Neonatal Biomarkers of Inflammation: Correlates of Early Neurodevelopment and Gait in Very-Low-Birth-Weight Preterm Children

Objective Neonatal biomarkers of inflammation were examined in relation to early neurodevelopment and gait in very-low-birth-weight (VLBW) preterm children. We hypothesized that preterm infants exposed to higher levels of neonatal inflammation would demonstrate lower scores on Bayley Scales of Infant Toddler Development, 3rd ed. (BSID-III) and slower gait velocity at 18 to 22 months adjusted age. Study Design A total of 102 VLBW preterm infants (birthweight [BW] <= 1,500 g, gestational age [GA] <= 32 weeks) admitted to neonatal intensive care unit [NICU] were recruited. Neonatal risk factors examined were GA at birth, BW, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and serum C-reactive protein (CRP), albumin, and total bilirubin over first 2 postnatal weeks. At 18 to 22 months, neurodevelopment was assessed with BSID-III and gait was assessed with an instrumented mat. Results Children with neonatal CRP >= 0.20 mg/dL (n = 52) versus < 0.20 mg/dL (n = 37) had significantly lower BSID-III composite cognitive (92.0 +/- 13.1 vs. 100.1 +/- 9.6, p = 0.002), language (83.9 +/- 16.0 vs. 95.8 +/- 14.2, p < 0.001), and motor scores (90.0 +/- 13.2 vs. 98.8 +/- 10.1, p = 0.002), and slower gait velocity (84.9 +/- 19.0 vs. 98.0 +/- 22.4 cm/s, p = 0.004). Higher neonatal CRP correlated with lower cognitive (rho = - 0.327, p = 0.002), language (rho = - 0.285, p = 0.007), and motor scores (rho = - 0.257, p = 0.015), and slower gait (rho = - 0.298, p = 0.008). Multivariate analysis demonstrated neonatal CRP >= 0.20 mg/dL significantly predicted BSID-III cognitive (adjusted R-2 = 0.104, p = 0.008), language (adjusted R-2 = 0.124, p = 0.001), and motor scores (adjusted R-2 = 0.122, p = 0.004). Conclusions Associations between low-level neonatal inflammation and neurodevelopment suggest early biomarkers that may inform neuroprotective treatment for preterm children.