This Special Music Helped Preemie Babies’ Brains Develop
Listening to music helped preterm babies' brains develop, according to the results of a new Swiss study.
Move over, Baby Einstein: New research from Switzerland shows that listening to soothing music in the first weeks of life helps encourage brain development in preterm babies.
For the study, the scientists recruited a harpist and a new-age musician to compose three pieces of music.
The Lowdown
Children who are born prematurely, between 24 and 32 weeks of pregnancy, are far more likely to survive today than they used to be—but because their brains are less developed at birth, they're still at high risk for learning difficulties and emotional disorders later in life.
Researchers in Geneva thought that the unfamiliar and stressful noises in neonatal intensive care units might be partially responsible. After all, a hospital ward filled with alarms, other infants crying, and adults bustling in and out is far more disruptive than the quiet in-utero environment the babies are used to. They decided to test whether listening to pleasant music could have a positive, counterbalancing effect on the babies' brain development.
Led by Dr. Petra Hüppi at the University of Geneva, the scientists recruited Swiss harpist and new-age musician Andreas Vollenweider (who has collaborated with the likes of Carly Simon, Bryan Adams, and Bobby McFerrin). Vollenweider developed three pieces of music specifically for the NICU babies, which were played for them five times per week. Each track was used for specific purposes: To help the baby wake up; to stimulate a baby who was already awake; and to help the baby fall back asleep.
When they reached an age equivalent to a full-term baby, the infants underwent an MRI. The researchers focused on connections within the salience network, which determines how relevant information is, and then processes and acts on it—crucial components of healthy social behavior and emotional regulation. The neural networks of preemies who had listened to Vollenweider's pieces were stronger than preterm babies who had not received the intervention, and were instead much more similar to full-term babies.
Next Up
The first infants in the study are now 6 years old—the age when cognitive problems usually become diagnosable. Researchers plan to follow up with more cognitive and socio-emotional assessments, to determine whether the effects of the music intervention have lasted.
The first infants in the study are now 6 years old—the age when cognitive problems usually become diagnosable.
The scientists note in their paper that, while they saw strong results in the babies' primary auditory cortex and thalamus connections—suggesting that they had developed an ability to recognize and respond to familiar music—there was less reaction in the regions responsible for socioemotional processing. They hypothesize that more time spent listening to music during a NICU stay could improve those connections as well; but another study would be needed to know for sure.
Open Questions
Because this initial study had a fairly small sample size (only 20 preterm infants underwent the musical intervention, with another 19 studied as a control group), and they all listened to the same music for the same amount of time, it's still undetermined whether variations in the type and frequency of music would make a difference. Are Vollenweider's harps, bells, and punji the runaway favorite, or would other styles of music help, too? (Would "Baby Shark" help … or hurt?) There's also a chance that other types of repetitive sounds, like parents speaking or singing to their children, might have similar effects.
But the biggest question is still the one that the scientists plan to tackle next: Whether the intervention lasts as the children grow up. If it does, that's great news for any family with a preemie — and for the baby-sized headphone industry.
Drugs That Trick Older People’s Bodies to Behave Younger Might Boost the Effectiveness of a COVID-19 Vaccine
Because vaccination may be less effective in older people, it is imperative to test now whether immune boosters could help the efficacy of a COVID-19 vaccine in the elderly.
In our April 23rd editorial for this magazine, we argued that addressing the COVID-19 pandemic requires that we both fight the SARS-CoV-2 virus and fortify the human hosts who are most vulnerable to it.
Two recent phase 2 studies in older adults have suggested that a new category of drugs called rapalogues can in some cases increase the immunization capacity of older adults.
Because people over 70 account for more than 80 percent of reported COVID-19 deaths globally, this means we must do everything possible to protect our elders.
A range of recent studies have suggested that systemic knobs might metaphorically be turned to slow the cellular aging process, making us better able to fight off the many diseases correlated with aging. These types of systemic changes might be used to stem the specific decline in immunity caused by aging and to increases the biological capacity of elderly people to effectively fight viral infection.
But while helping make older people more resilient in the face of a viral infection is critical, that's not the only way geroscience can help in our fight against this deadly pandemic.
As we move toward hopefully developing one or more COVID-19 vaccines, researchers must more fully appreciate the ways in which traditional vaccines can be less effective in older people than in younger ones.
Repeated studies have shown that the flu vaccine, for example, has lower efficacy in older people than in younger ones. Older people tend to develop fewer antibodies after being vaccinated because a subset of their white blood cells, called T cells, have become less responsive over time. Some inflammatory peptides that increase with aging are also preventing the action of those T cells.
