Where do we stand with understanding sudden unexplained infant deaths?

May 26, 2022  |  General  |  No Comments

There is no question that our understanding of sudden infant death syndrome (SIDS) has advanced significantly over the past couple of decades. But it still accounts for about 10 % of deaths in children under 1 year of age. The syndrome has also been renamed and its description broadened. It’s now generally called sudden unexplained infant death, or SUID. The current thinking is that SIDS is really a subset of SUID, although it is the largest subset. Trends in this are shown in the graph below, taken from this recent essay in the New England Journal of Medicine.

As you can see, the number of deaths from SIDS has been steadily dropping, being now only a third of what the number was in 1990. This has been attributed to the recognition that sleep position, particularly prone, influences the risk of SIDS. Hence the widely adopted “back to sleep” program of the American Academy of Pediatrics. But there are more complex things going on, and it’s clear we shouldn’t think of SIDS or SUID as only a problem of poor sleep hygiene. Modern medicine promotes a mixed, logically inconsistent message regarding SIDS: authoritative statements imply that SIDS is a consequence of unsafe sleep in biologically normal children, but there is vague acknowledgment that important biologic factors are involved in these deaths. What are these factors?

Observations from cardiorespiratory monitoring led to the association of serotonin and other neurotransmitter abnormalities in the brain stems of infants who died from SIDS with failures in autoresuscitation and arousal. Neuropathology associated with epilepsy has been observed in a substantial number of infants who died from SIDS. Numerous studies have revealed genetic differences between infants who died from SIDS and surviving, healthy infants; one study identified causative variants and plausible contributors to death in 11% of cases. Research on heritability in the back to sleep era revealed that younger siblings of babies who had died from SIDS were four times as likely as other babies to also die from SIDS; moreover, the risk of SIDS among first- through third-degree relatives was nine times as high as the risk in nonaffected families. So there’s a lot more going on here than sleep hygiene.

And another thing. After an infant dies from SIDS, often no standard medical care is provided to the family. Along with often failing to respond to families’ emotional pain and confusion, we permit postmortem assessment to focus primarily on the legalistic question of manner of death, rather than on the medical question of biologic and environmental causes. The current approach may answer questions about mistreatment, but it leaves any effort to know more about etiologic factors, including possible risks to siblings, to bereaved family members. Medicine doesn’t exhaustively attempt to explain these deaths, even though doing so would be routine in other disease areas.

So although it’s gratifying that the rate of SUID as decreased over the past decades, we appear to have reached a plateau. It is time of focus on molecular and physiologic mechanisms that might help explain the deaths that still occur. It’s probably complicated, but our capabilities now are far more sophisticated than when prone positioning was first shown to be a risk factor.

More disturbing data on the emergence of firearms as a leading cause of death in children

April 25, 2022  |  General  |  No Comments

I’ve written before how firearms injuries have emerged as a leading cause of traumatic death in children. A new study in the New England Journal of Medicine, as well as a good letter to the editor, examines this issue further. Note this is a difficult subject to study because Republican-controlled Congresses have legislated against even examining the question; it is truly an astonishing thing to try to prevent unfettered scientific study of a particular topic, presumably largely owing to lobbying efforts by the firearms industry and the NRA. Perhaps the recent civil settlement against the Remington company over the Sandy Hook mass shootings may allow change in this. We can only hope for now that it does.

As I described in my previous post, by 2016 firearms injury had risen to account for 15% of pediatric traumatic deaths, second only to motor vehicle accidents. These new data offer more insight into this disturbing trend. The graph below from the article displays the causes of pediatric deaths over the past two decades. It shows a couple of things. First, and most gratifying, it demonstrates a 50% drop in deaths from MVAs in children over the past 20 years. In the same period, however, there has been a 50% increase in pediatric deaths from firearms. The result is that gunshot deaths in children now exceed those from MVAs.

