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Cardiovascular Medicine, Patient Care, Pediatrics, Pregnancy, Stanford News

World-first treatment for rare heart defect saves baby born at Packard Children’s

World-first treatment for rare heart defect saves baby born at Packard Children's

Group shot Liam and doctorsLinda Luna was five months pregnant with her first child when she got the bad news: Ultrasound scans showed a deadly defect in her baby boy’s heart. He had a 90 percent chance of dying before or just after birth. But thanks to a groundbreaking treatment at Lucile Packard Children’s Hospital Stanford, two-month-old baby Liam, who just went home to San Jose last week, is beating those odds.

He is the first baby in the world successfully treated with prenatal maternal hyper-oxygenation for his rare heart defect: congenital Ebstein’s anomaly. This week, several local news outlets report on the success of Liam’s case.

The problem at diagnosis? Due to severe leaks in two heart valves, blood flowed backward through the right half of Liam’s heart. His heart became dangerously enlarged. Too little blood reached his lungs and the rest of his body. Left untreated, the defect would cause irreparable heart and lung damage.

“Once you see type of leakage Liam had, it’s usually a progressive process,” said Theresa Tacy, MD, the fetal cardiology specialist who treated Liam in concert with his mom’s high-risk obstetrician, Katherine Bianco, MD, and a team of other specialists from across the hospital. “It just gets worse,” Tacy said. “The fetus eventually develops heart failure and dies.”

The team gave expectant mom Luna 12 hours per day of oxygen therapy for the last three weeks of her pregnancy. The idea was to relax Liam’s lung blood vessels with the extra oxygen he’d get from his mom. This would make it easier for his heart to pump blood forward into his lungs and, the doctors hoped, let him survive until birth and surgery.

Ebsteins vs normal by Tacy“We were trying to offer Liam’s parents hope but also remain realistic that their baby had a very high chance of not making it,” said cardiologist David Axelrod, MD, who cared for Liam in the cardiovascular intensive care unit after he was born. “We knew that even if he made it through pregnancy, his risk of dying during his first few days of life was very high.”

Immediately after his Nov. 22 birth, the doctors put Liam on an ECMO machine that delivered oxygen to his blood. Cardiothoracic surgeon Frank Hanley, MD, also closed a blood vessel near the heart to help Liam’s blood to flow forward. Finally, 11 days later, Liam was strong enough for a Dec. 3 surgery in which Hanley fully repaired his heart.

“It was a huge operation for a tiny baby fighting for his life,” Luna said. “The seven-hour wait during surgery was the longest wait of my life, but when they finally wheeled him out, he was a different baby. We were so thankful.”

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Genetics, Pediatrics, Precision health, Research

New cystic fibrosis screening test developed at Stanford

New cystic fibrosis screening test developed at Stanford

LungsStanford researchers have invented a new technique to detect cystic fibrosis in infants. The test, described in a paper published today in The Journal of Molecular Diagnostics, is more comprehensive, faster and cheaper than current newborn screening methods.

CF, which causes buildup of sticky mucus in the lungs and digestive organs, is the country’s most common fatal genetic disease. Newborn screening for the disease has been conducted in every U.S. state since 2010 and has mostly been a success story: Early diagnosis helps doctors start CF therapy more quickly, which can keep patients healthier longer. With good medical care, such as that provided by the CF experts at Lucile Packard Children’s Hospital Stanford, many people with CF now live into their 40s or beyond.

“Kids who are diagnosed early [with genetic screening tests] do not have a symptom-based diagnosis, so they don’t have to recover from any health insults,” study co-author Iris Schrijver, MD, told me when we discussed the research.

But there are limitations to the current screening tests. One big problem is that they can miss rare mutations in the CF gene, particularly those that prevail in nonwhite populations about whose CF changes scientists have limited knowledge. That’s especially an issue in California, where the 500,000 babies born each year have very diverse heritages. In fact, to help illuminate the problems of older CF tests, Schrijver recently published another study about the difficulty nonwhite CF patients face in receiving timely diagnosis.

In contrast to the current screening tests, the new test will detect virtually all CF-causing mutations in one step, which should make it far easier to find every affected newborn.

