title: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rose
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Rachel
authors.initials: R
authors.lastname: Vassar
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Cahill-Rowley
authors.affiliation: Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Hintz
authors.affiliation: Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001724:Birth Weight; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology; D002097:C-Reactive Protein / Q000032:analysis; D002657:Child Development; D003071:Cognition; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology; D005260:Female; D005684:Gait; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D019102:Infant, Very Low Birth Weight / Q000254:growth & development*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis*; D007363:Intensive Care Units, Neonatal; D016014:Linear Models; D008297:Male; D009043:Motor Activity; D015999:Multivariate Analysis; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D018805:Sepsis / Q000453:epidemiology; D013060:Speech
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein