Long-term outcome of brain structure in premature infants: effects of liberal vs restricted red blood cell transfusions

Abstract

Objective: To assess the long-term outcome of brain structure in preterm infants, at an average age of 12 years, who received a red blood cell transfusion for anemia of prematurity.

Design: As neonates, this cohort of infants participated in a clinical trial in which they received red blood cell transfusions based on a high pretransfusion hematocrit threshold (liberal group) or a low hematocrit threshold (restricted group). These 2 preterm groups were compared with a group of full-term healthy control children.

Setting: Tertiary care hospital.

Participants: Magnetic resonance imaging scans for 44 of the original 100 subjects were obtained.

Intervention: Liberal vs restricted transfusion.

Main outcome measures: Intracranial volume, total brain tissue, total cerebrospinal fluid, cerebral cortex and cerebral white matter volume, subcortical nuclei volume, and cerebellum volume.

Results: Intracranial volume was substantially smaller in the liberal group compared with controls. Intracranial volume in the restricted group was not different from controls. Whole-cortex volume was not different in either preterm group compared with controls. Cerebral white matter was substantially reduced in both preterm groups, more so for the liberal group. The subcortical nuclei were substantially decreased in volume, equally so for both preterm groups compared with controls. When sex effects were evaluated, the girls in the liberal group had the most significant abnormalities.

Conclusion: Red blood cell transfusions affected the long-term outcome of premature infants as indicated by reduced brain volumes at 12 years of age for neonates who received transfusions using liberal guidelines.

Trial registration: ClinicalTrials.gov NCT00369005.

Figures

Figure 1

The z scores of all brain measures. The 2 preterm groups (liberal girls in gray and liberal boys in black) were compared against their respective sex-matched control group. The control group represents the midline 0 on the y-axis, and therefore, negative scores on the y-axis indicate volumes that are lower than the controls and positive scores on the y-axis indicate volumes that are higher than the controls. *Measures that are significantly different than controls. CSF indicates cerebrospinal fluid, ICV, intracranial volume.

Figure 2

The z scores of cortical gray matter regions. The 2 preterm groups (liberal girls in gray and liberal boys in black) were compared against their respective sex-matched control group. The control group represents the midline 0 on the y-axis, and therefore, negative scores on the y-axis indicate volumes that are lower than the controls and positive scores on the y-axis indicate volumes that are higher than the controls. *Measures that are significantly different than controls.

Figure 3

The z scores of white matter regions. The 2 preterm groups (liberal girls in gray and liberal boys in black) were compared against their respective sex-matched control group. The control group represents the midline 0 on the y-axis, and therefore, negative scores on the y-axis indicate volumes that are lower than the controls and positive scores on the y-axis indicate volumes that are higher than the controls. *Measures that are significantly different than controls.