Pediatrics

When babies are born with serious health problems, physicians’ main goal is to keep them alive. Thanks to decades of advances, such as support for preemies’ underdeveloped lungs and surgical procedures to correct complex birth defects, doctors can now save many babies who would once have died.

But some of these tiny survivors of high-risk birth still suffer permanent developmental problems. It’s only recently that physicians have begun to understand how to protect fragile infants’ developing brains.

As I describe in today’s issue of Inside Stanford Medicine, Lucile Packard Children’s Hospital recently became one of the first hospitals in the country to devote a section of its neonatal intensive care unit to specialized neurologic care for newborns. The new “Neuro NICU” will treat babies at risk for neurologic injury, including preemies, full-term infants deprived of oxygen during birth, and babies with congenital heart defects, who may receive too little oxygen in utero.

But knowing how to treat newborns’ brains is tricky because they change so fast, the story explains:

“The challenge and exciting thing about treating these tiny babies is that the brain is developing on a literally day-by-day basis,” said Courtney Wusthoff, MD, Packard Children’s neonatal neurologist.

Fortunately, new research findings and brain-monitoring technologies are helping doctors better understand infants’ immature nervous systems. For instance, they now have the tools to detect seizures that would once have gone undetected:

“In the past, it’s been assumed that you could just tell by looking if a newborn was having a seizure,” Wusthoff said. But it turns out that 80 to 90 percent of seizures in this age group cause no outward changes. “Newborns’ brains are not developed enough to show on the outside what’s happening on the inside.”

Wusthoff and her colleagues anticipate that the next several years will give doctors even better ways to understand and care for babies’ brains.

Previously: Increasing breast milk feeding rates for preemies at California hospitals , A look at the world’s smallest preterm babies and Advancing heart surgery for the most fragile babies
Photo of Jackson Thomas and Packard Children’s NICU nurse Diana Powell courtesy of the Thomas family

My lovely friend Maya Adam, MD, recently launched a free online course, “Child Nutrition and Cooking,” through Coursera, a web-based platform for “massive open online courses.”

In this fun, five-week “MOOC,” participants learn about the basics of child nutrition and how to make healthy meals for children and families. Weekly lectures are broken down into bite-sized, fact-filled video cooking tutorials, with homework assignments like “Prepare a colorful vegetable dish and send us a photo.” (Warning — your meal photos will be peer-reviewed, so presentation matters.)

For Adam, a lecturer on child health and nutrition in Stanford’s Program in Human Biology, developing this course was a labor of love. “My goal is to get people to return to a simpler, healthier and more economical way of cooking,” she recently told me. “By sharing a few tips and tools with family meal preparers, I hope to inspire a lifelong celebration of easy, home-cooked meals.”

So far, more than 22,000 aspiring cooks have signed up for the course, which just began its second week. Although the tutorials can be accessed at any time, by taking the course during this active period, participants benefit from live discussions with Adam, her teaching staff and fellow cooks.

Later in the year Adam will use these videos in her Stanford Human Biology courses through a “flipped-classroom” teaching model, which blends in-classroom and online lectures together to reinforce newly learned information.

Another caveat in taking this course: Don’t watch the cooking lessons on an empty stomach. Everything looks delicious, and it could lead to overeating.

Previously: Talking to kids about junk food ads, Sugar intake, diabetes and kids: Q&A with a pediatric obesity expert, New evidence for a direct sugar-to-diabetes link, Kids don’t need “kids’ food” and Smaller plates may be a tool to curtail childhood obesity
Photo courtesy of Stanford Online Learning

Today is the final day of our Ask Stanford Med installment on autism. Questions related to treatment, diagnosis and research advancements can be submitted to Carl Feinstein, MD, director of the Stanford Autism Center at Packard Children’s Hospital, by either sending a tweet that includes the hashtag #AskSUMed or posting your question in the comments section of our previous entry. We’ll accept questions until 5 p.m. Pacific time.

And, as a reminder, Feinstein and others will be speaking next month at a day-long event geared towards parents, teachers, physicians and caregivers. The sixth annual Autism Spectrum Disorders Update will be held at the Stanford campus on June 1.

Beyond providing a much needed escape for children battling cancer, video games can also be used to empower and educate them during chemotherapy and other therapies. As explained in a recent post on Observations, a team of medical researchers and software programmers at HopeLab created a collection of free, online games to help kids understand what’s happening inside their bodies during treatment, cope with unpleasant side effects and reinvigorate them so they have the strength to fight the disease.

