Hope for the Future: Neuroprotection of Preterm Infants
Washington, DC—The use of nanodevices to deliver anti-inflammatory agents to the neonatal, and perhaps the newborn, brain may alter the risk for cerebral palsy in preterm infants, according to cutting-edge research presented at the 2011 meeting of the American College of Obstetricians and Gynecologists.
Roberto J. Romero, MD, Chief, Perinatal Research Branch, National Institutes of Health, and Professor of Molecular Obstetrics and Genetics, Wayne State University, Detroit, MI, presented recent findings on the topic.
Dr Romero described the protective effects of magnesium sulfate, which have been recognized for some time. The 3 randomized, controlled trials that have studied this effect have arrived at different conclusions, he said. “The evidence from these was not clear, so our group looked carefully at the studies in a meta-analysis and found a persuasive trend,” he ex plained.
In a 2009 meta-analysis by Dr Romero and colleagues, the use of magnesium sulfate reduced the risk for cerebral palsy by 31%, including risk for severe cerebral palsy, without increasing pediatric mortality. The number of mothers needed to treat to prevent 1 case of cerebral palsy was 52, and the cost of prevention was just $197 per patient, he said.
Infection a Cause of Preterm Birth and Cerebral Palsy
The evidence is “compelling” that intrauterine infection and inflammation play a role in preterm labor and, therefore, in the development of cerebral palsy, Dr Romero said. In utero infection or inflammation accounts for about 20% of cases of cerebral palsy.
Bacterial infections are implicated in cerebral palsy. Specifically, infection or inflammation leads to periventricular leukomalacia, which leads to cerebral palsy, he said.
“The presence of funisitis at birth suggests the neonate was exposed to infection in utero, and this can be useful in the medicolegal setting,” he added. In other words, this condition suggests that cerebral palsy is not a result of birth injury.
Cerebral palsy appears to be associated with intra-amniotic infection and inflammation can be prevented. In neonatal animals, infusion of dendrimers (nanodevices) containing the anti-inflammatory agent N-acetyl - cysteine ameliorated neural inflammation, he said.
“Dendrimers preferentially localize in activated microglia and astrocytes (key cells in cerebral palsy),” Dr Romero said. “They behave like stem cells. You give them intravenously and they find their way to the neuroinflammation.” An experiment in pregnant rabbits with endotoxin-induced neuroinflammation produced a dramatic effect. At birth, littermates either remained untreated or were injected with dendrimers that release N-acetylcysteine. The untreated endotoxin-exposed rabbits exhibited motor symptoms of cerebral palsy, but animals who received the experimental treatment showed substantial improvement in motor coordination, demonstrated by a video accompanying Dr Romero’s presentation.
“I believe these experiments show that neuroinflammation can cause cerebral palsy, that molecular techniques can detect neuroinflammation at birth, and that using nanodevices, we can deliver anti-inflammatory agents to neonatal, and maybe newborn, brains, thus changing the development of cerebral palsy,” Dr Romero acknowledged.