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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Both antenatal and postnatal inflammation contribute information about the risk of brain damage in extremely preterm
Diana Yanni1, Steven J Korzeniewski2, Elizabeth N Allred3
1Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts.
Insights
Two inflammatory insults, antenatal (placental) and postnatal, significantly increase the risk of neurodevelopmental disorders in preterm newborns. This combined inflammation poses a greater threat than either insult alone.
Area of Science:
- Neonatal research
- Neuroscience
- Inflammation studies
Background:
- Intrauterine inflammation elevates preterm newborns' risk for neurodevelopmental disorders.
- The combined impact of antenatal and postnatal inflammation on adverse outcomes requires further investigation.
Purpose of the Study:
- To investigate the association between antenatal and postnatal inflammation and neurodevelopmental disorders in preterm infants.
- To determine if combined inflammatory insults amplify the risk of adverse outcomes.
Main Methods:
- Histologic placental inflammation defined antenatal inflammation.
- Seven inflammation-related proteins measured in blood on postnatal days 1, 7, and 14.
- Postnatal inflammation defined as protein concentration in the highest quartile on ≥2 days.
- Logistic regression models assessed inflammation's contribution to neurodevelopmental disorder risk.
Main Results:
- Placental inflammation followed by elevated C-reactive protein or ICAM-1 increased white matter damage risk.
- Placental inflammation plus elevated TNF-α or IL-8 heightened spastic cerebral palsy risk.
- Combined placental inflammation and elevated IL-6, TNF-α, or ICAM-1 increased microcephaly risk.
Conclusions:
- Two inflammatory insults ('hits') are associated with a stronger risk for abnormal cranial ultrasound, spastic cerebral palsy, and microcephaly at 2 years compared to a single inflammatory insult.
Abstract:
BackgroundPreterm newborns exposed to intrauterine inflammation are at an increased risk of neurodevelopmental disorders. We hypothesized that adverse outcomes are more strongly associated with a combination of antenatal and postnatal inflammation than with either of them alone.MethodsWe defined antenatal inflammation as histologic inflammation in the placenta. We measured the concentrations of seven inflammation-related proteins in blood obtained on postnatal days 1, 7, and 14 from 763 infants born before 28 weeks of gestation. We defined postnatal inflammation as a protein concentration in the highest quartile on at least 2 days. We used logistic regression models to evaluate the contribution of antenatal and postnatal inflammation to the risk of neurodevelopmental disorders.ResultsThe risk of white matter damage was increased when placental inflammation was followed by sustained elevation of C-reactive protein or ICAM-1. We found the same for spastic cerebral palsy when placental inflammation was followed by elevation of TNF-α or IL-8. The presence of both placental inflammation and elevated levels of IL-6, TNF-α, or ICAM-1 was associated with an increased risk for microcephaly.ConclusionCompared with a single hit, two inflammatory hits are associated with stronger risk for abnormal cranial ultrasound, spastic cerebral palsy, and microcephaly at 2 years.
