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

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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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).

Having a relative with type-1 diabetes makes you 15 times as likely as other people to get the disease, in which the body inappropriately destroys insulin-producing cells in the pancreas. But unlike the more common form of diabetes, type-2 diabetes, physicians don’t know how to prevent type 1 diabetes from developing in at-risk individuals.

To find out, they’re studying family members of type-1 diabetes patients. The large, multi-center research effort, called Type-1 Diabetes TrialNet, screens these folks for the presence of antibodies that recognize “self” tissues and could act as markers of diabetes vulnerability, and invites individuals who have the autoantibodies to take part in diabetes-prevention research. Stanford and Lucile Packard Children’s Hospital are among the 18 clinical centers participating in TrialNet research.

The big news at TrialNet is that, starting today, the first part of the screening process is moving online. Volunteers used to have to participate in a screening event or come to a trial center to be screened, but many people live far from these centers. At the TrialNet screening website, people can now answer a short set of questions to find out if they’re eligible for TrialNet’s research and give consent to participate in screening. After the online questions are complete, eligible volunteers will receive a kit in the mail that they can take to a local lab for a free screening blood test.

Researchers hope this online process will make it easier for more people to participate in type 1 diabetes research. TrialNet must screen more than 20,000 relatives of people with type 1 diabetes each year to reach its scientific goals, according to an National Institutes of Health press release about the new online screening.

Previously: Beta cell development explored by Stanford researchers, Researchers struggle to explain rise of Type 1 diabetes and A patient perspective on social media

Third grade is a critical year for learning arithmetic facts, but while math comes easily to some children, others struggle to master the basics.

Now, researchers at Stanford have new insight into what separates adept young math students from those who have difficulty. The difference, described in a paper published today in the Proceedings of the National Academy of Sciences, can’t be detected with traditional intelligence measures such as IQ tests. But it shows up clearly on brain scans, as the new study’s senior author explained in our press release:

“What was really surprising was that intrinsic brain measures can predict change — we can actually predict how much a child is going to learn during eight weeks of math tutoring based on measures of brain structure and connectivity,” said Vinod Menon, PhD, the study’s senior author and a professor of psychiatry and behavioral sciences.

Menon’s research team conducted structural and functional MRI brain scans before third-grade students received 8 weeks of individualized math tutoring. The tutoring followed a well-validated format, combining instruction on math concepts with practice of math problems emphasizing speed. All the children who received math tutoring improved their math performance, but the performance improvements varied a lot — from 8 percent to 198 percent.

A few specific brain characteristics were particularly good at predicting which kids would benefit most from tutoring. In particular, a larger and better-wired hippocampus predicted performance improvements. The brain structures highlighted in the study are implicated in forming memories, and differ from the portions of the brain that adults use when they are learning about math. The fact that these systems are involved helps to explain why the combination of conceptual explanations and sped-up practice that the study’s tutors used is effective, Menon explained:

“Memory resources provided by the hippocampal system create a scaffold for learning math in the developing brain,” Menon said. “Our findings suggest that, while conceptual knowledge about numbers is necessary for math learning, repeated, speeded practice and testing of simple number combinations is also needed to encode facts and encourage children’s reliance on retrieval — the most efficient strategy for answering simple arithmetic problems.” Once kids are able to pull up answers to basic arithmetic problems automatically from memory, their brains can tackle more complex problems.

Next, the researchers plan to examine how brain wiring changes over the course of tutoring. The new findings could also help educators understand the basis for math learning disabilities, and may even provide a foundation for figuring out what kind of instruction could help children overcome these problems.

Previously: New research tracks “math anxiety” in the brain and We’ve got your number: Exact spot in brain where numeral recognition takes place revealed
Photo by Canadian Pacific

Medicaid, the federal health-insurance program for low-income individuals, is set to undergo a big expansion in 2014 as part of the implementation of the Affordable Care Act. That expansion is good news for the children of low-income adults who will be newly eligible for health insurance, according to an opinion piece published online yesterday in JAMA Pediatrics.

Under the current system, Medicaid and SCHIP health insurance cover a much larger proportion of low-income children than adults, with the result that many insured children have uninsured parents. While insuring kids is important, it isn’t always enough, say the authors of the new piece, who are from Indiana University and Boston University.

“Children with uninsured parents are significantly less likely to receive recommended health services, even if they themselves are covered,” they write.

However, because of the U.S. Supreme Court’s 2012 decision on the Affordable Care Act, states get to choose whether or not to expand Medicaid. (The Supreme Court ruled that the ACA’s Medicaid-expansion mandate was coercive.) This is where the story gets really interesting. The piece describes states’ financial concerns about Medicaid expansion – essentially, that it will be expensive to add people to the Medicaid rolls – but then elaborates on some of the financial factors that states turning down Medicaid expansion may not be considering:

…[O]verall, the cost of the Medicaid expansion to states would be less than 1% of their local gross state product. Others have illustrated that, because uncompensated care reimbursements will decrease under the ACA and because some individuals will shift from Medicaid coverage to coverage through the private exchanges, many states might actuallywind up saving money by accepting the expansion. Medicaid can also have a stimulative effect on the economy, leading to increased employment and revenues, and, once again, can increase the potential for overall savings for many states.