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Global Health, Health Policy, In the News, Pediatrics, Pregnancy, Women's Health

Ending preventable stillbirth: A Q&A with Stanford global-health expert Gary Darmstadt

Ending preventable stillbirth: A Q&A with Stanford global-health expert Gary Darmstadt

Today, prominent medical journal The Lancet publishes “Ending Preventable Stillbirth,” a series of articles calling for global efforts to greatly reduce fetal deaths that occur late in pregnancy or during labor. The series brings much-needed attention to a medical and societal problem that often goes ignored.

“Millions of women and families around the world have suffered the pain of stillbirth in silence,” said series adviser Gary Darmstadt, MD, a Stanford global-health expert who studies how to improve medical care for pregnant women, infants and children in developing countries.

Darmstadt recently answered my questions about why we should break the silence and work to lower stillbirth rates. “Many of the interventions that avert stillbirths also avert deaths of mothers and newborns,” he said. An edited version of his responses is below.

What’s the biggest misconception about stillbirth?

Perhaps the biggest misconception is that stillbirths don’t matter. There is a tradition of social stigma and lack of awareness of stillbirths that makes it easy to keep them out of sight and out of mind. But an estimated 1.2 million women around the world every year have an intrapartum stillbirth: They enter into labor after a normal pregnancy, with great expectations for a healthy baby and one of the most joyous experiences of a lifetime, only to face sudden devastation when the baby dies during birth. Their experiences matter.

A related misconception is that nothing much can be done to prevent stillbirth, or that prevention will divert scarce resources from other important issues. In fact, three fourths of intrapartum stillbirths around the world could be prevented through means that we take for granted in high income societies — such as skilled medical care before and during delivery — and that also benefit mothers, surviving newborns and children.

Why did the scientists involved in The Lancet’s new series think it was important to break the common pattern of silence, stigma and fatalism around stillbirth?

Stillbirth is a taboo topic in many societies, or worse yet, mothers are blamed for failing to deliver a healthy baby and feel intense social pressure to keep quiet about stillbirth. Their sense of loss and isolation may lead to depression, which in turn has many adverse consequences, including for subsequent pregnancies. On the other hand, many women who have the opportunity to talk about their experience with stillbirth and work through their grief express great relief and renewed hope. When the last Lancet stillbirth series came out five years ago, and women shared their experiences online or in parent support groups — often the first time they had ever shared their experience with stillbirth with anyone — many found this to be immensely healing and empowering. Thus, it was both the science showing the adverse effects of unexpressed and unresolved grief, and the testimonials of women who had experienced the benefits of breaking the silence that I believe influenced the scientists involved in The Lancet series to highlight this issue.

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Health and Fitness, In the News, Nutrition, Pediatrics

Teens need healthy brain food, says Stanford expert

Teens need healthy brain food, says Stanford expert

teens-healthy-foodToday, U.S. News and World Report released their 2016 ranking of the best diets. For their story on healthy eating for teenagers, Neville Golden, MD, division chief of adolescent medicine at Lucile Packard Children’s Hospital Stanford, explained how diet can affect teens’ brains and moods:

Teens are faced with myriad physical changes and academic demands, all while being bombarded by what their peers are doing – from what not to wear, to what to say and when to say it, to how to get the attention of you know who. And in the midst of all this, the body’s most critical organ – the brain –is still developing, says Dr. Neville Golden, a member of the American Academy of Pediatrics’ Committee on Nutrition…

“If [teens] don’t eat right, they can become irritable, depressed [and] develop problems such as obesity and eating disorders – and those have a whole host of psychological morbidities,” Golden says, adding that proper nutrition can help prevent and manage these conditions.

The rest of the story provides lots of specifics on how teens can improve their diets, including a sample menu for a day of healthy eating. If you know a teen who has made a nutritious New Year’s resolution, it’s definitely worth sharing.

Previously: Want teens to eat healthy? Make sure they get a good night’s sleep, Living near fast food restaurants influences California teens’ eating habits and British teens not getting enough fruits, veggies
Photo by Nestlé

Pregnancy, Research

New drug target for treating preterm labor identified in Stanford study

New drug target for treating preterm labor identified in Stanford study

pregnantbelly-4Here’s one of the biggest mysteries of pregnancy: How does the uterus muscle manage to stay quiet for most of gestation, yet shift to big, strong contractions when it’s time for the baby to be born?

The answer is not just a matter of scientific curiosity. Preterm birth recently surpassed infectious disease as the leading cause of death in kids under age 5 worldwide, and doctors urgently need better drugs to halt uterine contractions when a pregnant woman shows up at the hospital in early labor.

