Brain Chemical Ratios Help Predict Developmental Delays in Preterm Infants

Researchers have identified a potential biomarker for predicting whether a premature infant is at high risk for motor development problems, according to a study published online in the journal Radiology.

"We are living in an era in which survival of premature birth is more common," said Giles S. Kendall, Ph.D., consultant for the neonatal intensive care unit at University College London Hospitals NHS Foundation Trust and honorary senior lecturer of neonatal neuroimaging and neuroprotection at the University College London. "However, these infants continue to be at risk for neurodevelopmental problems."

Patients in the study included 43 infants (24 male) born at less than 32 weeks gestation and admitted to the neonatal intensive care unit (NICU) at the University College of London between 2007 and 2010. Dr. Kendall and his research team performed magnetic resonance imaging (MRI) and MR spectroscopy (MRS) exams on the infants at their approximate expected due dates (or term-equivalent age). MRS measures chemical levels in the brain.

The imaging studies were focused on the white matter of the brain, which is composed of nerve fibers that connect the functional centers of the brain.

"The white matter is especially fragile in the newborn and at risk for injury," Dr. Kendall explained.

One year later, 40 of the 43 infants were evaluated using the Bayley Scales of Infant and Toddler Development, which assess fine motor, gross motor and communication abilities. Of the 40 infants evaluated, 15 (38 percent) had abnormal composite motor scores and four (10 percent) showed cognitive impairment.

Statistical analysis of the MRS results and Bayley Scales scores revealed that the presence of two chemical ratios—increased choline/creatine (Cho/Cr) and decreased N-acetylaspartate/choline (NAA/Cho)—at birth were significantly correlated with developmental delays one year later.

"Low N-acetylaspartate/choline and rising choline/creatine observed during MRS at the baby’s expected due date predicted with 70 percent certainty which babies were at high risk for motor development problems at one year," Dr. Kendall said.

Dr. Kendall said a tool to predict the likelihood of a premature baby having neurodevelopmental problems would be useful in determining which infants should receive intensive interventions and in testing the effectiveness of those therapies.

"Physiotherapy interventions are available but are very expensive, and the vast majority of premature babies don’t need them," Dr. Kendall said. "Our hope is to find a robust biomarker that we can use as an outcome measure so that we don’t have to wait five or six years to see if an intervention has worked."

Dr. Kendall said severe disability associated with premature births has decreased over the past two decades as a result of improved care techniques in the NICU. However, many premature infants today have subtle abnormalities that are difficult to detect with conventional MRI.

"There’s a general shift away from simply ensuring the survival of these infants to how to give them the best quality of life," he said. "Our research is part of an effort to improve the outcomes for prematurely born infants and to identify earlier which babies are at greater risk."

Brain chemistry changes in children with autism offer clues to earlier detection and intervention

Between ages three and 10, children with autism spectrum disorder exhibit distinct brain chemical changes that differ from children with developmental delays and those with typical development, according to a new study led by University of Washington researchers.

The finding that early brain chemical alterations tend to normalize during the course of development in children with ASD gives new insight to efforts to improve early detection and intervention. The findings were reported July 31 in the Journal of the American Medical Assocation Psychiatry.

“In autism, we found a pattern of early chemical alterations at the cellular level that over time resolved – a pattern similar to what others have seen with people who have had a closed head injury and then got better,” said Stephen R. Dager, a UW professor of radiology and adjunct professor of bioengineering and associate director of UW’s Center on Human Development and Disability.

Neva Corrigan, a senior research fellow in radiology, was first author and Dager corresponding author of the study, titled “Atypical Developmental Patterns of Brain Chemistry in Children with Autism Spectrum Disorder.”

“The brain developmental abnormalities we observed in the children with autism are dynamic, not static. These early chemical alterations may hold clues as to specific processes at play in the disorder and, even more exciting, these changes may hold clues to reversing these processes,” Dager said.

In the study, scientists compared brain chemistry among three groups of children: those with a diagnosis of ASD, those with a diagnosis of developmental delay, and those considered typically developing. The researchers used magnetic resonance spectroscopic imaging, a type of MRI, to measure tissue-based chemicals in three age groups: 3-4 years, 6-7 years and 9-10 years.

One of the chemicals measured, N-acetylaspartate (NAA), is thought to play an important role in regulating synaptic connections and myelination. Its levels are decreased in people with conditions such as Alzheimer’s, traumatic brain injury or stroke. Other chemicals examined in the study – choline, creatine, glutamine/glutamate and myo-inositol – help characterize brain tissue integrity and bioenergetic status.

A notable finding concerned changes in gray matter NAA concentration: In scans of the 3- to 4-year-olds, NAA concentrations were low in both the ASD and developmentally delayed groups. By 9 to 10 years, NAA levels in the children with ASD had caught up to the levels of the typically developing group, while low levels of NAA persisted in the developmentally delayed group.

