Platelet Transfusion in Extremely Preterm Infants May Increase Risk of Death and Neurodevelopmental Impairment

Platelet transfusion for very preterm infants appears to be associated with a greater risk of mortality and severe neurodevelopment at 2 years, according to a trial of more than 800 infants published last week in JAMA.

Death or severe neurodevelopmental impairment (NDI) at 2 years corrected age occurred in 46.5% of infants who received a platelet transfusion in the NICU compared with 13.9% of those who did not receive transfusion. Findings were similar for death and severe NDI separately.

The study provides more data on the common use of prophylactic platelet transfusion to prevent bleeding in preterm infants with thrombocytopenia (platelet count less than 150 × 10³/microliter). Thrombocytopenia occurs between 22% to 35% of NICU patients.

Several studies have shown no correlation between platelet count and bleeding severity in these infants, suggesting that other factors likely play a more important role in the risk of bleeding. In addition, data from other recent studies have suggested that higher platelet thresholds are associated with worse outcomes

The placebo-controlled randomized PENUT trial included 819 infants born at 24 to 27 weeks gestational age (extremely preterm). Of these, 245 (30%) received at least one platelet transfusion during their initial hospitalization.

NDI was measured at 2 years corrected age (22 to 26 months) using the standardized Bayley Scales of Infant Development–Third Edition (BSID-III) to assess cognitive, motor and language development and Gross Motor Function Classification System (GMFCS) to evaluate for cerebral palsy. Severe NDI was defined as either the presence of severe cerebral palsy (GMFCS score greater than 2) or a BSID-III composite motor score or composite cognitive score two standard deviations (SD) below the mean.

Of the infants who received one or more platelet transfusions, 32.2% died before 2 years corrected age compared with 5.9% of those who did not receive a transfusion. Likewise, more infants who received one or more platelet transfusions had severe NDI compared with those who did not receive any transfusion — 21.9% versus 8.8%.

Secondary outcomes included mortality and expanded the range of NDI to include moderate to severe, where moderate NDI was defined as a GMFCS level of 2, or a BSID-III composite motor or cognitive score one SD below the mean and the individual BSID-III cognitive, motor and language scores.

Based on these expanded criteria composite outcome, death or moderate to severe NDI occurred in 68% of patients who received at least one platelet transfusion and 36% of those who did not receive any transfusion. Looking at NDI alone, moderate to severe NDI was assessed in 54% of patients who received one or more platelet transfusions and 33% of those who did not receive any transfusion.

The researchers also looked at scores for individual components of the BSID-II (motor, cognitive and language). They found that each additional platelet transfusion was associated with a 1.1-point decrease in mean motor score, though no effect on cognitive or language scores was detected.

The researchers noted that “the mechanisms underlying the possible association remain unclear and further research is needed to elucidate them. While we await these answers, evidence-based platelet transfusion practices need to be implemented in this vulnerable population to reduce unnecessary platelet transfusions that might contribute to preventable harm.”