The reasons for this reduction in MVAs are instructive:

Two decades ago, the CDC proclaimed the reduction in deaths attributable to motor vehicle crashes to be one of the most substantial public health achievements of the 20th century. Most important, the United States established an infrastructure permitting continuous improvements in motor vehicle safety. At the forefront of this effort has been the National Highway Traffic Safety Administration (NHTSA), a federal agency whose mission is to save lives and prevent injuries caused by road-traffic crashes. Firearms, however, are one of the few products whose safety isn’t regulated by a designated federal agency.

The point is that a dedicated approach to improving product safety, plus active measures to reduce the rate of injuries, can have have very large effects. The first step is to develop dedicated data systems to collect information, and articles like this are helpful first steps. But these are relatively crude measures; we need specific breakdowns regarding the particulars — trends, disparities, and associations — of firearm injuries. The example of automotive safety is again instructive:

To support automotive safety, the NHTSA and the nonprofit Insurance Institute for Highway Safety provide vehicle safety ratings using crash-test results and fatality data. Motor vehicle companies, which for decades resisted competing on the basis of safety, reversed course and now often advertise their vehicles’ safety features.

In spite of rising death rates from firearms, many states have actually made it easier to gain access to firearms, particularly for adolescents. It has been shown that states with looser regulation of firearms have higher rates of deaths from them. This should not surprise anybody, certainly not me. But there remains pervasive denial of this common sense and now established correlation. The authors’ conclusion is straightforward — starting with gathering more scientific data on the question.

As the progress made in reducing deaths from motor vehicle crashes shows, we don’t have to accept the high rate of firearm-related deaths among U.S. children and adolescents. Preventable deaths among young people not only are associated with tremendous medical costs, but take a great personal toll on families and communities. To reverse the trend of increasing firearm-related deaths among U.S. children, experts and policymakers should be intentional in their efforts to develop and implement a multipronged scientific strategy centered on continuous improvement.

Bad news: Poverty affects children’s brains. Good news: Public policy can have a major beneficial impact on reducing these effects

April 10, 2022  |  General  |  No Comments

This has actually been known for some time, but recent evidence is compelling. A recent study from Harvard University suggests public policies aiming to reduce the harms of poverty may lead to larger brains in children. Scientists say that underscores the need for a strong social safety net. Researchers looked at brain images from 11,000 children in 17 different states that offered a range of health benefits and cash assistance to low income families. On average, they found children in states with generous benefits had a larger hippocampus, the section of the brain involved in learning, memory and emotion processing. They also had fewer mental health and behavioral problems. Harvard psychologist Kate McLaughlin said scientists have long found an association between poverty and brain size.

The question we had is whether the magnitude of that association — so how much [connection] growing up in a family that’s living in poverty has on a child’s brain development varies based on where you live.

The research team found almost a 40% difference in brain size among low-income children living in states with the most generous benefits, such as California, versus the least generous, like Oklahoma. That was after accounting for cost of living. They noted there could be other explanations. For instance, states with generous benefits may also invest more in education, and perhaps that impacts brain development. But they tried to control for most factors. Of course many policy makers try to hand wave this sort of finding away. One of the authors answers:

Well, you know, [some say] that could just be the individual family not using the right discipline strategies. In my experience, people have a harder time pretending that these associations aren’t meaningful and important when you show them that they’re having an impact at a biological level on how children’s brains are developing.

We now realize that a child’s brain is continuing to develop to at least age 18 and probably beyond. It’s self-evident to me a child’s surroundings, and in particular including diet, affects how the developing brain ends up. The stress of being poor, of not knowing where your next meal is coming from, activates hormone pathways in the body which arose through evolution as “fight or flight” responses to save you from an attacking wild animal. When they are activated chronically, bad things happen in the body.

It’s long past time we as a society do more to fix this.

Closing the Gender Pay Gap in Medicine

April 4, 2022  |  General  |  No Comments

A recent editorial in The New England Journal of Medicine highlighted something that really has been a running sore in medicine from many decades: the fact women physicians are paid on average about 75% of what men are paid for doing the same work. Our gender pay gap is actually one of the worst in any industry. There are some hoary, old, handwaving justifications for this. The usual suspects are that women often go to part-time to have and raise a family and that women tend to select specialties, such as my own of pediatrics, that rank among the lowest-paying specialties. The big bucks are to be found in procedural specialties, but also radiology and ophthalmology (even if not doing eye surgery). Yet research shows even when adjusting for confounders like this, a women physician is still paid less for doing the exact same thing as a man. The editorial discusses the many reasons for this. Left undiscussed, perhaps it’s kind of a third rail in this issue, is plain, old-fashioned misogyny. This does play some role now, and certainly did in the past. My own physician father, although excellent in many ways, used to make disparaging comments about “hen medics.” But he was a product of his times — 1940s through 1970s — and if he were alive now I hope his attitudes would be different.

