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T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation

Maternal mental health alters structure and biochemistry of developing fetal brain

Even when pregnant women have uncomplicated pregnancies and high socioeconomic status, when they experience elevated anxiety, stress or depression these prenatal stressors can alter the structure of the developing fetal brain and disrupt its biochemistry, according to Children’s National Hospital research published online Jan. 29, 2020, in JAMA Network Open.

The Children’s National research findings “have enormous scientific, clinical and public health implications,” Charles A. Nelson III, Ph.D.,  Boston Children’s Hospital, writes in a companion editorial.

“Previously we found that 65% of pregnant women who received a diagnosis of fetal congenital heart disease had elevated levels of stress. It’s concerning but not surprising that pregnant women who wonder if their baby will need open heart surgery would feel stress,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s senior author. “In this latest study, we ran the same panel of questionnaires and were surprised to find a high proportion of otherwise healthy pregnant women whose unborn babies are doing well also report high levels of stress.”

Anxiety and depression are the most common mental health problems during pregnancy. To learn more about the implications for the developing fetal brain, the Children’s National research team recruited 119 healthy volunteers with low-risk pregnancies from obstetric clinics in Washington, D.C., from Jan. 1, 2016, to April 17, 2019. The women’s mean age was 34.4 years old. All were high school graduates, 83% were college graduates, and 84% reported professional employment.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation.

T2-Weighted Magnetic Resonance (MR) Imaging Brain Segmentation. Segmentation results of total brain (orange), cortical gray matter (green), white matter (blue), deep gray matter (brown), brainstem (yellow), cerebellum (light blue), left hippocampus (purple) and right hippocampus (red) on a 3-Dimensional reconstructed T2-weighted MR image of a fetus at 26.4 gestational weeks. The hippocampus plays a central role in memory and behavioral inhibition and contains high concentrations of corticosteroid receptors and, thus, this brain region is sensitive to stress. Credit: JAMA Network Open.

The team performed 193 fetal brain magnetic resonance imaging (MRI) sessions between 24-40 weeks gestation and measured the volume of the total fetal brain as well as the cortical gray matter, white matter, deep gray matter, cerebellum, brainstem and hippocampus volumes. On the same day as their MRI visit, the pregnant women completed validated questionnaires to measure maternal stress, anxiety and depression, answering questions such as “how do you feel right now,” “how do you generally feel” as well as the degree of stressful feelings they experienced the month prior.

Of the pregnant women in the study:

  • 27% tested positive for stress
  • 26% tested positive for anxiety
  • 11% tested positive for depression
  • Maternal anxiety and stress were associated with increased fetal cortical gyrification
  • Elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain
  • Maternal stress scores decreased with increasing gestational age, while anxiety and depression did not

“We report for the first time that maternal psychological distress may be associated with increased fetal local gyrification index in the frontal and temporal lobes,” says Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author. “We also found an association with left fetal hippocampal volume, with maternal psychological distress selectively stunting the left hippocampal volumetric growth more than the right. And elevated maternal depression was associated with decreased creatine and choline levels in the fetal brain,” Wu adds.

Late in pregnancy – at the time these women were recruited into the cohort study – the fetal brain grows exponentially and key metabolite levels also rise. Creatine facilitates recycling of adenosine triphosphate, the cell’s energy currency. Typically, levels of this metabolite rise, denoting rapid changes and higher cellular maturation; creatine also is known to support cognitive function. Choline levels also typically rise, marking cell membrane turnover as new cells are generated and support memory, mental focus and concentration.

“These women were healthy, and of high socioeconomic status and educational level, leading us to conclude that the prevalence of prenatal maternal psychological distress may be underestimated,” Limperopoulos adds. “While stress is an everyday reality for most of us, this is different because elevated stress during pregnancy can alter fetal brain programming. Our findings underscore the critical need to universally screen all pregnant women for prenatal psychological distress, even young mothers whose pregnancies wouldn’t otherwise raise red flags.”

