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Published on: November 20, 2015
Inflammatory brain damage in preterm newborns--dry numbers, wet lab, and causal inferences
1Perinatal Infectious Disease Epidemiology Unit, Hannover Medical School, Germany. dammann.olaf@mh-hannover.de
Insights
Infection and inflammation are linked to neonatal white matter damage (WMD). However, more research is needed to confirm inflammation definitively causes WMD in premature infants.
Area of Science:
- Neonatal neurology
- Neuroinflammation
- Developmental neuroscience
Background:
- Epidemiologic studies suggest a link between infection, inflammation, and neonatal white matter damage (WMD).
- Experimental models demonstrate that infection/inflammation can harm developing white matter in neonates.
Purpose of the Study:
- To evaluate the causal relationship between inflammation and neonatal white matter damage (WMD) in premature infants.
- To identify the need for further evidence, particularly temporal data, to establish inflammation as a direct cause of WMD.
Main Methods:
- Review of existing epidemiologic observations and experimental model data.
- Application of widely accepted causal criteria and multivariable models of causation.
- Assessment of the strength of evidence for a causal link, focusing on temporal sequence.
Main Results:
- While associations are supported, definitive causal inference that inflammation causes WMD in preterm infants is currently limited.
- A critical gap exists in demonstrating that inflammation precedes WMD (temporal evidence).
Conclusions:
- Further detailed observational studies are required to elucidate the infection --> inflammation --> WMD pathway.
- Establishing the temporal relationship is crucial before initiating intervention trials to mitigate WMD risk.
Abstract:
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.