Current labor-slowing drugs delay but don’t entirely prevent preterm birth. They also can have bad side effects. Because they work by blocking voltage-gated calcium channels, which are a key widget in the mechanics of muscle contraction, high doses of these drugs have a detrimental effect on other muscles around the body, especially the heart.

So a Stanford team led by David Cornfield, MD, went back to the lab bench to learn more about the biology of uterine contractions. Today, they report in Science Translational Medicine on how their findings may yield a new way to stop early labor.

The researchers focused their work on a calcium channel that they suspected fine-tuned the action of the uterine muscle. They demonstrated that this channel, called the “transient receptor potential vanilloid 4 channel,” has effects that are specific to the uterus during pregnancy.

For instance, their data show greater expression of the Trpv4 gene and higher levels of the TRPV4 protein in the uterus of pregnant than non-pregnant rats. The levels fall off again after the rats give birth. Trpv4 gene expression levels were also higher in uterine tissue from pregnant than non-pregnant humans. In mouse experiments, the team also found that blocking the TRPV4 channel could reduce the ability of oxytocin, a labor-triggering hormone, to cause uterine contractions. In addition, a TRPV4-blocking chemical delayed birth in a mouse model of preterm labor.

The new findings strongly suggest that the TRPV4 calcium channel fine-tunes the sensitivity of the uterus, helping it shift from the quiet state that persists through most of pregnancy to the very strong contractions needed before birth. That means the channel could be a great target for new labor-stopping drugs. Cornfield and his colleagues are eager to continue their work to see if it can be used to develop a medication that’s safe for humans and will help more pregnancies continue all the way to term.

Previously: Stanford microbiome research offers new clues to the mystery of preterm birth, Stanford/VA study finds link between PTSD and premature birth and Maternal obesity linked to earliest premature births, says Stanford study
Photo by Teza Harinaivo Ramiandrisoa

 

Cardiovascular Medicine, Pediatrics, Transplants

Unusual bridge-to-transplant method helps teen get new heart and lungs

Unusual bridge-to-transplant method helps teen get new heart and lungs

bridge-to-transplant device
Earlier this year, Oswaldo Jimenez’s heart and lungs were failing. He needed a combined heart-lung transplant, but his doctors at Lucile Packard Children’s Hospital Stanford were worried that the 14-year-old from Salem, Oregon might not survive the wait for donor organs.

Stanford physicians have lots of experience with using external and implanted pumps that can support a patient’s failing heart. A few years ago, for instance, an 8-year-old patient spent 229 days with a Berlin Heart pump that moved blood through her body while she awaited a heart transplant.

Oswaldo’s case was different. Although his heart failure was significant, his failing lungs posed the biggest risk to his health. His doctors were concerned that his poor lung function would immobilize him – yet to benefit from transplanted lungs, he needed to stay fairly fit and mobile while he waited.

So the doctors decided to try an unusual bridge-to-transplant procedure called a “pulmonary to left atrial shunt,” which connected Oswaldo’s heart to a portable box outside his body that oxygenated his blood. Essentially, the team gave Oswaldo a temporary, artificial lung.

A press release from the hospital explains how it worked:

The procedure involved the insertion of a tube that redirected blood away from Oswaldo’s lungs into the oxygenator. This, in turn, provided oxygen to the blood and then returned it to his body, with his own heart providing the pump. Reports on this shunt device being able to sustain patients’ lives range from several weeks to six months, depending mostly on being able to prevent the blood from clotting while avoiding complications such as bleeding or stroke.

On July 12, Oswaldo made history by becoming the first child in the western United States to undergo this treatment — it saved his life and bought him time. Then, just one week after receiving the shunt, donor organs became available. Oswaldo received his heart and lung transplant on July 19.

Oswaldo is still recovering at the Ronald McDonald House, and his doctors think he’ll be able to go home close to the New Year. He’s looking forward to being a kid again, and his grateful family is thinking about how his case might benefit other kids in similar situations. “Now the doctors can use this therapy to treat other patients,” said Oswaldo’s mom, Carmen Hernandez.