One issue is the tendency of many women not to be hard-nosed negotiators. This is lose/lose for them. A man who does that is often expected, even applauded for it; a women can actually be downgraded for it.

Women are subject to a likability standard that men exhibiting similar behaviors are not. The prevailing cultural narrative that women are less skilled negotiators than men is too simplistic and contradicts decades of experimental research. In fact, women do negotiate, but when they do, they tend to be viewed as less hireable. 

Other stereotypes, pervasive throughout the workplace in many industries, show themselves in medicine, too:

Long-standing cultural expectations regarding women’s behavior remain at odds with well-accepted traits of leaders and high performers, even though organizations with female leaders often outperform those with male leaders. Women in the workplace are expected to be both directive and participative, decisive and caring, and executive and approachable, and they face backlash when their behavior violates these stereotypes. 

If you asked any department chair if he (overwhelmingly he) believes in equal pay for equal work, I am certain he would say “of course,” and possibly even resent you asking the question. Yet there are subtle and not so subtle ways inequality develops. One is women physicians tend to be shut out of the pipeline that leads to leadership, and thus higher paying positions. With many fewer women in leadership positions, there is a lack of role models for young women physicians. Now I have certainly seen male physicians who are exemplary mentors for women, but there is no question it would help if we had more women in leadership positions, especially in specialties traditionally dominated by men, such as all types of surgery.

Interestingly, there is a substantial literature showing women physicians, when compared nose to nose with male counterparts, actually provide better care — more thorough with better outcomes. Part of this is research shows women physicians tend to spend more time with patients. It’s not surprising outcomes are better. But of course in a pay scale system based, as many are, on “productivity,” or how many patients you see, women’s income suffers from spending more time on each patient. The authors summarize this way:

To close the pay gap in medicine, institutional leaders and their colleagues in human resources and finance will need to scrutinize basic assumptions underlying compensation methods to understand the expectations and outcomes they generate, create new approaches that better account for women’s traditional contributions and related biases, and track and report gender metrics at all compensation touch points, especially in initial hiring.

Half of all medical students are now women, a gratifying evolution from my father’s era, when only 5-8% were. Our profession needs to deal with this inequality now. It’s gone on far too long.

Identifying and treating eating disorders in children

March 30, 2022  |  General  |  No Comments

Eating disorders can be complex and hard to identify and treat in children and teens, but the earlier an eating disorder is detected, the better chance at a healthy outcome for a child. The American Academy of Pediatrics has published an excellent review of them here. It’s written for physicians but easily understandable for parents. For too long eating disorders were considered a disease that afflicted mostly affluent white teenage girls. We know today girls and boys of all ages, income levels, and racial and ethnic groups may be struggling with eating disorders.

Some adolescents may have dietary habits that disguise eating disorders, such as those who become increasingly restrictive about the quality—as opposed to the quantity​—​of their food consumption. Teens may spend excessive amounts of time in meal planning and experience extreme guilt or frustration when their food-related practices are interrupted. The average age for the onset of eating disorders is 12.5, but many have their onset later in adolescence. Common forms of them are anorexia nervosa, avoidant/restrictive food intake disorder, binge eating disorder, and bulimia.

If you are concerned your child may have an eating disorder, definitely consult your physician, but the link to the article above is full of useful information.

