Researchers and clinicians from Boston Medical Center (BMC) have been awarded a four year, more than $13 million grant from the National Institutes of Health (NIH) to study neurological and brain abnormalities in former extremely low gestational age newborns (ELGANS). The study will be conducted under the direction of Karl Kuban, MD, chief of pediatric neurology at BMC, who also is the principal investigator of the study. BMC is the lead institution among 14 collaborating organizations across the country participating in this study.
The study, which is scheduled to begin later this month, will build on the ELGAN-1 prospective study of nearly a thousand ELGANs who were evaluated following birth and again at 2 years of age. Of those, 11 percent had cerebral palsy, 40 percent had a developmental quotient below 70, and 11 percent had microcephaly.
As part of the ELGAN-1 study, placenta organisms and histologic characteristics and elevated blood concentrations of proteins during the first postnatal weeks predicted 2-year cognitive and motor impairments and microcephaly. Additionally, 21 percent screened positive for autism spectrum disorders at 2 years.
"Our primary hypothesis is that at 10 years, former ELGANs who had elevated blood concentrations of inflammation-associated biomarkers in the first 2 postnatal weeks are more likely than other former ELGANs to have cognitive, behavioral and neurological disorders and brain structural abnormalities," explained Kuban who also is professor of pediatrics and neurology at Boston University School of Medicine. Ten years was chosen as an age when early adverse neurological problems often manifest with long-term and identifiable educational and quality of life consequences.
The Elgan-2 study will evaluate nearly 1,000 10 year-old ELGAN-1 participants at a dozen institutions in North Carolina, New England and the Midwest. Evaluations will entail direct participant testing and questionnaire/interview activities with the parent/guardian. About 20 percent of the cohort will return on a separate day for an added evaluation for autism (ADOS), and 20 percent will return on a separate day for a brain MRI study.
"In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our previous study was the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma. We hope to add to those findings thanks to the generosity of this NIH grant," Kuban said.
"We anticipate that this work will help establish a method for identifying infants at high risk as targets for clinical trials of prophylactic and therapeutic interventions. Ultimately, we hope that the result of our work will broaden and redirect the rationale for preventive and therapeutic interventions intended to reduce the risk and severity of neurodevelopmental disorders in ELGANs," added Kuban.