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Soy-based Formula Infants, Bone Strength Genetics, Infant Epilepsy, Intravenous Arginine, Concussion Conference

Published on March 23, 2018 in Cornerstone Blog · Last updated 6 months ago


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Along with the first day of spring (though the weather here doesn’t look quite like it just yet), the month of March marks National Nutrition Month — a great time to learn about how research is informing the impact of a healthy diet and lifestyle. This week’s roundup of Children’s Hospital of Philadelphia research headlines includes a recent study from the Division of Gastroenterology, Hepatology, and Nutrition at CHOP along with a handful of fascinating scientific discoveries that tell us new things about pediatric health across the lifespan (and across the skeleton, as you’ll see). Read on for summaries of the latest research from our investigators — from bone health to neurology to mitochondrial medicine and beyond.

Babies Fed Soy-based Formula Show Reproductive Tissue Changes

From concerns about allergies to difficulty feeding, mothers who don’t breastfeed sometimes use soy formula as an alternative to cow-milk formula. Soy protein, however, contains high amounts of plant-based, estrogen-like compounds that can interfere with a baby’s normal hormonal development. It’s critical to understand the effects of exposure to such compounds since the formula is the only source for many babies in the first six months of their life — a key developmental period — according to Virginia Stallings, MD, director of the Nutrition Center at CHOP.

In a new study funded and led by the National Institute of Environmental Health Sciences, Dr. Stallings and fellow researchers sought to learn more about how genistein, an estrogen-like compound found in soy-based formulas, influenced the development of estrogen-responsive tissues and hormone levels after birth.

“This was an observational study, not a randomized trial,” said Dr. Stallings in a press statement. “All of the mothers had decided on their feeding preferences before we enrolled them in the study.”

After comparing 102 infants exclusively fed with soy formula to 111 babies fed with cow-milk formula and 70 who were breastfed, the team found that babies who consumed soy-based formula as newborns had differences in some reproductive system cells and tissues. Though the differences pose no cause for alarm, they highlight a need to study the long-term effects of these estrogen-like compounds later into childhood and adolescence. The study appeared in the Journal of Clinical Endocrinology and Metabolism.

Learn more about the research in the press release.

Do Differences in Bone Strength Have Genetic Roots?

Leveraging “a different way to look at the skeleton” is one way that Jonathan Mitchell, PhD, a physician instructor in the Division of Gastroenterology, Hepatology, and Nutrition, describes a fascinating new study that analyzed discrepancies in bone density across the entire skeleton to uncover the genetic roots of bone strength. These genetic factors could potentially help physicians prevent osteoporosis.

The study, published in the Journal of Bone and Mineral Research, is the result of a collaboration between Mitchell and CHOP colleagues Struan F.A. Grant, PhD, co-director of the Center for Spatial and Functional Genomics, and Babette Zemel, PhD, director of the Bionutrition Core Laboratory. Together, the team dug into data from the Bone Mineral Density in Childhood Study, which measured bone mineral density in over 2,000 healthy 6-year-olds to 18-year-olds between 2002 and 2009. The large pediatric cohort contained bone data from sites all over a child’s skeleton.

Using a novel analytical approach, the researchers sorted out gene variants that were associated with both concordant skeletal measurements (bone densities that are consistent across the skeleton) and discordant measurements (where a patient has normal bone density in one part of the skeleton but low density in another). They found that most of the genetic variants for bone mineral density known to researchers are for concordant skeletal models — but interestingly, the team was also able to discover new genetic variants linked to discordant models.

“This study is a proof-of-principle for larger genomic efforts to further unveil genetic regulation of the pediatric skeleton,” Dr. Mitchell said. “Because a significant proportion of osteoporosis cases follow a discordant model, it’s important to better understand the underlying genetics and biology, with the aim of designing more precise treatments and preventive strategies.”

Learn more about the new study in the press release.

CHOP Researchers Discover Missing Mutation in Severe Infant Epilepsy

In a global collaboration with European and American researchers, CHOP investigators have identified a “missing mutation” in four unrelated children who suffered from severe infant epilepsy — the onset of which occurred within the first two weeks of their life. Like other children born with the condition, these patients suffered from severe to profound developmental delay, seizures that did not respond to medication, and lifelong disability.

In the Annals of Neurology, study leader Ethan Goldberg, MD, PhD, a pediatric neurologist at CHOP, and his co-authors described their discovery of long-suspected genetic changes in the children that may trigger overactive, brain-damaging electrical signals that lead to seizures. The team also found early evidence that suggests specific anti-seizure medications might prevent brain injury by controlling epilepsy during a key period after birth.

Though scientists already knew that the gene SCN3A had a pattern of high expression in the brain before and shortly after birth, and had previously linked variants in the gene to less severe forms of epilepsy, the current study solidified this link and also established that SCN31 mutations caused the severe infantile form of epilepsy.

“These are still early days, but we may be able to use this knowledge to protect the newborn brain and improve a child’s long-term outcome,” said Dr. Goldberg in a press statement.

Learn more about the science behind the study in the press release.

Intravenous Arginine Benefits Mitochondrial Patients Who Suffer Metabolic Stroke

Children with a wide range of mitochondrial disorders can suffer from metabolic strokes. Unlike classic strokes, metabolic strokes result from energy deficiency at the cellular level in brain regions that have a high energy demand. In a recent study published in Molecular Genetics and Metabolism, two CHOP experts in mitochondrial medicine reported on eight years of clinical experience providing arginine, an amino acid, intravenously to patients who suffered such stroke-like episodes and developed new-onset neurologic problems.

According to study leader Marni Falk, MD, executive director of the Mitochondrial Medicine frontier program, and co-author Rebecca Ganetzky, MD, clinical geneticist and attending physician in Mitochondrial Medicine, these children benefited from the rapid intravenous treatment and experienced no side effects from the treatment. In half of the stroke episodes, patients showed clinical improvements in symptoms like seizures and partial paralysis.

Though Dr. Falk said more research must be conducted — particularly in a larger group of patients — the analysis helps to support a budding evidence base of potentially promising treatments for a wide range of mitochondrial diseases. No prior studies have objectively evaluated intravenous arginine for mitochondrial disorders beyond one well-known syndrome, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS).

“Given these observed clinical benefits with low overall risks, our retrospective study data support the current use of IV arginine at the onset of acute metabolic strokes in children with many forms of mitochondrial disease,” Dr. Falk said. “As we move forward in mitochondrial medicine, we strongly encourage the objective evaluation of all current practices and potential therapies as rigorously as possible, both in preclinical models and in robust clinical trials.”

Read more about the study in the press release and learn about the Mitochondrial Medicine frontier program on Bench to Bedside.


Recently on Cornerstone, we met four remarkable women in science at the CHOP Research Institute to celebrate Women’s History Month and shared highlights from last week’s Lifespan Brain Institute mental health research symposium.

Catch up on our headlines from our March 9 edition of In the News:

  • Lung Stem Cell Offers Target for Regenerative Medicine
  • Philadelphia Hosts 2021 Congress of the International Society of Thrombosis and Haemostasis
  • Kristy Arbogast, PhD, Discusses Backseat Safety in the Washington Post
  • CHOP Cancer Experts Co-Author First Pediatric Pan-Cancer Analysis
  • CAR Research Assistant Awarded Gates Cambridge Scholarship

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