New Neonatology Chief at UH Rainbow Aims to Better Understand Protect, the Developing Brain

Cynthia F. Bearer, MD, PhD an expert on neurotoxicants – both known and lesser-known

Innovations in Pediatrics | Winter 2020

Cynthia Bearer, MD, PhD

Cynthia F. Bearer, MD, PhD, William and Lois Briggs Chair in Neonatology, Division Chief, Neonatology, UH Rainbow Babies & Children’s Hospital; Professor of Pediatrics, Adjunct Professor of Neurosciences and Environmental Health Sciences, Case Western Reserve University School of Medicine, has spent her career merging the fields of biochemistry and neonatology, teasing out the mechanisms behind neurotoxic insults to developing brain and how best to prevent or ameliorate them.

She began her career as a neonatologist at UH Rainbow Babies & Children’s Hospital in 1994, spending 14 years until her departure to become Chief of the Division of Neonatology at the University of Maryland, where she served for 11 years. Now she’s back at UH Rainbow as Chief of Neonatology – and she’s enthusiastic about continuing the basic-translational research that informs patient care -- research that she began here more than 25 years ago.

Neurotoxicants are the common thread.

“I’m very interested in how the brain develops, and I started that work by looking at chemical exposures to pregnant women and focused on alcohol,” she says. “Initially my research was looking at fetal alcohol spectrum disorder and fetal alcohol syndrome. I obtained a patent on a method using infant meconium to analyze metabolites of ethanol that indicate that the baby had been exposed to alcohol during pregnancy.”

More recently, Dr. Bearer has expanded her focus to other, less obvious alcohol exposures.

“In the NICU, you wouldn’t think that preterm babies would be exposed to alcohol,” she says. “But they are actually on occasion highly exposed to alcohol. There are the hand sanitizers that we use, particularly if we don’t have it completely evaporated before we put our hands in the isolette. But there are also the excipients that dissolve drugs so that we can give them intravenously. We’ve shown that there are high levels of alcohol biomarkers in the urine of these babies who have gotten a drug containing an alcohol excipient.”

“This is definitely something we as neonatologists can work on,” she adds. “There are alcohol-free preparations of some of these medications. Having a message in the EMR when you order a drug that you’re also delivering a dose of alcohol when you give this drug – that’s another solution. There are lots of different ways to handle it.”

Beyond documenting infant exposures to alcohol, Dr. Bearer has also delved deeply into the biochemical mechanisms by which alcohol – and other neurotoxicants -- affect brain development, looking closely at the vitally important L1 cell adhesion molecule. The important concept here, Dr. Bearer says, is the lipid raft – a specialized microdomain of the plasma membrane that serves as a platform for protein-protein interactions.

“At very low levels of alcohol, L1’s ability to stimulate neurite outgrowth is impaired,” she says. “So we began to ask ourselves why. It turns out that L1 has to traffic through a part of the leading edge of those nerve cells as they’re trying to find their synapse partner. They have to traffic through the lipid raft. We found that alcohol disturbed L1’s trafficking through the lipid raft and disrupted all the downstream signaling events that L1 needed to do. At the same time, we found that if we supplemented experimental animals with choline, we could prevent these effects on L1 and improve the animals’ behavior.”

Dr. Bearer received funding from the National Institute on Alcohol Abuse and Alcoholism to complete this work. Currently, she has funding from the National Institute of Child Health and Human Development to examine whether a similar mechanism might be at play with hyperbilirubinemia, which occurs in nearly all preterm newborns, sometimes causing hearing and movement disorders.

“Bilirubin is a known neurotoxicant,” she says. “But despite its high prevalence, the mechanisms underlying the effects of unconjugated free bilirubin on neuronal function are poorly understood. The affinity of free bilirubin with neuronal phospholipids suggests that lipid rafts might be a major target in hyperbilirubinemia.”

So far, Dr. Bearer says, her results suggest that this is the case.

“Our preliminary results show that bilirubin inhibits lipid raft function using L1 as a reporter,” she says. ”With our rats, we then found that if we supplemented them with choline, we could ameliorate a lot of the behavioral difficulties they were experiencing from the bilirubin. Now we’re doing a lot of the studies we did with alcohol – using bilirubin with our cultured cells and using this animal model of preterm exposure to hyperbilirubinemia.”

In her new role at UH Rainbow, Dr. Bearer says she will seek to promote this and other such research so that it can ultimately make a difference for her tiny patients and their families.

“One of my visions is to further develop the basic-translational research mission of the Division of Neonatology here at UH Rainbow,” she says. “For example, with my choline work – it works in animals and works in cell cultures. When can we move that to looking at whether babies are getting enough choline? I don’t think they are – I think they’re choline-deficient. Working with nutritionists on how we can deliver more choline to our babies and improving outcomes that way -- that’s what I’m interested in.”

For more information about Dr. Bearer and her research, please email Peds.Innovations@UHhospitals.org.