This Special Music Helped Preemie Babies’ Brains Develop
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.
Couples Facing Fertility Treatments Should Beware of This
When Jane Stein and her husband used in-vitro fertilization in 2001 to become pregnant with twins, her fertility clinic recommended using a supplemental procedure called intracytoplasmic sperm injection (ICSI), known in fertility lingo as "ix-see."
'Add-on' fertility procedures are increasingly coming under scrutiny for having a high cost and low efficacy rate.
During IVF, an egg and sperm are placed in a petri dish together with the hope that a sperm will seek out and fertilize the egg. With ICSI, doctors inject sperm directly into the egg.
Stein, whose name has been changed to protect her privacy, agreed to try it. Her twins are now 16, but while 17 years have gone by since that procedure, the efficacy of ICSI is still unclear. In other words, while Stein succeeded in having children, it may not have been because of ICSI. It may simply have been because she did IVF.
The American Society for Reproductive Medicine has concluded, "There are no data to support the routine use of ICSI for non-male factor infertility." That is, ICSI can help couples have a baby when the issue is male infertility. But when it's not, the evidence of its effectiveness is lacking. And yet the procedure is being used more and more, even when male infertility is not the issue. Some 40 percent of fertility treatments in Europe, Asia and the Middle East now use ICSI, according to a world report released in 2016 by the International Committee for Monitoring Assisted Reproductive Technologies. In the Middle East, the figure is actually 100 percent, the report said.
ICSI is just one of many supplemental procedures, or 'add-ons,' increasingly coming under scrutiny for having a high cost and low efficacy rate. They cost anywhere from a couple of hundred dollars to several thousand – ICSI costs $2,000 to $3,000 -- hiking up the price of what is already a very costly endeavor. And many don't even work. Worse, some actually cause harm.
It's no surprise couples use them. They promise to increase the chance of conceiving. For patients who desperately want a child, money is no object. The Human Fertilization and Embryology Authority (HFEA) in the U.K. found that some 74 percent of patients who received fertility treatments over the last two years were given at least one type of add-on. Now, fertility associations in the U.S. and abroad have begun issuing guidance about which add-ons are worth the extra cost and which are not.
"Many IVF add-ons have little in the way of conclusive evidence supporting their role in successful IVF treatment," said Professor Geeta Nargund, medical director of CREATE Fertility and Lead Consultant for reproductive medicine at St George's Hospital, London.
The HFEA has actually rated these add-ons, indicating which procedures are effective and safe. Some treatments were rated 'red' because they were considered to have insufficient evidence to justify their use. These include assisted hatching, which uses acid or lasers to make a hole in the surrounding layer of proteins to help the embryo hatch; intrauterine culture, where a device is inserted into the womb to collect and incubate the embryo; and reproductive immunology, which suppresses the body's natural immunity so that it accepts the embryo.
"Fertility care is a highly competitive market. In a private system, offering add-ons may discern you from your neighboring clinic."
For some treatments, the HFEA found there is evidence that they don't just fail to work, but can even be harmful. These procedures include ICSI used when male infertility is not at issue, as well as a procedure called endometrial scratching, where the uterus is scratched, not unlike what would happen with a biopsy, to stimulate the local uterine immune system.
And then for some treatments, there is conflicting evidence, warranting further research. These include artificial egg activation by calcium ionophore, elective freezing in all cycles, embryo glue, time-lapse imaging and pre-implantation genetic testing for abnormal chromosomes on day 5.
"Currently, there is very little evidence to suggest that many of the add-ons could increase success rates," Nargund said. "Indeed, the HFEA's assessment of add-on treatments concluded that none of the add-ons could be given a 'green' rating, due to a lack of conclusive supporting research."
So why do fertility clinics offer them?