HopeLab says that by playing the games, called Remission and Remission 2, pediatric cancer patients are more likely to adhere to their medication schedule, and the nonprofit recently partnered with Stanford researchers to study this potential benefit. Larry Greenemeier writes:

In the most recent study, HopeLab worked with Stanford University associate professor of psychology and neuroscience Brian Knutson on a functional magnetic resonance imaging (fMRI) study analyzing brain regions activated when people play the original Re-Mission. The paper, published in the March 2012 PLoS ONE, compared brain scans in 57 cancer-free undergraduates who were randomly assigned to actively play Re-Mission or passively watch the game. Re-Mission players experienced more activity in neural circuits associated with incentive motivation when compared to those who merely observed game play. Such reward-related activation could shift attitudes and emotions and boost players’ adherence to prescribed chemotherapy and antibiotic treatments to fight infection, the researchers said, although they acknowledge that further tests are needed on actual cancer patients before they can read too much into the results.

The above video describes the game and offers firsthand experiences from patients.

Previously: Improving patients’ lives through video games and Collaborative project creates a virtual world for cancer patients

Rotavirus, the most common cause of severe diarrhea among infants and young children, causes somewhere approaching a half million deaths annually, 100,000 of them in India and half of those among children less than a year old.

So the positive results announced today for a Phase III clinical trial of a rotavirus vaccine developed and manufactured in India are great news. The new vaccine cut cases of severe rotavirus-induced diarrhea by more than half – 56 percent – during the first year of life, with protection continuing into the second year of life. That compares favorably with the efficacy of the currently licensed rotavirus vaccines in low-income parts of the globe.

An Indian company, Bharat Biotech, sponsored the randomized, double-blind, placebo-controlled study and will soon file for registration of the vaccine in India.

The trial was conducted at three sites in India. About 6,800 infants who were between six and eight weeks old when they were enrolled received either the vaccine or a placebo in three doses spread over about two months, simultaneously with their routine immunizations for polio.

Stanford virologist Harry Greenberg, MD, a professor of medicine and of microbiology and immunology and the medical school’s senior associate dean for research, is a member of the senior scientific advisory group involved in all aspects of the vaccine’s development. Greenberg’s own past research was instrumental in producing the first-ever rotavirus vaccine, licensed in 1998. That vaccine was pulled off the market upon the discovery of a rare but life-threatening side effect called intussusception. But a study published in the New England Journal of Medicine in 2011 showed that intussusception risk is not only vastly outweighed by the benefits of vaccination, but may actually be at least as strongly associated with rotavirus infection itself as with the vaccine.

Two companies’ competing rotavirus vaccines are already licensed. But with one costing about $37 per two-dose course and the other going for about $50 per three-dose course, they’re prohibitively expensive for the vast majority of Indians. Bharat, the Indian biotech, has stated that it will sell this vaccine (its brand name is ROTAVAC) for a dollar a dose. At that price, assuming the product’s approval, it will save many, many thousands of lives every year.

Previously: Trials, and tribulations, of a rotavirus vaccine
Photo by QUOI Media

As part of efforts to promote exclusive breastfeeding, many hospitals are reducing their use of baby formula for newborns. But – as is being widely reported today – a new study published online in Pediatrics suggests that a strict no-formula approach in the early days of breastfeeding may sometimes amount to throwing the baby out with the bathwater.

The study focused on a problem that often derails moms’ early efforts to breastfeed: Early weight loss among newborns may prompt some mothers to switch from breastfeeding to formula-feeding because they worry that their babies aren’t getting enough to eat. Using a little bit of formula in a carefully controlled way may help these moms to stick with breastfeeding in the long run, the study found.

Here’s the back story: In the first three days after birth, instead of making milk, women produce small amounts of a fluid called colostrum. Colostrum is really good for babies, but there isn’t much of it, so it’s normal for babies to lose some weight before full-scale milk production begins. But if a baby loses more than five percent of his or her birth weight, doctors and moms can both get worried – especially if the mother’s milk is a bit slow to come in, or if the baby seems especially hungry or fussy.

