Evaluation of altitude-appropriate reference ranges for neutrophils in diagnosis of sepsis in very low birth weight infants: A multicenter retrospective study

The circulating neutrophil count was commonly believed to be influenced by altitude. At present, neutrophil reference ranges (RRs) for very low birth weight (VLBW) neonates are only available from the sea level and from high altitude. This study aimed to construct RRs for neutrophils in VLBW infants in an intermediate-altitude area and assess its usefulness in evaluation for sepsis. This was a multicenter retrospective study of 2173 VLBW infants admitted to 20 hospitals in Chongqing in southwest of China with altitude from 1000 to 2600 feet. The RRs for absolute total neutrophils (ATN), absolute total immature neutrophils (ATI), and immature: total neutrophil proportion were constructed based on "normal" neonates (unlikely infection). Values of neutrophil from septic and uninfected neonates were respectively assessed using the revised RRs and the previous Mouzinho's and Schmutz's RRs. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared using the McNemar's test or χ2 test. The upper limits for ATN and ATI using the revised RRs were much higher than those using Mouzinho's RRs, but lower than those using Schmutz's RRs. The revised RRs and Mouzinho's RRs had higher sensitivities than Schmutz's RRs at 73-672 h. The revised RRs had a higher specificity than Mouzinho's RRs at both 0-72 h and 73-672 h. The NPV for any abnormality in neutrophil values was high at both 0-72 h and 73-672 h irrespective of the RRs used. Altitude-appropriate RRs for neutrophils is more suitable to guide the diagnosis and management of neonatal sepsis in VLBW infants.