"Fertility care is a highly competitive market," said Professor Hans Evers, editor-in-chief of the journal Human Reproduction. "In a private system, offering add-ons may discern you from your neighboring clinic. The more competition, the more add-ons. Hopefully the more reputable institutions will only offer add-ons (for free) in the context of a randomized clinical trial."
The only way for infertile couples to know which work and which don't is the guidance released by professional organizations like the ASRM, and through government regulation in countries that have a public health care system.
The problem is, infertile couples will sometimes do anything to achieve a pregnancy.
"They will stand on their heads if this is advocated as helpful. Someone has to protect them," Evers said.
In the Netherlands, where Evers is based, the national health care system tries to make the best use of the limited resources it has, so it makes sure the procedures it's funding actually work, Evers said.
"We have calculated that to serve a population of 17 million, we need 13 IVF clinics, and we have 13," he said. "We as professionals discuss and try to agree on the value of newly proposed add-ons, and we will implement only those that are proven effective and safe."
Likewise, in the U.K., there's been a lot of squawking about speculative add-ons because the government, or National Health Service, pays for them. In the U.S., it's private insurers or patients' own cash.
"The [U.K.] government takes a very close look at what therapies they are offering and what the evidence is around offering the therapy," said Alan Penzias, who chairs the Practice Committee of the ASRM. It wants to make sure the treatments it is funding are at least worth the money.
ICSI is a case in point. Originally intended for male infertility, it's now being applied across the board because fertility clinics didn't want couples to pay $10,000 to $15,000 and wind up with no embryos.
"It is so disastrous to have no fertilization whatsoever, clinics started to make this bargain with their patients, saying, 'Well, listen, even though it's not indicated, what we would like to do is to take half of your eggs and do the ICSI procedure, and half we'll do conventional insemination just to make sure,'" he said. "It's a disaster if you have no embryos, and now you're out 10 to 12 thousand dollars, so for a small added fee, we can do the injection just to guard against that."
In the Netherlands, the national health care system tries to make the best use of its limited resources, so it makes sure the procedures it's funding actually work.
Clinics offer it where they see lower rates of fertilization, such as with older women or in cases where induced ovulation results in just two or three eggs instead of, say, 13. Unfortunately, ICSI may result in a higher fertilization rate, but it doesn't result in a higher live birth rate, according to a study last year in Human Reproduction, so couples wind up paying for a procedure that doesn't even result in a child.
Private insurers in the U.S. are keen to it. Penzia, who is also an associate professor of obstetrics, gynecology and reproductive biology at Harvard Medical School and works as a reproductive endocrinology and infertility specialist at Boston IVF, said Massachusetts requires that insurers cover infertility treatments. But when he submits claims for ICSI, for instance, insurers now want to see two sperm counts and proof that the man has seen a urologist.
"They want to make sure we're doing it for male factor (infertility)," he said. "That's not unreasonable, because the insurance company is taking the burden of this."
How exactly does your DNA make you who you are?
It's because of epigenetics that identical twins can actually look different and develop different diseases.
Just as software developers don't write apps out of ones and zeros, the interesting parts of the human genome aren't written merely in As, Ts, Cs and Gs. Yes, these are the fundamental letters that make up our DNA and encode the proteins that make our cells function, but the story doesn't end there.
Our cells possess amazing abilities, like eating invading bacteria or patching over a wound, and these abilities require the coordinated action of hundreds, if not thousands, of proteins. Epigenetics, the study of gene expression, examines how multiple genes work at once to make these biological processes happen.
It's because of epigenetics that identical twins – who possess identical DNA -- can actually look different and develop different diseases. Their environments may influence the expression of their genes in unique ways. For example, a research study in mice found that maternal exposure to a chemical called bisphenol A (BPA) resulted in drastic differences between genetically identical offspring. BPA exposure increased the likelihood that a certain gene was turned on, which led to the birth of yellow mice who were prone to obesity. Their genetically identical siblings who were not exposed to BPA were thinner and born with brown fur.
