Neonatal creatinemia trends as biomarker of subsequent cognitive outcome in extremely low birth weight neonates

Early Hum Dev. 2015 Jun;91(6):367-72. doi: 10.1016/j.earlhumdev.2015.03.008. Epub 2015 Apr 25.


Background and aims: Serum creatinine is traditionally used as a marker of renal function in neonates and relates to gestational age and disease severity in extremely low birth weight (ELBW) infants. Creatinine is commonly used as a biomarker for early morbidity, but we aim to compare postnatal creatinemia trends as a biomarker for subsequent cognitive outcome. We hypothesize that impaired microcirculation not only in the kidney, but also in general (i.e. brain development) can explain this possible link.

Study design and outcome measures: A cohort of ELBW infants was analyzed by Bayley Scales of Infant Development (BSID-II) at the corrected age of 2years old. Besides other perinatal indicators, neonatal creatinemia trends of survivors (n=140) and BSID scores (n=96) are compared and analyzed using optimal matching analysis. Hierarchical clustering analysis is applied to identify createnimia trends.

Results: Four different creatinemia trends were identified (persistently high, normal, low, high but normalizing). A low creatinemia trend is significantly associated with the lowest percentages of postnatal corticosteroids, NSAIDS and intraventricular hemorrhage (p=0.005, p=0.013 and p=0.041 respectively) compared to a normal or persistently high creatinemia trend and associated with the best cognitive outcome (+13 points compared to the mean creatinemia trend and +23 points compared to a persistently high creatinemia trend).

Conclusions: Creatinemia trends after birth are not only useful to predict renal function, but are also associated with cognitive outcome in extremely low birth weight infants. Neonates who have low creatinemia trends after birth, have the highest BSID scores at the age of two years old.

Keywords: Bayley Scales of Infant Development (BSID); Biomarker; Long term outcome; Optimal matching.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Child Development / physiology*
  • Cluster Analysis
  • Cognition / physiology*
  • Cohort Studies
  • Creatinine / blood*
  • Humans
  • Infant, Extremely Low Birth Weight / blood*
  • Infant, Extremely Low Birth Weight / physiology*
  • Infant, Newborn
  • Microcirculation / physiology*
  • Statistics, Nonparametric


  • Biomarkers
  • Creatinine