This is why there's a distinct possibility that a future COVD-19 vaccine, particularly one utilizing the traditional attenuated virus approach, could be less effective in older people than in younger ones.
Given the extreme urgency of developing vaccines that work well for everyone, we need to make sure that researchers are exploring all of the ways our elders can be best protected. While generating a vaccine that works equally well for people of all ages would be ideal, we can't count on that.
One way to bridge this gap might be to trick the bodies of older people into behaving as if they are younger just at the moment what a vaccine is delivered by giving them pre-immunization boosters.
Two recent phase 2 studies in older adults have suggested that a new category of drugs called rapalogues can in some cases increase the immunization capacity of older adults. Use of the drug for a short time period before flu shot immunization increased the antibody production for the flu and resulted in a 52 percent decrease in the occurrence of severe diseases needing medical help or hospitalization. This short-term pre-immunization intervention can also decrease the severity of serious respiratory tract infections, the deadliest manifestations of COVID-19, by similar magnitude. These patients also had almost half the incidence of the non-COVID-19 coronaviruses associated with the common cold.
The fact that those people were protected by treatment before hospitalization suggests metformin may have a role in boosting the vaccination of older people.
An inexpensive generic drug called metformin similarly targets the decline in immunity and inflammation (and extends health span and lifespan) in animals and has been used for decades to protect against the flu. A recent paper from a hospital in Wuhan, China showed that mortality of elderly COVID-19 diabetic patients on metformin was 25 percent less than that of patients with diabetes but not on metformin.
Another study from the U.S. showed that COVID-19 patients on metformin had a 20 percent decrease in mortality and lower inflammation. The fact that those people were protected by treatment before hospitalization suggests metformin may have a role in boosting the vaccination of older people.
We don't yet know whether rapalogues or metformin could be used as COVID-19 immunization boosters, not least because we don't have those vaccines. But we can and should make sure that all vaccine trials including older subjects also consider offering a subset of those subjects appropriate doses of rapalogues or metformin to explore whether doing so can boost the efficacy of a given vaccine.
If we weren't in the middle of the worst pandemic in a century, we would have more time to test our vaccines slowly and sequentially. In the context of the current crisis, however, testing whether immunization boosters might increase the efficacy of potential COVID-19 vaccines for older adults is at the very least a hypothesis worth exploring.
How We Can Return to Normal Life in the COVID-19 Era
A crowded baseball stadium is the epitome of "getting back to normal."
I was asked recently when life might return to normal. The question is simple but the answer is complex, with many knowns, lots of known unknowns, and some unknown unknowns. But I'll give it my best shot.
To get the fatality rate down to flu-like levels would require that we cut Covid-19 fatalities down by a factor of 5.
Since I'm human (and thus want my life back), I might be biased toward optimism.
Here's one way to think about it: Is there another infection that causes sickness and death at levels that we tolerate? The answer, of course, is 'yes': influenza.
According to the Centers for Disease Control, from 2010 to 2019, an average of 30 million Americans had the flu each year, leading to an annual average of 37,000 deaths. This works out to an infection-fatality rate, or IFR, of 0.12 percent. We've tolerated that level of illness death from influenza for a century.
Before going on, let's get one thing out of the way: Back in March, Covid-19 wasn't, as some maintained, "like the flu," and it still isn't. Since then, the U.S. has had 3.9 million confirmed Covid-19 cases and 140,000 deaths, for an IFR of 3.6 percent. Taking all the cases — including asymptomatic patients and those with minimal symptoms who were never tested for Covid-19 — into account, the real IFR is probably 0.6 percent, or roughly 5 times that of the flu.
Nonetheless, even a partly effective vaccine, combined with moderately effective medications, could bring Covid-19 numbers down to a tolerable, flu-like, threshold. It's a goal that seems within our reach.
Chronic mask-wearing and physical distancing are not my idea of normal, nor, I would venture to guess, would most other Americans consider these desirable states in which to live. We need both now to achieve some semblance of normalcy, but they're decidedly not normal life. My notion of normal: daily life with no or minimal mask wearing, open restaurants and bars, ballparks with fans, and theaters with audiences.
My projection for when we might get there: perhaps a year from now.
To get the fatality rate down to flu-like levels would require that we cut Covid-19 fatalities down by a factor of 5, via some combination of fewer symptomatic cases and a lower chance that a symptomatic patient will go on to die. How might that happen?
