Reference ranges for lymphocyte counts of neonates: associations between abnormal counts and outcomes

Both high and low lymphocyte counts at birth have been associated with adverse outcomes. However, the validity of defining a lymphocyte count as "abnormal" depends on having an accurate reference range. We established a reference range for neonatal lymphocyte counts by using multihospital data and used this to assess previously reported relationships between abnormal counts and early onset sepsis (EOS), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), periventricular leukomalacia, and birth asphyxia. We first created a data set that excluded counts from neonates with diagnoses previously associated with abnormal lymphocyte counts. Then the complete data (counts excluded plus included in the reference range) were used to test associations between abnormal counts and EOS, IVH, ROP, periventricular leukomalacia, and outcomes after birth asphyxia. Lymphocyte counts were retrieved from 40 487 neonates, 10 860 of which were excluded from the reference range. A count >95th percentile was associated with EOS (2.07; 95% confidence interval [CI]: 1.80-2.38) and IVH ≥grade 3 (2.93; 95% CI: 1.83-4.71). A count