These three mice are genetically identical. Epigenetic differences, however, result in vastly different phenotypes.
(© 1994 Nature Publishing Group, Duhl, D.)
This famous mouse experiment is just one example of how epigenetics may transform medicine in the coming years. By studying the way genes are turned on and off, and maybe even making those changes ourselves, scientists are beginning to approach diseases like cancer in a completely new way.
With few exceptions, most of the 1 trillion cells that make up your body contain the same DNA instructions as all the others. How does each cell in your body know what it is and what it has to do? One of the answers appears to lie in epigenetic regulation. Just as everyone at a company may have access to all the same files on the office Dropbox, the accountants will put different files on their desktop than the lawyers do.
Our cells prioritize DNA sequences in the same way, even storing entire chromosomes that aren't needed along the wall of the nucleus, while keeping important pieces of DNA in the center, where it is most accessible to be read and used. One of the ways our cells prioritize certain DNA sequences is through methylation, a process that inactivates large regions of genes without editing the underlying "file" itself.
As we learn more about epigenetics, we gain more opportunities to develop therapeutics for a broad range of human conditions, from cancer to metabolic disorders. Though there have not been any clinical applications of epigenetics to immune or metabolic diseases yet, cancer is one of the leading areas, with promising initial successes.
One of the challenges of cancer treatments is that different patients may respond positively or negatively to the same treatment. With knowledge of epigenetics, however, doctors could conduct diagnostic tests to identify a patient's specific epigenetic profile and determine the best treatment for him or her. Already, commercial kits are available that help doctors screen glioma patients for an epigenetic biomarker called MGMT, because patients with this biomarker have shown high rates of success with certain kinds of treatments.
Other epigenetic advances go beyond personalized screening to treatments targeting the mechanism of disease. Some epigenetic drugs turn on genes that help suppress tumors, while others turn on genes that reveal the identity of tumor cells to the immune system, allowing it to attack cancerous cells.
Direct, targeted control of your epigenome could allow doctors to reprogram cancerous or aging cells.
The study of epigenetics has also been fundamental to the field of aging research. The older you get, the more methylation marks your DNA carries, and this has led to the distinction between biological aging, or the state of your cells, and chronological aging, or how old you actually are.
Just as our DNA can get miscopied and accumulate mutations, errors in DNA methylation can lead to so-called "epimutations". One of the big hypotheses in aging research today is that the accumulation of these random epimutations over time is responsible for what we perceive as aging.
Studies thus far have been correlative - looking at several hundred sites of epigenetic modifications in a person's cell, scientists can now roughly discern the age of that person. The next set of advances in the field will come from learning what these epigenetic changes individually do by themselves, and if certain methylations are correlated with cellular aging. General diagnostic terms like "aging" could be replaced with "abnormal methylation at these specific locations," which would also open the door to new therapeutic targets.
Direct, targeted control of your epigenome could allow doctors to reprogram cancerous or aging cells. While this type of genetic surgery is not feasible just yet, current research is bringing that possibility closer. The Cas9 protein of genome-editing CRISPR/Cas9 fame has been fused with epigenome modifying enzymes to target epigenetic modifications to specific DNA sequences.
A therapeutic of this type could theoretically undo a harmful DNA methylation, but would also be competing with the cell's native machinery responsible for controlling this process. One potential approach around this problem involves making beneficial synthetic changes to the epigenome that our cells do not have the capacity to undo.
Also fueling this frontier is a new approach to understanding disease itself. Scientists and doctors are now moving beyond the "one defective gene = one disease" paradigm. Because lots of diseases are caused by multiple genes going haywire, epigenetic therapies could hold the key to new types of treatments by targeting multiple defective genes at once.
Scientists are still discovering which epigenetic modifications are responsible for particular diseases, and engineers are building new tools for epigenome editing. Given the proliferation of work in these fields within the last 10 years, we may see epigenetic therapeutics emerging within the next couple of decades.