Previously: Stem cell medicine for hearts? Yes please, says one amazing family, “Liberated from LVAD support”: One patient’s story and Image of the Week: First heart-lung transplant
Image of pulmonary to left atrial shunt courtesy of Lucile Packard Children’s Hospital Stanford

Behavioral Science, Mental Health, Pediatrics, Research, Stanford News

Stanford ingenuity + big data = new insight into the ADHD brain

Stanford ingenuity + big data = new insight into the ADHD brain

ask-the-brainAttention-focusing brain networks interact more weakly than usual in kids with attention deficit hyperactivity disorder, new Stanford research shows.

The research, published online today in Biological Psychiatry, is part of an ongoing effort to figure out how the brain differs from normal in people with ADHD. The disorder is both serious and common: It’s characterized by impulsiveness, hyperactivity and difficulty paying attention, and it has been diagnosed in more than 6 million U.S. children.

The new study focused on a particular set of linked brain regions called the salience network. From our press release:

“A lot of things may be happening in one’s environment, but only some grab our attention,” said Vinod Menon, PhD, a professor of psychiatry and behavioral sciences and the study’s senior author. “The salience network helps us stop daydreaming or thinking about something that happened yesterday so we can focus on the task at hand. We found that this network’s ability to regulate interactions with other brain systems is weaker in kids with ADHD.”

The research could lead to better diagnostics for ADHD, Menon said. That’s a big deal because, right now, diagnosis is based on subjective assessment of a child’s behaviors, and the threshold of behavior considered sufficient for diagnosis varies quite widely. Doctors worry about the risks of diagnosing ADHD in kids who don’t have it, or who actually suffer from a different psychiatric problem, and also about missing children who really should get a diagnosis.

But prior efforts to find an ADHD biomarker have been hampered by weak science. Many papers reporting brain-scan features of ADHD have not withstood attempts to replicate their findings.

The new study is different: Not only did Menon’s team find that their analysis could distinguish ADHD patients from controls with brain scans, it did so in three independent data sets. The data, from an open-source database of fMRI scans called the ADHD-200 Consortium, was collected using a different MRI scanner and slightly different clinical assessments at each site.

“We could use biomarkers developed from one site — New York — to classify ADHD children in another site, Beijing,” Menon said. The biomarkers also worked for the data from the third study site, which was Portland, Oregon. The fact that the findings held for all three sites gives an important level of real-world assurance that they’re meaningful.

More research is still needed to investigate whether brain scans can distinguish children with ADHD from those with other psychiatric conditions. But Menon thinks the work is on track to making a practical difference for better ADHD diagnostics.

Previously: A visual deluge may provide clues to ADHD treatment, Scientists reveal link between dopamine receptor subtype and ADHD diagnosis and Study finds many teachers, doctors mistaking immaturity for ADHD
Photo by Thomas Hawk

Genetics, Pain, Pediatrics, Precision health, Stanford News

Newly identified gene mutation explains why one family experiences unusual pain response to cold

Newly identified gene mutation explains why one family experiences unusual pain response to cold

snowy-handprintIf you’ve ever plunged your hand into a tub of ice water, you know about the overlap between cold and pain: that deep, biting ache makes you want to get your hand out of the water – fast. But while the protective value of that sensation is obvious, scientists have always been a bit mystified by how pain-sensing nerves register cold temperatures.

But now, research on a family with an extremely unusual gene mutation may help clarify what’s going on. The mutation, whose discovery was reported online this week in Nature, confers a heightened pain response to cold. The research was initiated by Stanford geneticists and expanded by scientists at three universities in Germany who specialize in hereditary pain syndromes.

The story began with a family who brought their young daughter to Lucile Packard Children’s Hospital Stanford to get help for her unusual episodes of pain. When cold, she experiences pain in her joints that radiates out to her arms and legs. The pain lasts 20 to 30 minutes at a time. The little girl’s father, paternal grandmother, paternal aunt and first cousin (the aunt’s daughter) also experience similar pain episodes, as the new paper explains in detail.

“When we saw her, we were really struck by the fact that the pain was going on in multiple generations of the family,” said one of the study’s authors, medical geneticist Jon Bernstein, MD, PhD. The pattern of inheritance made Bernstein suspect an autosomal dominant disease, in which only one bad copy of a gene causes symptoms. Although several hereditary pain syndromes are described in the medical literature, none matched the exact pattern of symptoms this family experienced, so the Stanford clinicians asked the German scientists to figure out what was going on.

