Will it ever be possible to balance the risk of intracranial haemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it?

Background and Objectives Intracranial haemorrhage (ICH) of the fetus or newborn is a severe complication of fetal or neonatal alloimmune thrombocytopenia (FNAIT). In order to attain management decisions to prevent ICH, the risk of ICH in successive pregnancies with thrombocytopenia, with or without a history of ICH, must be established. Materials and Methods We performed a search of medline for ICH cases in untreated FNAIT pregnancies. After exclusion of cases with confounding factors, 24 reports, describing 62 pregnancies of 27 mothers, were eligible. In addition, two mothers with five pregnancies were included from our own case records. Observational studies were examined to estimate the risk of ICH in subsequent FNAIT pregnancies without a history of ICH. Finally, medline was searched for complication rates in the treatment of FNAIT pregnancies. Results In 52% of the ICH cases, a previous sibling suffered from ICH. The recurrence rate of ICH in the subsequent offspring of women with a history of FNAIT with ICH was 72%[confidence interval (CI): 46-98%] without inclusion of fetal deaths and 79% (CI: 61-97%) with inclusion of fetal deaths. In 48% of the ICH cases, the previous sibling had thrombocytopenia but not ICH. Population studies revealed an overall ICH risk in thrombocytopenic infants of 11% (CI: 0.8-23%) without inclusion of fetal deaths and 15% (CI: 1.5-19%) with inclusion of fetal deaths. Assuming occurrence in 48%, the risk of ICH in a subsequent pregnancy following a history of FNAIT without ICH, was estimated to be 7% (CI: 0.5-13%). Invasive treatment strategies carry a risk of 2.8% (CI: 1.2-4.4%) on complications. Conclusions The number of eligible publications on ICH in untreated FNAIT pregnancies is strikingly limited. The recurrence rate is high. As sufficient data on successive FNAIT cases without ICH are lacking, the occurrence of ICH in pregnancies with thrombocytopenia, but without ICH in a previous sibling, cannot be predicted. We estimate this risk to be 7%. This risk must be balanced against the risk of interventions in treatment strategies.