In addition to Limperopoulos and Wu, Children’s National study co-authors include Yuan-Chiao Lu, Ph.D., research associate; Marni Jacobs, Ph.D., biostatistician; Subechhya Pradhan, Ph.D., research faculty; Kushal Kapse, MS, staff engineer; Li Zhao, Ph.D., research faculty; Nickie Niforatos-Andescavage, M.D., neonatologist; Gilbert Vezina, M.D., director of the neuroradiology program; and Adré  J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Research coordinators Catherine Lopez, MS, Kathryn Lee Bannantine, BSN, and Jessica Lynn Quistorff, MPH, assisted with subject recruitment.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. RO1 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

Journal Reference:
Yao Wu, Yuan-Chiao Lu, Marni Jacobs, Subechhya Pradhan, Kushal Kapse, Li Zhao, Nickie Niforatos-Andescavage, Gilbert Vezina, Adré J. du Plessis, Catherine Limperopoulos. “Association of prenatal maternal psychological distress with fetal brain growth, metabolism and cortical maturation,” JAMA Network Open, 3(1): e1919940, 2020

Catherine Limperopoulos

Stressful pregnancies can leave fingerprint on fetal brain

Catherine Limperopoulos

“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author.

When a diagnosis of fetal congenital heart disease causes pregnant moms to test positive for stress, anxiety and depression, powerful imaging can detect impaired development in key fetal brain regions, according to Children’s National Hospital research published online Jan. 13, 2020, in JAMA Pediatrics.

While additional research is needed, the Children’s National study authors say their unprecedented findings underscore the need for universal screening for psychological distress as a routine part of prenatal care and taking other steps to support stressed-out pregnant women and safeguard their newborns’ developing brains.

“We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression,” says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children’s National and the study’s corresponding author. “Equally concerning is how prevalent psychological distress is among pregnant women generally. We report for the first time that this challenging prenatal environment impairs regions of the fetal brain that play a major role in learning, memory, coordination, and social and behavioral development, making it all the more important for us to identify these women early during pregnancy to intervene,” Limperopoulos adds.

Congenital heart disease (CHD), structural problems with the heart, is the most common birth defect. Still, it remains unclear how exposure to maternal stress impacts brain development in fetuses with CHD.

The multidisciplinary study team enrolled 48 women whose unborn fetuses had been diagnosed with CHD and 92 healthy women with uncomplicated pregnancies. Using validated screening tools, they found:

  • 65% of pregnant women expecting a baby with CHD tested positive for stress
  • 27% of women with uncomplicated pregnancies tested positive for stress
  • 44% of pregnant women expecting a baby with CHD tested positive for anxiety
  • 26% of women with uncomplicated pregnancies tested positive for anxiety
  • 29% of pregnant women expecting a baby with CHD tested positive for depression and
  • 9% women with uncomplicated pregnancies tested positive for depression

All told, they performed 223 fetal magnetic resonance imaging sessions for these 140 fetuses between 21 and 40 weeks of gestation. They measured brain volume in cubic centimeters for the total brain as well as volumetric measurements for key regions such as the cerebrum, cerebellum, brainstem, and left and right hippocampus.

Maternal stress and anxiety in the second trimester were associated with smaller left hippocampi and smaller cerebellums only in pregnancies affected by fetal CHD. What’s more, specific regions — the hippocampus head and body and the left cerebellar lobe – were more susceptible to stunted growth. The hippocampus is key to memory and learning, while the cerebellum controls motor coordination and plays a role in social and behavioral development.

The hippocampus is a brain structure that is known to be very sensitive to stress. The timing of the CHD diagnosis may have occurred at a particularly vulnerable time for the developing fetal cerebellum, which grows faster than any other brain structure in the second half of gestation, particularly in the third trimester.

“None of these women had been screened for prenatal depression or anxiety. None of them were taking medications. And none of them had received mental health interventions. In the group of women contending with fetal CHD, 81% had attended college and 75% had professional educations, so this does not appear to be an issue of insufficient resources,” Limperopoulos adds. “It’s critical that we routinely to do these screenings and provide pregnant women with access to interventions to lower their stress levels. Working with our community partners, Children’s National is doing just that to help reduce toxic prenatal stress for both the health of the mother and for the future newborns. We hope this becomes standard practice elsewhere.”

Adds Yao Wu, Ph.D., a research associate working with Limperopoulos at Children’s National and the study’s lead author: “Our next goal is exploring effective prenatal cognitive behavioral interventions to reduce psychological distress felt by pregnant women and improve neurodevelopment in babies with CHD.”

In addition to Limperopoulos and Wu , Children’s National study co-authors include Kushal Kapse, MS, staff engineer; Marni Jacobs, Ph.D., biostatistician; Nickie Niforatos-Andescavage, M.D., neonatologist; Mary T. Donofrio, M.D., director, Fetal Heart Program; Anita Krishnan, M.D., associate director, echocardiography; Gilbert Vezina, M.D., director, Neuroradiology Program; David Wessel, M.D., Executive Vice President and Chief Medical Officer; and Adré  J. du Plessis, M.B.Ch.B., director, Fetal Medicine Institute. Jessica Lynn Quistorff, MPH, Catherine Lopez, MS, and Kathryn Lee Bannantine, BSN, assisted with subject recruitment and study coordination.

