Anemia of prematurity and cerebral near-infrared spectroscopy: should transfusion thresholds in preterm infants be revised?

Abstract

Objective: To determine the impact of progressive anemia of prematurity on cerebral regional saturation (C-rSO₂) in preterm infants and identify the hemoglobin threshold below which a critical decrease (>2SD below the mean) in C-rSO₂ occurs.

Study design: In a cohort of infants born ≤30 weeks EGA, weekly C-rSO₂ data were prospectively collected from the second week of life through 36 weeks post-menstrual age (PMA). Clinically obtained hemoglobin values were noted at the time of recording. Recordings were excluded if they were of insufficient duration (<1 h) or if the hemoglobin was not measured within 7 days. Statistical analysis was performed using a linear mixed effects-model and ROC analysis. ROC analysis was used to determine the threshold of anemia, where C-rSO₂ critically decreased >2SD below the mean normative value (<55%) in preterm infants.

Results: In total 253 recordings from 68 infants (mean EGA 26.9 ± 2.1 weeks, BW 1025 ± 287 g, 49% male) were included. Approximately 29 out of 68 infants (43%) were transfused during hospitalization. Mixed-model statistical analysis adjusting for EGA, BW, and PMA revealed a significant association between decreasing hemoglobin and C-rSO₂ (p < 0.01) in transfusion-naive infants but not in transfused infants. In the transfusion naive group, using ROC analysis demonstrated a threshold hemoglobin of 9.5 g/dL (AUC 0.81, p < 0.01) for critical cerebral desaturation in preterm infants.

Conclusions: In transfusion-naive preterm infants, worsening anemia was associated with a progressive decrease in cerebral saturations. Analysis identified a threshold hemoglobin of 9.5 g/dL below which C-rSO₂ dropped >2SD below the mean.

Figure 1

A graphical illustration of the rolling average computation used to empirically derive the 1 hour (3,600 sample) minimum for recording length. Stabilization of the mean C-rSO₂ value of the above 7 hour (25,000 sample) recording occurs within the first hour (indicated by the dashed line). This was a consistent finding, demonstrating that 1 hour of data is sufficient to compute a mean C-rSO₂ value that is reflective of that of a 6–8 hour recording.

Figure 2

Scatter plots illustrating the correlation between hemoglobin and C-rSO₂ in transfused (left) and non-transfused infants. Both groups exhibit statistically-significant positive correlations indicating that C-rSO₂ decreases with worsening anemia. The correlation is weak in the transfused group (r²=0.04, p=0.02) and moderate in the non-transfused group (r²=0.24, p<0.01).

Figure 3

ROC curves for all infants (left), transfused infants (middle), and non-transfused infants (right). ROC analysis was significant for all infants and the non-transfused group, but not for the transfused group (AUC 0.57, p=0.17). For all infants, there was marginal discrimination (AUC 0.70, p<0.01). For the non-transfused group, there was good discrimination (AUC 0.81, p<0.01).

Figure 4

The graph on the left displays the Youden’s J statistic for each hemoglobin level in the non-transfused infants. The arrow indicates the point associated with the hemoglobin threshold of 9.5g/dL. The table on the right displays the sensitivity, specificity, and Youden’s J statistic for each hemoglobin value with the chosen threshold, which maximizes sensitivity and Youden’s J, highlighted in gray.