First, we have to make some impact on young people – getting them to follow the public health directives at higher rates than they are currently. The main reason we need to push younger people to stay safe is that they can spread Covid-19 to vulnerable people (those who are older, with underlying health problems). But, once the most vulnerable are protected (through the deployment of some combination of effective medications and a vaccine), the fact that some young people aren't acting safely – or maybe won't take a vaccine themselves – wouldn't cause so much concern. The key is whether the people at highest risk for bad outcomes are protected.
Then there's the vaccine. The first principle: We don't need a 100 percent-effective vaccine injected into 320 million deltoid muscles (in the U.S. alone). Thank God, since it's fanciful to believe that we can have a vaccine that's 100 percent effective, universally available by next summer, and that each and every American agrees to be vaccinated.
How are we doing in our vaccine journey? We've been having some banner days lately, with recent optimistic reports from several of the vaccine companies. In one report, the leading candidate vaccine, the one effort being led by Oxford University, led to both antibodies and a cellular immune response, a very helpful belt-and-suspenders approach that increases the probability of long-lasting immunity. This good news comes on the heels of the positive news regarding the American vaccine being made by Moderna earlier in July.
While every article about vaccines sounds the obligatory cautionary notes, to date we've checked every box on the path to a safe and effective vaccine. We might not get there, but most experts are now predicting an FDA-approvable vaccine (more than 50 percent effective with no show-stopping side effects) by early 2021.
It is true that we don't know how long immunity will last, but that can be a problem to solve later. In this area, time is our friend. If we can get to an effective vaccine that lasts for a year or two, over time we should be able to discover strategies (more vaccine boosters, new and better medications) to address the possibility of waning immunity.
All things considered, I'm going to put my nickel down on the following optimistic scenario: we'll have one, and likely several, vaccines that have been proven to be more than 50 percent effective and safe by January, 2021.
If only that were the finish line.
Once we vaccinate a large fraction of high-risk patients, having a moderate number of unvaccinated people running around won't pose as much threat.
The investments in manufacturing and distribution should pay off, but it's still inconceivable that we'll be able to get vaccines to 300 million people in three to six months. For the 2009 Swine Flu, we managed to vaccinate about 1 in 4 Americans over six months.
So we'll need to prioritize. First in line will likely be the 55 million Americans over 65, and the six to eight million patient-facing healthcare workers. (How to sort priorities among people under 65 with "chronic diseases" will be a toughie.) Vaccinating 80-100 million vulnerable people, plus clinicians, might be achievable by mid-21.
If we can protect vulnerable people with an effective vaccine (with the less vulnerable waiting their turn over a subsequent 6-12 month period), that may be enough to do the trick. (Of course, vulnerable people may also be least likely to develop immunity in response to a vaccine. That could be an Achilles' heel – time will tell.)
Why might that be enough? Once we vaccinate a large fraction of high-risk patients, having a moderate number of unvaccinated people running around won't pose as much threat. Since they're at lower risk, they have a lower chance of getting sick and dying than those who received the vaccine first.
We're likely to have better meds by then, too. Since March, we've discovered two moderately effective medications for Covid-19 — remdesivir and dexamethasone. It seems likely that we'll find others by next summer, perhaps even a treatment that prevents patients from getting ill in the first place. There are many such therapies, ranging from zinc to convalescent plasma, currently being studied.
Moreover, we know that hospitals that are not overrun with Covid-19 have lower mortality rates. If we've gotten a fairly effective vaccine into most high-risk people, the hospitals are unlikely to be overwhelmed – another factor that may help lower the mortality rate to flu-like levels.
All of these factors – vaccination of most vulnerable people, one or two additional effective medications, hospitals and ICU's that aren't overwhelmed – could easily combine to bring the toll of Covid-19 down to something that resembles that of the flu. Then, we should be able to return to normal life.
Whatever the reason, if enough people refuse the vaccine, all bets are off.
What do I worry about? There's the growing anti-vaxxer movement, for one. On top of that, it seems that many Americans worry that a vaccine discovered in record speed won't be safe, or that the FDA approval process will have been corrupted by political influences. Whatever the reason, if enough people refuse the vaccine, all bets are off.
Assuming only high-risk people do get vaccinated, there will still be cases of Covid-19, maybe even mini-outbreaks, well into 2021 and likely 2022. Obviously, that's not ideal, and we should hope for a vaccine that results in the complete eradication of Covid-19. But the point is that, even with flu-like levels of illness and death, we should still be able to achieve "normal."
Hope is not a strategy, as the saying goes. But it is hope, which is more than we've had for a while.