Financial support for the research described in this post was provided by the National Institutes of Health under grant No. R01 HL116585-01 and the Thrasher Research Fund under Early Career award No. 14764.

sleeping baby

False negatives: Delayed Zika effects in babies who appeared normal at birth

sleeping baby

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants.

Colombian infants exposed to Zika virus in the womb showed neurodevelopmental delays as toddlers, despite having “normal” brain imaging and head circumference at birth, a finding that underscores the importance of long-term neurodevelopmental follow-up for Zika-exposed infants, according to a cohort study published online Jan. 6, 2020, in JAMA Pediatrics.

“These infants had no evidence of Zika deficits or microcephaly at birth. Neurodevelopmental deficits, including declines in mobility and social cognition, emerged in their first year of life even as their head circumference remained normal,” says Sarah B. Mulkey, M.D. Ph.D., a fetal/neonatal neurologist at Children’s National Hospital and the study’s first author. “About one-third of these newborns who underwent postnatal head ultrasound had nonspecific imaging results, which we believe are the first published results finding a link between subtle brain injuries and impaired neuromotor development in Zika-exposed children.”

The multi-institutional research group led by Children’s National enrolled pregnant women in Atlántico Department, which hugs the Caribbean coast of Colombia, who had been exposed to Zika, and performed a series of fetal magnetic resonance images (MRI) and ultrasounds as their pregnancies progressed.

Even though their mothers had laboratory-confirmed Zika infections, 77 out of 82 of their offspring were born with no sign of congenital Zika syndrome, a constellation of birth defects that includes severe brain abnormalities, eye problems and congenital contractures, and 70 underwent additional testing of neurodevelopment during infancy. These apparently normal newborns were born between Aug. 1, 2016, and Nov. 30, 2017, at the height of the Zika epidemic, and had normal head circumference.

When they were 4 to 8 months or 9 to 18 months of age, the infants’ neurodevelopment was evaluated using two validated tools, the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (a 50-item test of such skills as self-care, mobility, communication and social cognition) and the Alberta Infant Motor Scale (a motor examination of infants in prone, supine, sitting and standing positions). Some infants were assessed during each time point.

Women participating in the study were highly motivated, with 91% following up with appointments, even if it meant traveling hours by bus. In addition to Children’s National faculty traveling to Colombia to train staff how to administer the screening instruments, videotaped assessments, MRIs and ultrasounds were read, analyzed and scored at Children’s National. According to the study team, the U.S. scoring of Alberta Infant Motor Scale tests administered in Colombia is also unprecedented for a research study and offers the potential of remote scoring of infants’ motor skill maturity in regions of the world where pediatric specialists, like child neurologists, are lacking.

“Normally, neurodevelopment in infants and toddlers continues for years, building a sturdy neural network that they later use to carry out complex neurologic and cognitive functions as children enter school,” Dr. Mulkey adds. “Our findings underscore the recommendations by the Centers for Disease Control and Prevention (CDC) that all infants exposed to Zika in the womb undergo long-term follow-up, providing an opportunity to intervene earlier.”

An accompanying editorial by CDC staffers concurs, saying the study reported “intriguing data” that add “to the growing evidence of the need for long-term follow-up for all children with Zika virus exposure in utero to ensure they receive the recommended clinical evaluations even when no structural defects are identified at birth.”

In addition to Dr. Mulkey, study co-authors include Margarita Arroyave-Wessel, MPH, Dorothy I. Bulas, M.D., chief of Diagnostic Imaging and Radiology, JiJi Jiang, MS, Stephanie Russo, BS, Robert McCarter, ScD, research section head, design and biostatistics,  Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, and co-Senior Author, Roberta L. DeBiasi, MD, MS, chief of the Division of Pediatric Infectious Diseases, all of Children’s National; Colleen Peyton, PT, DPT, of Northwestern University; Yamil Fourzali, M.D., of Sabbag Radiologos, Barranquilla, Colombia; Michael E. Msall, M.D., of University of Chicago Comer Children’s Hospital; and co-Senior Author, Carlos Cure, M.D., BIOMELab, Barranquilla, Colombia.

