Inflammatory Brain Damage in Preterm Newborns--Dry Numbers, Wet Lab, and Causal Inferences

Early Hum Dev. 2004 Aug;79(1):1-15. doi: 10.1016/j.earlhumdev.2004.04.009.


Epidemiologic observations support the contention that infection, inflammation, and neonatal white matter damage (WMD) are associated. We also have documentation from multiple experimental models that infection/inflammation can damage developing white matter. Based on these observations in humans and animals, we offer causal inferences using widely accepted causal criteria and the multivariable model of causation. As much as we want to, however, we are reluctant to state unequivocally that inflammation causes WMD in humans born much before term. The main reason is that we lack convincing evidence that inflammation precedes WMD (temporal evidence). We also need more (and more detailed) observational studies clarifying the presumed infection --> inflammation --> WMD sequence before we can initiate intervention trials to reduce the risk of WMD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain Diseases / epidemiology
  • Brain Diseases / etiology*
  • Cerebral Palsy / epidemiology
  • Cerebral Palsy / etiology
  • Chorioamnionitis / complications
  • Encephalitis / complications*
  • Encephalitis / epidemiology
  • Endometritis / complications
  • Female
  • Fetal Diseases
  • Fetus / blood supply
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Infections / complications
  • Pregnancy
  • Vasculitis / complications