“A substantial number of kids with early, severe autism symptoms make tremendous improvements. We’re only measuring part of the iceberg, but this is a glimmer that we might be able to find a more specific period of vulnerability that we can measure and learn how to do something more proactively,” said Annette Estes, a co-author of the study and director of the UW Autism Center. She is an associate professor of speech and hearing sciences.

Study co-author Dennis Shaw, a UW professor of radiology and director of MRI at Seattle Children’s, observed that the findings “parallel some of the early brain structural differences we and others have found on MRI that also appear to normalize over time in children with autism. These chemical findings will help to better establish the timing and mechanisms underlying genetic abnormalities known to be involved in at least some cases of autism.”

Dager and UW colleagues are currently using more advanced MRI methods to study infants at risk for ASD because of an older sibling with autism.

“We’re looking prospectively at these children starting at 6 months to determine if we can detect very early alterations in brain cell signaling or related cellular disruption that may precede early, subtle clinical symptoms of ASD.”

Despite the encouraging finding, science has yet to pinpoint the when, what and why of autism’s inception, an event often likened to the flipping of a switch. Discovering the earliest period that a child’s brain starts to develop a profile of ASD is crucial because, as the study acknowledged, “even a relatively brief period of abnormal signaling between glial cells and neurons during early development would likely have a lasting effect” on how a child’s brain network develops.

This study also suggests that developmental delay and autism spectrum disorder are distinct disorders having different underlying brain mechanisms and treatment considerations, Dager said.

“Autism appears to have a different pathophysiology and different early biological course than idiopathic developmental disorder. There are differences in their underlying biological processes; this supports the notion that ASD is different from developmental delay and challenges the notion that the increasing prevalence of autism merely reflects a re-categorization of symptoms between autism and intellectual disabilities.”

Choline intake improves memory and attention-holding capacity

An experimental study in rats has shown that consuming choline, a vitamin B group nutrient found in foodstuffs like eggs and chicken or beef liver, soy and wheat germ, helps improve long-term memory and attention-holding capacity. The study, conducted by scientists at the University of Granada (Spain) Simón Bolívar University, (Venezuela) and the University of York (United Kingdom), has revealed that choline is directly involved in attention and memory processes and helps modulate them.

Researchers studied the effects of dietary supplements of choline in rats in two experiments aimed at analysing the influence of vitamin B intake on memory and attention processes during gestation and in adult specimens.

In the first experiment, scientists administered choline to rats during the third term of gestation in order to determine the effect of prenatal choline on the memory processes of their offspring. Three groups of pregnant rats were fed choline-rich, standard or choline-deficient diets. When their offspring had reached adult age, a sample of 30 was selected: 10 were female offspring of dams fed a choline-supplement, 10 had followed a choline-deficient diet and the other 10, a standard diet, acting as a control group.

Long-term memory

This sample of adult offspring underwent an experiment to measure their memory retention: 24 hours after being shown an object all the offspring (whether in the choline-supplement group or not) remembered it and it was familiar to them However, after 48 hours, the rats of dams fed a prenatal choline-rich diet recognized the object better than those in the standard diet group, while the choline-deficient group could not recognize it. Thus, the scientists concluded that prenatal choline intake improves long-term memory in the resulting offspring once they reach adulthood.

In the second experiment, the researchers measured changes in attention that occurred in adult rats fed a choline supplement for 12 weeks, versus those with no choline intake. They found that the rats which had ingested choline maintained better attention that the others when presented with a familiar stimulus. The control group, fed a standard diet, showed the normal learning delay when this familiar stimulus acquired a new meaning. However, the choline-rich intake rats showed a fall in attention to the familiar stimulus, rapidly learning its new meaning.

The study has been undertaken by University of Granada Department of Experimental Psychology researchers Isabel De Brugada-Sauras and Hayarelis Moreno-Gudiño (also on the research staff of Simón Bolívar University together with Diamela Carias); Milagros Gallo-Torre, researcher in the University of Granada Department of Psychobiology and Director of the “Federico Olóriz” University Research Institute for Neuroscience; and Geoffrey Hall, of the Department of Psychology of the University of York. Their study has recently given rise to publications in Nutritional Neuroscience and Behavioural Brain Research.

Sick from Stress? Blame Your Mom… And Epigenetics

If you’re sick from stress, a new research report appearing in the August 2012 issue of The FASEB Journal suggests that what your mother ate — or didn’t eat — may be part of the cause. The report shows that choline intake that is higher than what is generally recommended during pregnancy may improve how a child responds to stress. These improvements are the result of epigenetic changes that ultimately lead to lower cortisol levels. Epigenetic changes affect how a gene functions, even if the gene itself is not changed. Lowering cortisol is important as high levels of cortisol are linked to a wide range of problems ranging from mental health to metabolic and cardiovascular disorders.