Funding for the research described in this post was provided by the Thrasher Research Fund, the National Institutes of Health under award Nos. UL1TR001876 and KL2TR001877, and the Leadership Education in Neurodevelopmental and Related Disorders Training Program under grant HRSA/MCHB T73 MC11047.

brain network illustration

$2.5M to protect the brain from metabolic insult

brain network illustration

The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, which makes this organ particularly vulnerable to changes in metabolism.

More than 30 million Americans have diabetes, with the vast majority having Type 2 disease. Characterized by insulin resistance and persistently high blood sugar levels, poorly controlled Type 2 diabetes has a host of well-recognized complications: compared with the general population, a greatly increased risk of kidney disease, vision loss, heart attacks and strokes and lower limb amputations.

But more recently, says Nathan A. Smith, MS, Ph.D., a principal investigator in Children’s National Research Institute’s Center for Neuroscience Research, another consequence has become increasingly apparent. With increasing insulin resistance comes cognitive damage, a factor that contributes significantly to dementia diagnoses as patients age.

The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, Smith explains – which makes this organ particularly vulnerable to changes in metabolism. Type 2 diabetes and even prediabetic changes in glucose metabolism inflict damage upon this organ in mechanisms with dangerous synergy, he adds. Insulin resistance itself stresses brain cells, slowly depriving them of fuel. As blood sugar rises, it also increases inflammation and blocks nitric oxide, which together narrow the brain’s blood vessels while also increasing blood viscosity.

When the brain’s neurons slowly starve, they become increasingly inefficient at doing their job, eventually succumbing to this deprivation. These hits don’t just affect individual cells, Smith adds. They also affect connectivity that spans across the brain, neural networks that are a major focus of his research.

While it’s well established that Type 2 diabetes significantly boosts the risk of cognitive decline, Smith says, it’s been unclear whether this process might be halted or even reversed. It’s this question that forms the basis of a collaborative Frontiers grant, $2.5 million from the National Science Foundation split between his laboratory; the lead institution, Stony Brook University; and Massachusetts General Hospital/Harvard Medical School.

Smith and colleagues at the three institutions are testing whether changing the brain’s fuel source from glucose to ketones – byproducts from fat metabolism – could potentially save neurons and neural networks over time. Ketones already have shown promise for decades in treating some types of epilepsy, a disease that sometimes stems from an imbalance in neuronal excitation and inhibition. When some patients start on a ketogenic diet – an extreme version of a popular fat-based diet – many can significantly decrease or even stop their seizures, bringing their misfiring brain cells back to health.

Principal Investigator Smith and his laboratory at the Children’s National Research Institute are using experimental models to test whether ketones could protect the brain against the ravages of insulin resistance. They’re looking specifically at interneurons, the inhibitory cells of the brain and the most energy demanding. The team is using a technique known as patch clamping to determine how either insulin resistance or insulin resistance in the presence of ketones affect these cells’ ability to fire.

They’re also looking at how calcium ions migrate in and out of the cells’ membranes, a necessary prerequisite for neurons’ electrical activity. Finally, they’re evaluating whether these potential changes to the cells’ electrophysiological properties in turn change how different parts of the brain communicate with each other, potentially restructuring the networks that are vital to every action this organ performs.

Colleagues at Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Harvard Medical School, led by Principal Investigator Eva-Maria Ratai, Ph.D.,  will perform parallel work in human subjects. They will use imaging to determine how these two fuel types, glucose or ketones, affect how the brain uses energy and produces the communication molecules known as neurotransmitters. They’re also investigating how these factors might affect the stability of neural networks using techniques that investigate the performance of these networks both while study subjects are at rest and performing a task.

Finally, colleagues at the Laufer Center for Physical and Quantitative Biology at Stony Brook University, led by Principal Investigator Lilianne R. Mujica-Parodi, Ph.D., will use results generated at the other two institutions to construct computational models that can accurately predict how the brain will behave under metabolic stress: how it copes when deprived of fuel and whether it might be able to retain healthy function when its cells receive ketones instead of glucose.

Collectively, Smith says, these results could help retain brain function even under glucose restraints. (For this, the research team owes a special thanks to Mujica-Parodi, who assembled the group to answer this important question, thus underscoring the importance of team science, he adds.)

“By supplying an alternate fuel source, we may eventually be able to preserve the brain even in the face of insulin resistance,” Smith says.

Andrea Gropman

$5M in federal funding to help patients with urea cycle disorders

Andrea Gropman

Andrea L. Gropman, M.D.: We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.