Stanford/Packard Children’s pediatrician Janelle Aby, MD, who collaborated on the new study with a team of scientists at the University of California-San Francisco, told the San Francisco Chronicle:

In the first three days or so, the key complaint we hear is ‘I’m concerned I don’t have enough milk. I’m worried my baby is starving,’ ” said [Alby]. “Then we do daily weighs and it’s dropping and dropping, and that’s very stressful. Some moms, they get to a place where they can’t take it anymore and they give the baby formula.”

Yet giving formula at this point can derail breastfeeding completely – with a tummy full of formula, the baby may not be hungry enough to nurse. And using a bottle in the early days can cause “nipple confusion,” in which the baby finds the bottle easier to drink from and subsequently won’t take the breast.

The research team thought there might be a possible middle ground. They wondered if they could use just a little bit of judiciously delivered formula to help boost breastfeeding efforts. They taught mothers whose babies had lost at least five percent of their birth weight to supplement breastfeeding with small amounts of formula fed by syringe. The idea was to give hungry babies a little boost without feeding so much formula that they’d stop wanting to nurse. Using a syringe prevented nipple confusion. And once the moms’ milk came in, the formula supplements stopped.

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“Dylan’s Gift,” a documentary detailing how one family’s generosity is advancing research on a little-understood childhood cancer, has been nominated for an Emmy. The film, which was inspired by a 2009 Stanford Medicine story, explores the work of Stanford physician-scientist Michelle Monje, MD, PhD, who cares for pediatric brain cancer patients and conducts research on a rare, vicious brain tumor that arises in school-aged children and usually kills them within a year of diagnosis. As an FBR Media release explains:

When their 5-year-old son, Dylan, is diagnosed with a rare and fatal brain tumor and given just 6 months to live, Danah and John Jewett become determined to fight the deadly disease, called Diffuse Intrinsic Pontine Glioma (DIPG). When their son’s life is tragically cut short, they donate Dylan’s tumor to research at Stanford University School of Medicine. This generous gift has helped scientists create the first-ever mouse model of DIPG. The DIPG mouse model is now shedding light on this devastating disease and helping scientists discover new treatments and a potential cure to help other children. This episode was filmed on location at Stanford University School of Medicine.

In the above trailer, the Jewetts share their heart-wrenching story and discuss their decision to donate Dylan’s brain tumor after he passed away.

Previously: Documentary about childhood brain tumor research airs in San Francisco, Finding hope for rare pediatric brain tumor, Big advance against a vicious pediatric brain tumor, Video profiles work of pediatric brain tumor researcher and New Stanford trial targets rare brain tumor
Photo in the featured entry box courtesy of the Jewett family

Among school-aged children in the United States an estimated one in 50 has been diagnosed with autism spectrum disorder, according to a recent survey (.pdf) from the Centers for Disease Control and Prevention. In addition to raising concerns among researchers and parents about why the number of cases has increased, the findings underscored the need to do more autism research and to provide support and services for families caring for autistic children.

To help parents and others in the local community better understand the growing prevalence of autism and to learn about treatments and research advancements, the Stanford Autism Center at Packard Children’s Hospital will host its sixth annual Autism Spectrum Disorders Update on June 1. The event offers an opportunity for exchange between parents, caregivers and physicians and provides an overview of the center’s clinical services and ongoing autism research at the School of Medicine.

In anticipation of the day-long symposium, we’ve asked Carl Feinstein, MD, director of the center, to respond to your questions about issues related to autism spectrum disorder and to highlight how research is transforming therapies for the condition.

At the Stanford Autism Center, Feinstein works with a multidisciplinary team to develop treatments and strategies for autism spectrum disorders. In providing care and support for individuals with autism and their families, Feinstein and colleagues identify ways of targeting the primary autism symptoms, while also paying attention to associated behavior problems that may hold a child back from school or community involvement or seriously disrupt family life.

Questions can be submitted to Feinstein by either sending a tweet that includes the hashtag #AskSUMed or posting your question in the comments section below. We’ll collect questions until Wednesday (May 15) at 5 PM Pacific Time.

When submitting questions, please abide by the following ground rules:

• Stay on topic
• Be respectful to the person answering your questions
• Be respectful to one another in submitting questions
• Do not monopolize the conversation or post the same question repeatedly
• Kindly ignore disrespectful or off topic comments
• Know that Twitter handles and/or names may be used in the responses

Feinstein will respond to a selection of the questions submitted, but not all of them, in a future entry on Scope.

