Research Areas

In her research, Dr. Bearer examines the mechanism that explains why drinking even the smallest amount of alcohol during pregnancy can result in fetal alcohol spectrum disorder, the most common cause of neurodevelopmental disability. Dr. Bearer and her team of researchers have identified fatty acid ethyl esters as a functional biomarker to determine which babies are exposed to ethanol. Dr. Bearer invented a technique to track ethanol exposure by analyzing the compounds in meconium, the first stools babies pass after they're born, which accumulate in utero during the third trimester. This biomarker is key in showing a correlation between ethanol exposure and neurodevelopment outcomes in neonates.

While many laboratories look at rescue treatment for infants already exposed to ethanol, Dr. Bearer is working to make fetuses and infants more resilient to that exposure. In basic research studies, she and her team have found that choline, an essential nutrient found in egg yolks and other food sources, acts as a neuroprotective agent against the effects of ethanol.

In this research, Dr. Bearer and her team treated cells with choline and then exposed them to ethanol. Results showed that choline decreases the impact of ethanol on biochemical indices of lipid rafts. Further studies treating neonatal rats confirmed the neuroprotection of choline on ethanol disrupted behavior. Dr. Bearer and her team hypothesize that choline increases the ability of lipid rafts to resist the disruptive effects of neurotoxicants like ethanol.

The findings have been extended to the study of bilirubin, another lipophilic agent, with a proposed similar mechanism for neurotoxicity. The initial studies led by Dr. Bearer have shown that choline supplementation prior to exposure reduces the impact of hyperbilirubinemia, a condition that commonly affects preterm infants and can hinder normal neurodevelopment. 

Combined, the studies of choline highlight the compound’s multi-functional and multi-mechanistic properties and underscore its potential application as a preventative nutritional supplement for both mothers and neonates.

Infants born prematurely may have high levels of bilirubin, which can result in neurotoxicity and hinder brain and neurodevelopment. To improve care for these infants, Dr. Bearer is studying whether choline supplementation in pregnant women and preterm babies improves infant resilience to the effects of bilirubin.

Broadly, Dr. Bearer and her team are investigating how the properties of lipophilic chemicals, like bilirubin, affect the ability of lipid raft-dependent proteins to mediate differentiation of these neurons. Using animal models of hyperbilirubinemia, Dr. Bearer has shown that bilirubin disrupts the function of lipid rafts associated with development of the cerebellum and brainstem. She has likewise demonstrated that choline supplementation decreases the disruption of the lipid rafts, vastly improving the behavior of these animals on several behavioral tests. Future research will examine the mechanisms that enable choline to prevent or counter bilirubin toxicity.

In expanded research Dr. Bearer and her team are investigating potential links between choline levels and social determinants of health. They are collecting the discarded blood from the first blood draw of infants at 24 to 28 weeks.The amount of choline in the blood samples is measured and compared to data extracted from medical records regarding social determinants of health. The aim of the research is to identify if there are any social determinants of health that determine choline concentrations and to see if choline supplementation is warranted in populations negatively affected by social determinants of health.

Pregnant women are commonly choline deficient, and it’s been reported that preterm infants are commonly choline deficient and become even more deficient when they are in the NICU. However, the current standard of care does not require choline supplementation.

Future research will likely include a choline supplementation program in a randomized controlled clinical trial to show if choline supplementation might be the next step in achieving better outcomes in preterm babies.

Dr. Bearer and her team are at the forefront of studying the role of lipid rafts in cerebellar and brain stem function, including respiratory control and audition. They have linked lipid raft dysfunction to decreased neurodevelopment. The research is significant as few labs focus on the function of lipid rafts in the development of the central nervous system during a critical period of human development.

Lipid rafts are microdomains within the plasma membrane that attract signaling molecules to come together on this platform so that they can signal to each other. This signaling is especially important in brain development. Of particular interest to Dr. Bearer are the lipid rafts at the end of growth cones of neurons that are extending axons to synapse on another neuron, and therefore create the correct “wiring” of the brain.

Dr. Bearer’s initial experiments looked at cell culture and found that ethanol exposure impaired the ability of proteins that were dependent on lipid rafts to traffic through the lipid raft and therefore impaired their downstream signaling. Additional studies on animal models have confirmed this observation.   

Understanding the function of lipid rafts and the impact of neurotoxins is essential for identifying new clinical interventions to improve and maximize potential clinical outcomes. The lab is now focused on specifically determining that lipophilic neurotoxicants target lipid rafts, and that lipid raft disruption leads to adverse outcomes.

During early postnatal life, evidence of immature respiratory control areas of the brain manifests as periodic breathing and apnea and can be accompanied by bradycardia and/or intermittent hypoxemia (IH). Therefore, low-risk interventions are needed to induce maturation of neuronal networks and stabilize respiration, reduce fluctuations in oxygenation, and minimize risk of neuronal impairment.

Dr. Bearer leads teams at Case Western Reserve University and University Hospitals (UH) Rainbow Babies & Children’s Hospital that are studying how the provision of an auditory environmental which is like that of the womb stimulates brainstem development in preterm infants.

The goal of the “The Effect of Sound on Maturation of Respiratory Control in Preterm Infants” research study is to characterize the acute effect of early postnatal sound exposure on neuronal function of the respiratory control regions of the brain in preterm infants. This important research lays the foundation for further development of actual womb and maternal voice recordings containing components that closely mimic the womb environment during 33-34 weeks of gestation, a proposed therapeutic window of brain development.

The researchers are using sound recordings to provide low-risk intervention to stabilize respiration, reduce IH, and induce functional maturation of neuronal respiratory networks during this critical stage of development. Ultimately, this earlier maturation could allow preterm infants to be discharged sooner to home, reducing hospital length of stay and improving mother-infant (or father-infant) interactions.

The researchers hypothesize that exposure to appropriately designed womb-like sounds in the UH Rainbow Babies & Children’s Hospital NICU will induce a more mature and stabilized cardiorespiratory pattern manifesting as a decrease in cardiorespiratory events, including apnea, bradycardia, IH, and mean/variance of heart rate.  This innovative approach could lead to crucial improvements in infant care protocols and developmental outcomes nationally, even internationally.