Brain development in micro-prem infants — Two studies

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Micro-premature infants who primarily consume breast milk have significantly higher levels of metabolites important for brain growth and development, according to a study presented at the Paediatric Academic Societies 2019 Annual Meeting. A separate study found that dietary lipids provide a much-needed brain boost by significantly increasing global brain volume as well as increasing volume in regions involved in motor activities and memory.

This. the first study, is according to sophisticated imaging conducted by an interdisciplinary research team at Childrens National.

“Our previous research established that vulnerable preterm infants who are fed breast milk early in life have improved brain growth and neuro-developmental outcomes. It was unclear what makes breastfeeding so beneficial for new-borns’ developing brains,” says Dr Catherine Limperopoulos, director of MRI Research of the Developing Brain at Children’s National. “Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites essential for growth and answer that lingering question.”

According to the US Centres for Disease Control and Prevention, about 1 in 10 US infants is born preterm. The Children’s research team presented their findings during the Paediatric Academic Societies 2019 Annual Meeting.

The research-clinicians enrolled babies who were very low birthweight (less than 1,500 grams) and 32 weeks gestational age or younger at birth when they were admitted to Children’s neonatal intensive care unit in the first week of life. The team gathered data from the right frontal white matter and the cerebellum – a brain region that enables people to maintain balance and proper muscle coordination and that supports high-order cognitive functions.

Each chemical has its own a unique spectral fingerprint. The team generated light signatures for key metabolites and calculated the quantity of each metabolite. Of note:
Cerebral white matter spectra showed significantly greater levels of inositol (a molecule similar to glucose) for babies fed breast milk, compared with babies fed formula.

Cerebellar spectra had significantly greater creatine levels for breastfed babies compared with infants fed formula. And the percentage of days infants were fed breast milk was associated with significantly greater levels of both creatine and choline, a water soluble nutrient.

“Key metabolite levels ramp up during the times babies’ brains experience exponential growth,” says Katherine M Ottolini, the study’s lead author. “Creatine facilitates recycling of ATP, the cell’s energy currency. Seeing greater quantities of this metabolite denotes more rapid changes and higher cellular maturation. Choline is a marker of cell membrane turnover; when new cells are generated, we see choline levels rise.”

Already, Children’s National leverages an array of imaging options that describe normal brain growth, which makes it easier to spot when foetal or neonatal brain development goes awry, enabling earlier intervention and more effective treatment. “Proton magnetic resonance spectroscopy may serve as an important additional tool to advance our understanding of how breastfeeding boosts neuro-development for preterm infants,” Limperopoulos adds.

 

Dietary lipids, already an important source of energy for tiny preemies, also provide a much-needed brain boost by significantly increasing global brain volume as well as increasing volume in regions involved in motor activities and memory, according to more research presented during the Paediatric Academic Societies 2019 Annual Meeting.

“Compared with macronutrients like carbohydrates and proteins, lipid intake during the first month of life is associated with increased overall and regional brain volume for micro-preemies,” says Limperopoulos, the senior author. “Using non-invasive magnetic resonance imaging, we see increased volume in the cerebellum by 2 weeks of age. And at four weeks of life, lipids increase total brain volume and boost regional brain volume in the cerebellum, amygdala-hippocampus and brainstem.”

The cerebellum is involved in virtually all physical movement and enables coordination and balance. The amygdala processes and stores short-term memories. The hippocampus manages emotion and mood. And the brainstem acts like a router, passing messages from the brain to the rest of the body, as well as enabling essential functions like breathing, a steady heart rate and swallowing.

According to the US Centres for Disease Control and Prevention, about 1 in 10 US babies is born preterm, or before 37 weeks gestation. Regions of the brain that play vital roles in complex cognitive and motor activities experience exponential growth late in pregnancy, making the developing brains of preterm infants particularly vulnerable to injury and impaired growth.

Children’s research faculty examined the impact of lipid intake in the first month of life on brain volumes for very low birth weight infants, who weighed 1,500 grams or less at birth. These micro-preemies are especially vulnerable to growth failure and neurocognitive impairment after birth.

The team enrolled 68 micro-preemies who were 32 weeks gestational age and younger when they were admitted to Children’s neonatal intensive care unit during their first week of life. They measured cumulative macronutrients – carbohydrates, proteins, lipids and calories – consumed by these new-borns at 2 and 4 weeks of life. Over years, Limperopoulos’ lab has amassed a large database of babies who were born full-term; this data provides unprecedented insights into normal brain development and will help to advance understanding of brain development in high-risk preterm infants.

“Even after controlling for average weight gain and other health conditions, lipid intake was positively associated with cerebellar and brainstem volumes in very low birthweight preterm infants,” adds Katherine M Ottolini, the study’s lead author.

According to Limperopoulos, Children’s future research will examine the optimal timing and volume of lipids to boost neurodevelopment for micro-preemies.

 

Abstracts
Not yet available online

Authors
Katherine M Ottolini; Nickie Andescavage; Kushal Kapse; Catherine Limperopoulos

Children’s National Health System material
Children’s National Health System material


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