Finally – and you may have already guessed this – an answer to any question submitted as part of this feature is meant to offer medical information, not medical advice. These answers are not a basis for any action or inaction, and they’re also not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and give you the appropriate care.

Previously: New public brain-scan database opens autism research frontiers, New autism treatment shows promising results in pilot study, Autism’s effect on family income, Study shows gene mutation in brain cell channel may cause autism-like syndrome, New imaging analysis reveals distinct features of the autistic brain and Research on autism is moving in the right direction
Photo by Wellcome Images

Does it make a difference if a gene – or group of genes – is inherited from your mother or your father?

That’s the question behind the study of genomic imprinting, a phenomenon in which a small percent of genes are thought to be expressed differently depending on which parent they came from. In particular, animal research suggests imprinting may affect aspects of brain development. Researchers wonder if genomic imprinting might explain differences in brain anatomy seen between men and women, such as men’s larger brain volumes.

A new Stanford study, published today in the Journal of Neuroscience, adds to evidence that genomic imprinting is, in fact, happening in humans’ brains. The finding comes from MRI brain scans performed on a group of young girls with Turner syndrome, a chromosomal disorder in which a girl or woman has one missing or malfunctioning X chromosome. Turner syndrome gives an unusual opportunity to study genetic imprinting, because it allows comparisons of individuals who received a single X from Mom to those who got a single X from Dad. (The typical two-X-chromosome female body expresses a mosaic of Mom’s X and Dad’s X, making it impossible to tease apart the effects of the two parents. Males invariably get their single X chromosome from their mothers, so their cells always express the maternal X.)

The Stanford team, led by Allan Reiss, MD, documented several distinctions between the brains of Turner syndrome girls who have only a maternal X, those with only a paternal X, and typical girls with two X chromosomes, such as differences in the thickness and volume of the cortex, and in the surface area of the brain. The work helps clarify murky results from earlier studies of adults with Turner syndrome, the researchers say, because many adult women with Turner syndrome take estrogen supplements, which may have their own effects on brain development. None of the girls in the new study had taken estrogen.

The most tantalizing part of the paper is the scientists’ comment on the implications of their work for our general understanding of genetic imprinting. In part, they say:

By far, the most consistent finding with regard to sex differences in brain anatomy is the larger brain volume found in males compared with females. Although our groups did not differ on most whole-brain measures, our analyses revealed the existence of significant trends on total brain volume, gray matter volume and surface area, where these variables increased linearly from the Xp [paternal X] group being smallest, to the Xm [maternal X] group being largest, with typically developing girls in between. Considering that typically developing males invariably inherit the maternal X chromosome, while typically developing females inherit both and randomly express one of them in each cell, a linear increase in brain volume as seen in the present study is in agreement with what would be expected if imprinted genes located on the X chromosome were involved in brain size determination.

In other words, men may have their mothers to thank for their larger brains.

Karyotype image from a Turner Syndrome patient by S Suttur M, R Mysore S, Krishnamurthy B, B Nallur R – Indian J Hum Genet (2009).

Daily text messages may be an effective option to help children with asthma manage their symptoms and reduce doctor visits, according to recent research from the Georgia Institute of Technology.

In the study (.pdf), pediatric patients with asthma were randomly assigned to three programs: one group received text messages on alternate days, another received text messages daily and a third served as the control and did not receive any text messages. Participants ranged in age from 10 to 17 years old, owned a mobile phone and could read at the fifth grade level. The text messages asked patients questions about their symptoms and provided health information about asthma. Futurity reports:

Over four months, the intervention groups received and responded to SMS messages 87 percent of the time, and the average response time was within 22 minutes. After the study, the research team analyzed patients who had follow-up visits with their physician and found that sending at least one text message a day, whether it was a question about symptoms or about asthma in general, improved clinical outcomes.

“The results indicate that both awareness and knowledge are crucial to individuals engaging in proactive behavior to improve their condition,” [said Rosa Arriaga, PhD, who led the study].

The findings are noteworthy in light of past data showing texting is teenagers’ preferred method of communication, they get an average of 3,339 texts a month, and previous research showing they are amenable to receiving health information via text message.

Previously: CDC explores potential of using smartphones to collect public health data, Promoting healthy decisions among teens via text and Craving a cigarette but trying to quit? A supportive text message might help
Photo by Summer Skyes 11