Beyond Single Cutoffs: Gestational and Postnatal Age-Specific Interpretation of Neonatal Laboratory Markers

Interpretation of laboratory biomarkers is fundamental to neonatal clinical practice and research; however, many biomarkers continue to be applied using single universal cutoff values that insufficiently account for developmental immaturity. In newborns, serum biomarker concentrations are strongly influenced by gestational and postnatal age, reflecting dynamic developmental and inflammatory processes. This review highlights the importance of gestational and postnatal age-based interpretation of neonatal serum biomarkers, using albumin, immunoglobulin G (IgG), and interleukin-6 (IL-6) as representative examples. Albumin concentrations at birth correlate more closely with gestational age than with birth weight, likely reflecting maturation of fetal hepatic synthetic capacity, whereas postnatal albumin levels increase with fluid redistribution, nutritional status, and physiological adaptation, leading to wide variability that limits the utility of fixed thresholds. Similarly, IgG concentrations at birth are primarily determined by gestational age-dependent placental transfer and remain low for prolonged periods in preterm infants, complicating assessment of immune vulnerability and immunoglobulin supplementation. IL-6 is a sensitive indicator of inflammatory activity; however, gestational age influences the magnitude of IL-6 responses to fetal inflammation, particularly in extremely preterm infants. Together, these examples illustrate that neonatal serum biomarkers reflect dynamic developmental and inflammatory processes rather than static disease states. Interpreting laboratory values within a framework integrating gestational and postnatal age enables more biologically meaningful characterization of neonatal physiological and pathological states and supports mechanism-oriented research in neonatal medicine.