Needle-free epinephrine products could be available next year

Needle-free epinephrine products could be available next year

March 25, 2022  |  General  |  No Comments

Here’s some good news for parents with children with severe allergies, such as to peanuts or bee stings. If you are in that category you probably have to carry around with you an EpiPen, which is an autoinjector device for giving immediate epinephrine if your child is experiencing a severe allergic reaction. These things are life saving, but they do involve a needle and many people are squeamish or afraid of needles. Several companies presented posters on their needle-free epinephrine products at the recent American Academy of Allergy, Asthma & Immunology annual meeting. These included both an intranasal spray and a tablet to put under the tongue. Both approaches gave results, in terms of blood levels of the drug, as fast as the EpiPen autoinjectors. And speed to good blood levels is the most important thing in treating acute allergic reactions.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them, even though epinephrine itself is very safe. They can be afraid to use them and they don’t want to inject their child with a needle. So they hesitate at a time when minutes matter.

No word from the developers on the crucial question of cost or precisely when these products will be approved and available — the goal is for next year. There was a huge scandal several years ago when the maker of EpiPens jacked the price up by several hundred percent. This is pretty important, since families with a child who might need them generally have to have several — say one for the car, one for the purse, etc. Since in general injectable medications are much more expensive than pills or nasal sprays just from a manufacturing standpoint, one would hope that these needle-free products will also be cheaper.

COVID-19 appears to increase the risk of new diagnosis of type 1 diabetes in children

February 22, 2022  |  General  |  No Comments

When a child with new onset of type 1 diabetes appears in our health care network they are referred to the PICU for initial management. This is because they typically are extremely ill with what is called diabetic ketoacidosis, in which acid and other toxic materials caused by lack of insulin accumulate in the blood stream. Type 1 diabetes is the most common of what we term autoimmune diseases, in which the body’s immune system attacks itself. In this case, the autoantibodies attack the cells in the pancreas that make insulin and destroy them. We don’t know what causes this process, but most experts think it begins with a viral infection, after which the immune system, activated by the infection, turns rogue and attacks the insulin-producing cells. The propensity to do this is likely determined by a genetic predisposition.

Many of us have had the feeling we are seeing a spike in new cases of type 1 diabetes in children, and have wondered if the COVID-19 epidemic has anything to do with this increase. After all, an epidemic of a viral infection might be expected to increase the risk in genetically susceptible children. A recent study from the CDC’s respected Morbidity and Mortality Weekly Report gives us some new information about this. The authors looked at new cases of type 1 diabetes in children for the several years prior to the COVID epidemic to establish a baseline. They then evaluated new cases during the COVID epidemic and looked for differences between children who had COVID and those who didn’t. In a nutshell, the study documents an increased risk of type 1 diabetes in children following COVID-19 infection. Persons aged <18 years with COVID-19 were more likely to receive a new diabetes diagnosis >30 days after infection than were those without COVID-19. They also evaluated in parallel the effects of non-COVID respiratory infections; non-COVID-19 respiratory infection was not associated with an increased risk for diabetes. What was the size of this effect? The hazard ratio for developing type 1 diabetes in children with a documented COVID infection was quite significant for these sorts of studies — 2.66. This is not an isolated study. For example, a study from the UK estimated an 80% increase in their region of new cases of type 1 diabetes in children owing to COVID-19.

These are preliminary data and I’m further studies will follow. But this is yet another reason to vaccinate your children for COVID-19.

Some unintended health consequences of the COVID pandemic for children

December 26, 2021  |  General  |  No Comments

There have been some interesting downstream effects of the COVID pandemic on children’s health. For one, our annual influx of kids with RSV (respiratory syncytial virus) and influenza pretty much disappeared. Even the most common reason for young children to visit the doctor — ear infections (otitis media) — also was greatly reduced. My colleagues in primary care told me they went from several a day to one per month. This is quite understandable. Otitis media is essentially a complication of a a viral upper respiratory infection, a cold. With all the kids out of school and daycare closed, the usual ways children get viral infections were shut down. As an aside, now that these things are open again we’re seeing a wave of RSV, as expected. In my own PICU admissions were also down last winter, and this experience was shared by my colleagues. A recent study documented the dramatic drop in PICU admissions around the country.