Refusing the expansion will also come at a cost to clinicians, offices, and hospitals. Disproportionate hospital share payments will be trimmed by the ACA, reducing a source of income to hospitals. If many citizens are denied Medicaid, then it is likely that they will remain uninsured. Providers that continue to care for them will do so at a significant loss. Although many complain that Medicaid reimbursements are too low, they are still better than nothing. Such a complaint also ignores the fact that reimbursements for primary care services (even those provided by subspecialists) will go up significantly under the ACA, starting this year.

The authors hope that some or all of the states that have announced they will not expand Medicaid will eventually decide the expansion would be beneficial for their low-income citizens, including parents and children, and for their overall financial picture.

Previously: Stanford economist Victor Fuchs: Affordable Care Act “just a start”, Roundtable of doctors discuss Affordable Care Act and Analysis: The Supreme Court upholds the health reform act (really)

Near the end of a woman’s pregnancy, obstetricians use ultrasound to check that the baby is poised to be born head-first. Since breech vaginal deliveries (with the feet or rear end first) are risky for both mom and child, many physicians opt to schedule a c-section if the baby isn’t head-down at the end of pregnancy.

However, before they take that step, doctors can perform a procedure called an external cephalic version (or simply “version”) to try to turn the baby. To do this, they push on the mother’s pregnant abdomen while carefully monitoring the baby with ultrasound. In the past, women were not given anesthesia during this procedure, but recent research has shown that administering anesthesia can make versions more successful, perhaps because the medications help to relax the women’s abdominal muscles and allow the physician to use less pressure. Unsurprisingly, moms who receive pain relief are also happier with the process than those who don’t.

But there’s a wrinkle: Some physicians have worried about the additional expense of using anesthesia for versions, since the anesthesiologist’s time and the drugs used come with costs. Researchers from Stanford and Lucile Packard Children’s Hospital decided to address this conundrum by analyzing whether the additional cost of anesthesia was offset by the savings from enabling more vaginal deliveries and avoiding some cesareans.

In our press release, Brendan Carvalho, MD, the lead author of the new research, explained the findings:

“[O]ur work shows that it doesn’t add significant costs, and most likely reduces overall costs because more women can avoid cesareans.”

…

The study found that using anesthesia increased average success rates of version procedures from 38 percent to 60 percent. Because it led to fewer cesareans, use of anesthesia also decreased the total cost of delivery by an average of $276; the range of cost differences estimated by the model extended from a $720 savings to a $112 additional cost.

Looking at the question of cost-effectiveness in a different way, the success rates of versions had to be improved at least 11 percent with anesthesia for the cost of the anesthesia to be negated, the researchers calculated.

So far, Carvalho said, Packard Children’s is one of only a few Bay Area hospitals offering anesthesia for versions. But he hopes his team’s findings will encourage more physicians to consider the practice, since it’s good for both mothers’ well-being and hospitals’ bottom lines.

Previously: Should midwives take on risky deliveries?
Photo by Trevor Bair

Here’s a new reason to dislike smog: Air pollution from traffic has been linked to birth defects in a large new Stanford study of women who lived in California’s smoggy San Joaquin valley during the early weeks of their pregnancies.

From our press release on the study:

“We found an association between specific traffic-related air pollutants and neural tube defects, which are malformations of the brain and spine,” said the study’s lead author, Amy Padula, PhD, a postdoctoral scholar in pediatrics. The research appears online today in the American Journal of Epidemiology.

“Birth defects affect one in every 33 babies, and about two-thirds of these defects are due to unknown causes,” said the paper’s senior author, Gary Shaw, PhD, professor of neonatal and developmental medicine. “When these babies are born, they bring into a family’s life an amazing number of questions, many of which we can’t answer.”

The new research focused on five structural birth defects thought to be potentially affected by the mother’s environment during pregnancy, as well as seven pollutants measured during the EPA‘s federally mandated monitoring of air quality. The researchers compared more than 800 women who had a pregnancy affected by a birth defect between 1997 and 2006 to a similar number of women who had healthy babies during the same period. All of the women lived in the San Joaquin valley during their first eight weeks of pregnancy, and each gave the researcher her home address so that her pollution exposure could be estimated using data from nearby EPA air-quality monitoring stations.

The study is just the beginning of researchers’ efforts to understand the effects of traffic pollution on fetal development. Although a few prior studies have suggested a possible link, they have focused on different geographic regions, have produced conflicting results and have had various flaws in their methods. The new study is the first, for instance, to evaluate women’s pollution exposure in early pregnancy, when birth defects are likely to be developing, rather than at birth.

