Prematurity Pediatric Research and Clinical Trials

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Premature infants and ventilators

Premature babies often need to be placed on ventilators, but these life-saving machines can sometimes damage their delicate lungs. In recent experiments in mice, stem cells taken from bone marrow and injected into the blood provided partial protection: the lungs' blood vessels were better maintained and inflammation was reduced.

Even when fluid in which the cells (known as bone marrow stromal cells) were grown was able to protect the lungs - in fact, better than the stem cells themselves. Stella Kourembanas, MD, former chief of Boston Children's Division of Newborn Medicine, believe this fluid, or certain proteins her lab has isolated within it, could become a future treatment to prevent preemies from developing chronic lung disease. She would also like to conduct follow-up experiments using stem cells taken from the umbilical cord, which can be obtained from infants in a less invasive manner than bone marrow cells.

Memantine and infant brains

Up to 35 percent of babies who survive prematurity are left with brain damage leading to cerebral palsy and cognitive/behavioral deficits. Now, neuroscientist Frances Jensen, MD, with Simon Manning, MD and Delia Talos, MD in the Department of Neurology and the Neurobiology Program, reports that memantine (Namenda), a drug originally developed for Alzheimer's disease, may reduce the damage.

For more than a decade, Jensen and others at Children's have shown that premature newborns rapidly developing brains have unique characteristics that not only heighten their vulnerability to hypoxia-ischemia (a common complication of prematurity that compromises the brains blood and oxygen supply), but also prevent these infants from responding to existing neurologic drugs. But Jensen has been finding new targets unique to the newborn brain—as well as drugs that can hit them, some of them already FDA-approved.

Now, in the June 25 Journal of Neuroscience, Jensen's team shows that preterm infants oligodendrocytes, the cells that form the brains white matter, are especially rich in NMDA receptors, a type of glutamate receptor. After a hypoxic-ischemic insult, glutamate builds up and can over-activate NMDA receptors, producing a pattern of white-matter injury known as periventricular leukomalacia (PVL), the most common cause of cerebral palsy.

However, working with a rat model of PVL, Jensen and colleagues found that giving memantine—which acts by blocking the NMDA receptor—significantly reduced white-matter injury after a hypoxic-ischemic insult. Back in the 1990s, Children's participated in memantines development as a treatment for Alzheimers disease. Now, if Jensen can establish the drugs safety in premature newborns, she wants to test it as a protective therapy.

Prematurity and autism

Extremely premature infants are known to have a high prevalence of learning disabilities, attention and behavioral problems. Premature infants born at less than 3.3 pounds have an increased risk for showing early signs of autistic characteristics, according to a Boston Children's Hospital study. "Early screening for autistic features might be warranted in this population," says researcher Catherine Limperopoulos, PhD, who cautions against drawing conclusions. "By no means are we suggesting all premature babies are at risk for autism.

Alternative ventilation for premature infants
Bernadette Levesque, MD, of the Division of Newborn Medicine at Children’s Hospital Boston led a study showing that mechanical ventilators can be hard on an infant’s lungs, and instead, encourage the use of “bubble” continuous positive airway pressure (bCPAP) system, which delivers a warmer, humidified oxygen that’s more gentle on an infant’s lungs. Learn more about the bCPAP system in the Children’s newsroom.
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