The German team looked for rare mutations shared by the little girl and her cousin, finding one in a gene that codes for an electrical channel in nerve cell membranes. (Nerves transmit electrical signals via flow of charged ions through tiny protein tubes embedded in the cell membrane. There are several types of these channels.) The scientists’ experiments demonstrated that they had discovered a gain-of-function mutation – in which the encoded protein, instead of being rendered nonfunctional, instead alters what it does. In this case, there is a substitution of one amino acid for another in the structure of the affected electrical channel. That change causes pain-sensing nerves to fire at cool temperatures most people don’t find painful.

The same electrical channel, Nav1.9, was also identified as “a key determinant of cold pain sensation” in a paper published earlier this year that examined its activity in rats and mice. That study found that the channel was important to setting animals’ threshold for when cold begins to feel painful, and the new findings fit into that picture nicely.

The German team plans to continue studying the channel’s dynamics to help learn more about the normal threshold between cold and pain, Bernstein said. As for him? “I’m very much looking forward to working with the next family whose case is unsolved,” he told me.

Previously: One mutation, two people and two (or more) outcomes: What gives?, Crying without tears unlocks the mystery of a new genetic disease and Exploring the mystery of pain
Photo by Chris Geatch

Education, Nutrition, Public Health, Research, Stanford News, Videos

Online Stanford nutrition course improves participants’ eating habits, study finds

Online Stanford nutrition course improves participants' eating habits, study finds

I’m a big fan of Stanford’s free online course on child nutrition and cooking. And it’s not just me: Since the course launched in early 2014, more than 200,000 people have enrolled and watched the quick, informative, charming videos about understanding nutrition and making healthy food for kids. My favorite video, above, shows how to cook toad-in-a-hole, a comfort food I’ve loved since my own childhood.

Recently, instructor Maya Adam, MD, and her colleagues tested the effect of completing the course. When they designed the course, they hoped it would improve participants’ eating habits. A few other institutions had seen promising results from smaller online nutrition courses, but none of those combined nutrition instruction with hands-on demos of how to actually put their advice into practice in the kitchen. Yet other research suggests that making this connection between the “why” and “how” of healthy eating is important, since many people say that their lack of cooking know-how keeps them from eating well.

The results of the study, which appears in the International Journal of Behavioral Nutrition and Physical Activity, showed that the course is a success. Based on data from 7,422 participants surveyed about their eating habits before and after taking the course, the material presented helped participants cook fresh foods at home more often and eat more fresh fruits and vegetables. After the course, participants were also more likely to say that their previous day’s dinner was enjoyable and healthy.

“This is part of a growing body of research suggesting that just learning to cook can lead to improved dietary intake, which has amazing implications for public health interventions aimed at preventing overweight and obesity,” Adam told me in an e-mail.

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Ethics, In the News, Parenting, Patient Care, Pediatrics, Stanford News

Parents now help doctors decide what care is right for the sickest babies

Parents now help doctors decide what care is right for the sickest babies

Today, NPR’s Morning Edition featured an in-depth story on the evolution of decision-making in neonatal intensive care units – hospital nurseries for the sickest infants. Parents now have much more say in their babies’ care than in the past, and Stanford experts who were on the front lines of the change, including William Benitz, MD, chief of neonatology at Lucile Packard Children’s Hospital Stanford, explained how it happened.

As medical care for premature and other at-risk babies advanced in the 1970s and early 1980s, doctors gained the ability to save many infants who would once have died soon after birth. But some children in the new category of survivors had lifelong disabilities, with lasting implications for them and their families.

At first, doctors did not realize that this change would affect parents’ desire to participate in planning medical decisions for fragile infants:

“It never occurred to anyone that that might be a reasonable conversation to have,” Benitz says. “We were in unexplored territory.”

As technology improved and doctors tried to save sicker babies, and some born even earlier in gestation, there were new decisions to make: Should the health team put the tiny child on a ventilator? Attempt heart surgery? Those interventions helped many infants survive. Others did not fare as well.

“A lot of them ended up with significant impairments,” Benitz recalls. And doctors started to get pushback. “In the mid-80s we began to hear from families that maybe that wasn’t consistent with their goals for their children.”

As a result, neonatologists began having in-depth conversations with parents about the possible outcomes of different treatments for their infants. The practice is now widespread, and it means a lot to parents like Karin and Chris Belluomini, whose daughter, Joy, was born in May 2015 with Down syndrome, several heart defects and fluid around her lungs.

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