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

Abstract

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 R² = 0.104, p = 0.008), language (adjusted R² = 0.124, p = 0.001), and motor scores (adjusted R² = 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.

Keywords

preterm infants - neonatal risk factors - biomarkers of inflammation - neurodevelopment - gait

Funding

This research was supported by the National Institute of Health Clinical and Translational Science Award UL1 RR025744 for the Stanford Center for Clinical and Translational Education and Research (Spectrum) and for the Stanford Center for Clinical Informatics and Stanford Translational Research Integrated Database Environment (STRIDE), and by the Lucile Packard Foundation for Children's Health. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under grant no. DGE-1147470 and was supported by the Chiesi Foundation, Parma, Italy and by the Mary Baracchi Research Fund, Lucile Packard Children's Hospital, Stanford. The authors have stated that they had no interests that might be perceived as posing a conflict or bias and there was no involvement of funders in study design, data collections, data analysis, article preparation, and/or publication decisions.

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