Much work is still needed in this area, the scientists say, including widening the scope of birth defects studied and examining the effects of combinations of pollutants. If future studies support the new findings, they could offer a route for preventing some devastating birth defects.

Previously: Better diet in pregnancy shown to protect against birth defects, NIH study supports screening pregnant women for toxoplasmosis and Federal government tests potential health risks of 10,000 chemicals using high-speed robot
Photo by Lynn Friedman

A large body of scientific research supports the safety and effectiveness of intrauterine devices and other forms of long-acting, reversible contraception (LARC) for adolescents, and physicians should offer these birth control methods to young women in their care. That’s the message behind a series of review articles published this week in a special supplemental issue of the Journal of Adolescent Health.

Stanford ob/gyn expert Paula Hillard, MD, who edited the supplement, explained to me that doctors are missing a great opportunity to prevent unwanted pregnancies by not offering young women the LARC birth control methods, which include IUDs and hormonal implants. Not only are the LARC methods very safe, the rate of unintended pregnancy with typical use of these techniques is 20 times lower than for alternate methods such as the Pill or a hormone patch.

But a design flaw in one specific IUD used in the 1970s – the Dalkon Shield – increased women’s risk for pelvic infections and gave all IUDs a bad rap. Use of IUDs among adult American women has been low ever since; it’s even lower in teens.

“Long after it was proven that the Dalkon Shield was particularly bad and newer IUDs were much safer, women were just scared,” Hillard said. “Not only did women stop asking for for them, many doctors also stopped using IUDs.”

The new review articles that Hillard edited are targeted at physicians but contain some interesting tidbits for general readers as well. The article titled “Myths and Misperceptions about Long Acting Reversible Contraception (LARC)” provides scientific evidence to refute several common myths, concluding, for instance, that IUDs don’t cause abortions or infertility, don’t increase women’s rates of ectopic pregnancy above the rates seen in the general population, and can be used by women and teens who have never had children.

And, as Hillard put it for me during our conversation, “These birth control methods are very safe and as effective as sterilization but completely reversible. They work better than anything else, and they’re so easy to use.”

Previously: Will more women begin opting for an IUD?, Promoting the use of IUDs in the developing world, and Study shows women may overestimate the effectiveness of common contraceptives
Photo, by ATIS547, shows a public sculpture on the campus of the University of California, Santa Cruz that is affectionately known as the “Flying IUD”

Food allergies affect millions of children, who find it difficult to enjoy ordinary activities like birthday parties and restaurant meals because of worries that something they eat could send them into anaphylactic shock. As the New York Times described recently, Stanford scientist Kari Nadeau, MD, PhD, is studying how to desensitize children to their allergy triggers. Here on Scope, she recently took questions on food allergies and her desensitization research.

Many readers asked how they could enroll in Nadeau’s research or in similar allergy treatment trials near their homes. Information for prospective study subjects around the world is available here; enter “food allergy” in the “Search for Studies” field, and after searching, click the “On a Map” tab to see trials grouped by location. For those who live near Stanford, go here for details on participating in Nadeau’s research.

Below are Nadeau’s responses to a selection of questions submitted using the hashtag #AskSUMed the comments section on Scope. As a reminder, Nadeau’s answers are meant to offer medical information, not medical advice. They’re not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and provide appropriate care.

@vikas_aditya asks: What’s the simplest way to identify the cause of an allergy in kids?

If you suspect an allergy to a specific food or environmental cause, skin prick testing is the simplest and least invasive way to initially identify the allergy but it is not the gold standard. A food challenge in the doctor’s office is the true way to test for food allergies.

Elizabeth P. asks: Is there anyone working to find the exact cause of why so many children, teens and adults are developing life-threatening food allergies today? On a related note, @ceband asks: What do you think of the theory that altered gut microbiomes have led to the rise in allergies and autoimmune disease?

Many scientists and researchers are trying to understand the rising prevalence of food allergies in children. Though there are many theories regarding the increase in this prevalence, we still lack definitive answers. Hypotheses have focused on hygiene, dietary fat, antioxidants, vitamin D and dual-allergen-exposure. Altered gut microbiomes might play a role. It does not appear that genetically modified foods are directly linked to food allergies.

Julie Barnes asks: I am currently pregnant and am wondering if I will possibly be creating a food allergy in my unborn child if I avoid all dairy and egg while pregnant and breastfeeding.

There is recent evidence that a diet in pregnancy and during breastfeeding that is high in Vitamin D, follows features of a Mediterranean diet and includes probiotics may be helpful to prevent asthma and allergies. And a healthy, balanced diet is important to your overall health and the health of your baby. However, we do not have evidence that mothers will create food allergies by food avoidance in pregnancy or breasfeeding. Similarly, there is no evidence from the general population that mothers can create food allergies by eating certain foods during pregnancy or breastfeeding.

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