An international research consortium co-led by Andrea L. Gropman, M.D., at Children’s National Hospital has received $5 million in federal funding as part of an overall effort to better understand rare diseases and accelerate potential treatments to patients.

Urea cycle disorder, one such rare disease, is a hiccup in a series of biochemical reactions that transform nitrogen into a non-toxic compound, urea. The six enzymes and two carrier/transport molecules that accomplish this essential task reside primarily in the liver and, to a lesser degree, in other organs.

The majority of patients have the recessive form of the disorder, meaning it has skipped a generation. These kids inherit one copy of an abnormal gene from each parent, while the parents themselves were not affected, says Dr. Gropman, chief of the Division of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National. Another more common version of the disease is carried on the X chromosome and affects boys more seriously that girls, given that boys have only one X chromosome.

Regardless of the type of urea cycle disorder, when the urea cycle breaks down, nitrogen converts into toxic ammonia that builds up in the body (hyperammonemia), particularly in the brain. As a result, the person may feel lethargic; if the ammonia in the bloodstream reaches the brain in high concentrations, the person can experience seizures, behavior changes and lapse into a coma.

Improvements in clinical care and the advent of effective medicines have transformed this once deadly disease into a more manageable chronic ailment.

“It’s gratifying that patients diagnosed with urea cycle disorder now are surviving, growing up, becoming young adults and starting families themselves. Twenty to 30 years ago, this never would have seemed conceivable,” Dr. Gropman says. “We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.”

In early October 2019, the National Institutes of Health (NIH) awarded the Urea Cycle Disorders Consortium for which Dr. Gropman is co-principal investigator a five-year grant. This is the fourth time that the international Consortium of physicians, scientists, neuropsychologists, nurses, genetic counselors and researchers has received NIH funding to study this group of conditions.

Dr. Gropman says the current urea cycle research program builds on a sturdy foundation built by previous principal investigators Mendel Tuchman, M.D., and Mark Batshaw, M.D., also funded by the NIH. While previous rounds of NIH funding powered research about patients’ long-term survival prospects and cognitive dysfunction, this next phase of research will explore patients’ long-term health.

Among the topics they will study:

Long-term organ damage. Magnetic resonance elastrography (MRE) is a state-of-the-art imaging technique that combines the sharp images from MRI with a visual map that shows body tissue stiffness. The research team will use MRE to look for early changes in the liver – before patients show any symptoms – that could be associated with long-term health impacts. Their aim is spot the earliest signs of potential liver dysfunction in order to intervene before the patient develops liver fibrosis.

Academic achievement. The research team will examine gaps in academic achievement for patients who appear to be underperforming to determine what is triggering the discrepancy between their potential and actual scholastics. If they uncover issues such as learning difficulties or mental health concerns like anxiety, there are opportunities to intervene to boost academic achievement.

“And if we find many of the patients meet the criteria for depression or anxiety disorders, there are potential opportunities to intervene.  It’s tricky: We need to balance their existing medications with any new ones to ensure that we don’t increase their hyperammonemia risk,” Dr. Gropman explains.

Neurologic complications. The researchers will tap continuous, bedside electroencephalogram, which measures the brain’s electrical activity, to detect silent seizures and otherwise undetectable changes in the brain in an effort to stave off epilepsy, a brain disorder that causes seizures.

“This is really the first time we will examine babies’ brains,” she adds. “Our previous imaging studies looked at kids and adults who were 6 years and older. Now, we’re lowering that age range down to infants. By tracking such images over time, the field has described the trajectory of what normal brain development should look like. We can use that as a background and comparison point.”

In the future, newborns may be screened for urea cycle disorder shortly after birth. Because it is not possible to diagnose it in the womb in cases where there is no family history, the team aims to better counsel families contemplating pregnancy about their possible risks.

Research described in this post was underwritten by the NIH through its Rare Diseases Clinical Research Network.

preterm brain scans

Early lipids in micropreemies’ diets can boost brain growth

preterm brain scans

Segmentation of a preterm brain T2-weighted MRI image at 30 gestational weeks [green=cortical grey matter; blue=white matter; grey=deep grey matter; cyan=lateral ventricle; purple=cerebellum; orange=brainstem; red=hippocampus; yellow=cerebrospinal fluid].

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 research presented during the Pediatric 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 Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and 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 Centers for Disease Control and Prevention, about 1 in 10 U.S. 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 newborns 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.

Pediatric Academic Societies 2019 Annual Meeting presentation

  • “Early lipid intake improves brain growth in premature infants.”
    • Saturday, April 27, 2019, 1:15-2:30 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.