Association of circulating pro- and anti-inflammatory protein biomarkers in the first two postnatal weeks with brain MRI volumes and cognitive function at age 10 years in extremely preterm born children

Karl C K Kuban, Hernan Jara, T Michael O’Shea, Timothy Heeren, Robert M Joseph, Raina N Fichorova, Khalid Alshamrani, Adam Aakil, Forrest Beaulieu, Mitchell Horn, Laurie M Douglass, Jean A Frazier, Deborah Hirtz, Julie Vanier Rollins, David Cochran, Nigel Paneth, ELGAN Study Investigators

J Perinatol. 2019;210:81-90.

PubMed Link

To examine elevated neonatal inflammatory and neurotrophic proteins in relation to age-ten brain MRI volumes and cognition in children born extremely preterm.

Adjusting for GA and sex. Children with 3+ elevated IPs had smaller GM, brain stem/cerebellar (CBBS), and total brain (TB) volumes than those without elevated IPs, controlling for NTPs. Controlling for IPs, compared to children with no NTPs, those with 4+ NTPs had larger GM and TB volumes.  Higher GM, WM and CBBS volumes were significantly correlated with higher IQ. Grey and WM volumes were correlated with each other (r=-0.18, p=0.021), and CBBS was highly correlated with GM (r=0.55, p<0.001) and WM (r=0.29, p<0.001). Adjusting for other compartments, CBBS was associated with IQ (p=0.016), but association with WM was marginally significant. GM was not associated with IQ. Controlling for brain volumes, elevated IPs remained significantly associated with lower IQ, while elevated NTPs remained associated with higher IQ. Conclusion: Newborn IP and NP levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.