Intracranial hemorrhages in neonates born from 32 weeks of gestation-low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study

Transfusion. 2018 Jan;58(1):223-231. doi: 10.1111/trf.14394. Epub 2017 Nov 8.


Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH.

Study design and methods: The Swedish Neonatal Quality (SNQ) register was used to identify neonates diagnosed with an ICH born between 2003 and 2012. Mothers were invited to donate peripheral blood, to investigate their HPA-1a antigen status, and test for anti-HPA and anti-HLA Class I alloantibodies. Clinical data for the neonates were retrieved from the SNQ register and available clinical records.

Results: Of 286 registered neonates, 278 mothers were contacted. Of 105 analyzed maternal samples, two (1.9%) were HPA-1a antigen negative. Antibody analyses revealed in total three (2.9%) mothers with anti-HPA: one mother (0.94%) with anti-HPA-1a and two mothers (1.9%) with anti-HPA-5b, of whom one had concurrent anti-HPA-15a. Twenty-four percent tested positive for anti-HLA Class I antibodies. A total of 8.5% of neonates (5/59) with PLT counts available in clinical records were severely thrombocytopenic, with PLT counts of less than 50 × 109 /L.

Conclusions: This retrospective cohort revealed a wide range of factors associated with ICH in neonates born from 32 weeks of gestation and suggests PLT alloimmunization to be a less common contributor than anticipated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Human Platelet / immunology
  • Female
  • Fetal Diseases / epidemiology*
  • Fetal Diseases / immunology
  • Gestational Age
  • Hemorrhage / epidemiology
  • Hemorrhage / etiology
  • Humans
  • Immunity, Maternally-Acquired
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / epidemiology*
  • Infant, Premature, Diseases / etiology
  • Integrin beta3
  • Intracranial Hemorrhages / epidemiology*
  • Intracranial Hemorrhages / etiology
  • Male
  • Platelet Count
  • Pregnancy
  • Registries
  • Retrospective Studies
  • Sweden / epidemiology
  • Thrombocytopenia, Neonatal Alloimmune / blood
  • Thrombocytopenia, Neonatal Alloimmune / epidemiology*


  • Antigens, Human Platelet
  • ITGB3 protein, human
  • Integrin beta3