PICU admissions overall were down by nearly 50% across the country. The most interesting thing was that, as expected during quarantine, admissions for respiratory critical illness were dramatically down. On the other hand, as you might also have expected, PICU admissions for poisoning, drug ingestion, suicide attempt, and endocrine issues, particularly diabetic ketoacidosis, were up. If you coop up all those kids some bad things can happen. This is shown in the graph below. It shows a moving 7-d average of daily PICU admissions during the baseline (averaged over 2017–2019) and 2020 study periods. Stay-at-home orders were initiated at all sites by March 24, 2020.

So maybe that’s good? But also, the pandemic quarantine led to a drop in essential preventative care measures in children. The most recent newsletter of the American Academy of Pediatrics raised the concern for a particular example of this — vision screening. Amblyopia is a disease of vision development affecting 3% of all children. It is highly treatable in the first years of life, but after about age 7 it becomes increasingly difficult to correct. Traditionally, screening for this condition has been part of well child visits, which were dramatically reduced with the quarantine. And it’s something that really needs to be done in person, not remotely or online. There are other examples. Only time will tell if there are other untoward effects of the lapse in well child visits. The authors of the PICU study’s conclusions are kind of glass half full, but do make an important point:

The physical distancing measures put in place to decrease transmission of SARS-CoV-2 were associated with widespread and substantial reductions in PICU admissions, suggesting that a considerable portion of pediatric critical illness may be preventable, particularly those due to respiratory and infectious illnesses. These findings may have important implications for child health and public policy. Further study is warranted to identify which strategies most effectively decrease transmission of childhood infections while avoiding the negative consequences of social isolation.

Poor children have less easy access to pediatric critical care services, and this matters

December 19, 2021  |  General  |  No Comments

It’s long been known poverty among children is highly associated with poorer overall health outcomes. A similar thing occurs in adults, but in children the effects are particularly striking. A recent study in Pediatric Critical Care Medicine highlights a new aspect of this issue — distance from a PICU. The authors examined the relationship between neighborhood socioeconomic status, race, and distance to PICUs throughout the United States. Using a data set with fairly precise neighborhood granularity, they explored this phenomenon nationally and within urban and rural cohorts. The data set they used is called the Area Deprivation Index, which is derived from 17 measures of education, employment, housing, and poverty. In this composite measure, the most advantaged neighborhoods return ADI’s of 1 and the most deprived neighborhoods return ADI’s of 10. The specific question they tried to answer was if children living in areas of higher ADIs were located further away from a PICU than children in more affluent areas. This is important because it’s known transport time matters in outcomes, as does the need to transfer a child from a hospital without a PICU to one with a PICU.

The results are quite interesting — and quite striking to me:

As you can see, there is a consistent linear relationship between ADI and distance to a PICU, from 15 miles in the more affluent places to 40-50 miles in poorer neighborhoods; the distance to pediatric critical care services decreases with affluence throughout the United States. Unlike adult critical care services, where a similar relationship is driven mainly by rural versus urban residential patterns, this was true in pediatrics across urban/suburban and rural regions. This phenomenon is fueled by the physical concentration of pediatric critical care services and by the growing number of suburban poor.

These observations carry implications well beyond the care of pediatric critical illness; it also impacts more ordinary pediatric care. In the United States, pediatric hospital care has become increasingly regionalized, with even very common medical conditions, such as abdominal pain and uncomplicated seizures, now being much more likely to be referred to specialized centers. I have seen this steady development over my own 40 plus years of PICU practice, and have written about it in the past here. Since a reasonable marker of these referral centers is the presence of a PICU, distance to the nearest PICU is also a measure of distance to solutions for a wide range of pediatric medical problems. Distance matters. As the authors conclude:

In summary, we have observed a strongly linear relationship between neighborhood affluence and distance to pediatric critical care services. As a result, children in the least affluent communities need to travel nearly three times as far to reach intensive care as those in the most affluent. This carries important implications for healthcare access and may contribute to income-related disparities in some pediatric health outcomes.

What is the latest on what is best for recurrent acute ear infections (otitis media): frequent antibiotics or ear tubes?

