response. NAIT should be reconsidered as a multifaceted disease process with adverse consequences that extend beyond thrombocytopenia and include IUGR and IUFD. We suspect a more universal role for the maternal antibody in NAIT, such as fetal endothelial cell damage.
      Tabled 1Outcomes by IVIG status
      − IVIG+ IVIGP value
      Chronic villitis5 (83.3%)0.005
      Other histopath5 (83.3%)3 (42.9%).266
      ICH1 (16.7%)0.46
      IUGR2 (33.3%)0.56
      IUFD3 (50%)0.07