Clinical and laboratory predictors of fetal and neonatal alloimmune thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of intracranial hemorrhage (ICH) in thrombocytopenic term infants. We investigated clinical and laboratory predictors of severe FNAIT in a tertiary care referral center.

Retrospective cohort study over a 30-year period. We defined FNAIT as recurrence of neonatal thrombocytopenia in a subsequent pregnancy; and severe outcomes as any of: (1) a birth platelet count below 20 × 10⁹ /L; (2) ICH or (3) fetal death. We used a generalized estimating equations analysis and classification tree analysis to identify risk factors for severe FNAIT in a subsequent pregnancy.

During index pregnancies (n = 135 in 131 mothers), 71 infants (52.6%) had severe outcomes including a platelet count <20 × 10⁹ /L (n = 45), fetal or neonatal ICH (n = 32), or fetal death (n = 4). During subsequent pregnancies (n = 72), 15 infants (20.8%) had severe outcomes including birth platelets <20 × 10⁹ /L (n = 10), ICH (n = 2), or death (n = 3). Forty-two women (58.3%) received antenatal intravenous immune globulin (IVIG) during subsequent pregnancies. Eight mothers (n = 9 infants) had severe FNAIT outcomes despite receiving antenatal IVIG. Maternal antibodies to human platelet antigens (HPA) was the only independent predictor of severe FNAIT in a subsequent pregnancy (OR = 25.3, p = .004). Nevertheless, one of 43 infants from antibody-negative mothers had a severe outcome.

The presence of anti-HPA is highly indicative of the diagnosis of severe FNAIT; however, we observed one infant who had severe FNAIT recurrence, defined using strict clinical criteria, without a maternal antibody. Improved diagnostic and therapeutic strategies are needed to prevent severe FNAIT in high-risk mothers.