November 29, 2021  |  General  |  No Comments

This has been a controversial topic in pediatrics for many decades. In my forty year experience one of the most common determining factors in whether or not a child gets tympanostomy tubes (ear tubes) is whether or not they’ve been seen by an ENT physician (ear, nose, and throat surgeon). In fairness to my ENT colleagues, of whom I have many excellent ones, I find this not surprising. Any specialist physician is naturally inclined to do what they are trained to do. I suppose it’s also a version of the ancient saying I learned during my surgery rotations: “A chance to cut is a chance to cure.” So generally if your child’s physician refers you to an ENT specialist for recurrent acute ear infections, the recommendation will be for ear tubes. On the other hand, if the referral goes to a pediatric infectious disease specialist, the recommendation may well be for recurrent antibiotics as needed. So what’s the latest on which of these approaches is best? Before we get to that, I should provide some quick background on the cause of acute middle ear infections. If you want a deep dive into that question, you can find more information here.

Ear infections are extremely common in children, particularly toddlers. Estimates are that a quarter of children will have at least one by their first birthday and half will by the age of three. The cause is pretty well known. You can think of an ear infection as a complication of a viral cold, and toddlers get a lot of colds. Inflammation in the back of the nasopharynx blocks drainage from the Eustachian tube that connects the middle ear to the back of the nose. Bacteria normally living in the nose take advantage of this disruption to crawl into the middle ear and multiply, leading to infection. Toddlers are more susceptible because in them this tube is short and straight; as children age it lengthens and develops a kink, making it more inaccessible to bacterial invasion. This process is illustrated in the image below.

Antibiotics are used to kill the bacteria, which generally, but not always, works. But recurrences are common, often leading to multiple rounds of antibiotic treatment. The idea of tympanostomy tubes is to put a plastic ventilation device across the eardrum so that the middle ear has another way to get ventilated if the Eustachian tube gets blocked. After a year or two the tubes usually fall out, but by then the child is often at lower risk owing to age. There are pros and cons to both approaches: antibiotics are cheaper, but recurrent bouts of otitis can add up, and frequent courses of antibiotics carry problems; ear tubes are more expensive up front and they carry the risk of any surgical procedure. So which way is best? We have some useful new information to help parents choose.

The group at the University of Pittsburgh have been doing research on otitis media for a long time — Dr. Jack Paradise has been leading this effort for decades. That group recently published a randomized study in the prestigious New England Journal of Medicine: “Tympanostomy tubes or medical management for recurrent acute otitis media.” Although the study was randomized, meaning assignment of the children to the antibiotic group or the ear tube group was random, of course it couldn’t be blinded, since it’s obvious which group the child is in. Still, it is an excellently designed study. The article is accompanied by a useful editorial on what it all means. If you don’t read the article, I at least recommend the short editorial, even though the editorialist’s final conclusion reads a bit mealy-mouthed to me. So what did they find? The answer is both satisfying and not satisfying, depending upon your perspective, I suppose.

Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management.

To me, that’s kind of an odd way to put it, although I suppose the question they were getting at is if ear tubes are better, which their study shows they aren’t; the two approaches gave equivalent outcomes. Although the two approaches gave the same benefits, there are some differences between them in risks, and that’s where parental choice plays an important role. Recurrent courses of antibiotics carry with them risks of developing allergic reactions to them. There is also the issue of the relatively unclear risks of causing derangements in the normal bacteria living in our gut, since oral antibiotics indiscriminately slaughter masses of “friendly” bacteria. Certainly diarrhea is a common side effect. We are also always concerned about how excessive antibiotic use can lead to development of resistant strains of bacteria. On the other hand, any surgical procedure, even a relatively minor one like ear tubes, carries a slight anesthetic risk. I have also seen complications of ear tubes, such as persistent holes in the eardrum that won’t heal. Tubes can also fall out too soon and need replacement, meaning another surgical procedure.

An important point to understand is that this study is about recurrent bouts of ACUTE ear infections, not CHRONIC, persistent ear problems. Using ear tubes in chronic ear problems is an entirely different issue. If you’re interested in that debate, or if your child has that problem, you can read more about it here. But with recurrent acute ear infections, the editorialist correctly points out:

Thus, management decisions can be made jointly with a high degree of parental satisfaction.