Sunscreen Safety and Oxybenzone

Is oxybenzone in sunscreen safe? From Squintmom/Beautiful EntropyI love getting questions about science-related issues from readers. I particularly love it when a question intersects with an issue I myself am curious about, as happened when a reader got in touch with me last week:

I need some advice about sunscreen. I just read some articles on CNN about new FDA guidelines and the Environmental Working Group’s 2012 sunscreen review. Of particular concern is oxybenzone. The FDA claims it’s safe and very effective at protecting against UVA and UVB rays. However, the EWG says that oxybenzone is carcinogenic. Hmm… use sunscreen to prevent skin cancer, but sunscreen causes… skin cancer? That seems like a big time conundrum to me. The other thing I wonder about is who is the EWG? All I really know is they came up with the “Dirty Dozen” foods you should always buy organic. So what’s the deal? Should I toss all of last year’s sunscreen with oxybenzone and buy new? Is the EWG generally a trustworthy, “non-woo” authority?

The oxybenzone molecule

Let’s start with my professional opinions of the Food and Drug Administration (FDA) and of the Environmental Working Group (EWG). The FDA is routinely accused by consumer groups and conspiracy theorists of being “in bed with Big Pharma,” engaging in cover-up operations, putting profit ahead of consumer health, and so forth. I really don’t agree with this take on the organization, as I discuss in this post. The FDA’s history in the US is one of a largely appropriate trajectory. They’re a behemoth organization, and as such, they move slowly. They’re slow to approve new drugs because they insist on rigorous testing; this is one of the things that pisses off consumers who want to see new drugs come to market quickly. They’re relatively quick to warn consumers if there’s evidence that a pharmaceutical or substance is harmful, though they’re not alarmist and rarely respond to the results of an isolated study. The FDA is, to put it simply, stuck performing an impossible balancing act: they’re under public pressure to approve substances quickly, while they’re simultaneously under public pressure to keep anything that could potentially be harmful off the market. These missions are mutually exclusive, and I have to say that for the most part, the FDA handles their task as elegantly as a behemoth government organization can do. Have they made mistakes? Absolutely. But what I appreciate about the FDA is that they correct over time, such that their trajectory is generally appropriate and stable.

The EWG, on the other hand, is far more alarmist than the FDA. They’re not a government organization, but are rather a research and lobbying group made up of citizens and scientists. A survey of toxicologists (unaffiliated with the organizations about which they were questioned) revealed that most felt the EWG overstates risks associated with products. Specifically, toxicologists gave the EWG an accuracy score of 4.2 (1 = significantly understates risks, 3 = accurately states risks, 5 = significantly overstates risks). By comparison, the FDA got a 3 from the toxicologists, indicating that they felt the organization was accurate in assessing and reporting risks. For those who are curious, the U.S. Centers for Disease Control and Prevention (CDC) and the American Medical Association (AMA) also scored near 3, reflecting accurate portrayal of risks, while Greenpeace got a 4.5 — the highest score given — for significant overstating of risks. The Pharmaceutical Research and Manufacturers of America (PhRMA), on the other hand, scored a 2.3 for being the most significant understater of risks. Note that PhRMA is not a government organization, and is not tied to the FDA, the CDC, or other government health regulators.

As far as the EWG goes, I think they have their place. They report on research, but often issue warnings on the basis of single studies or studies with limited applicability. Case in point, they warn consumers against sunscreen containing retinyl palmitate (vitamin A) on the basis of a 2009 study that looked at mice rubbed with the chemical and exposed to light. The vitamin A mice developed more tumors, leading the EWG to report a link between retinyl palmitate in sunscreen and cancer. However, there are significant issues that limit the study’s applicability. Most notably, sunscreen only ever contains a small amount of retinyl palmitate. Dose is very important in toxicology; any substance — even water — is toxic in sufficient quantity. As such, a pure retinyl palmitate rub applied to mice doesn’t provide information about the toxicity of small amounts of the compound in sunscreen. In the end, groups like the EWG help to promote research on issues pertaining to toxicology and public safety, but speaking for myself, I look for corroborating research or concern from more moderate institutions before acting on an EWG warning. In response to the question from the start of this post, I think we can safely say that the EWG is “non-woo,” but they are a little jumpy.

On to sunscreen safety. First and foremost, there’s a major risk-to-benefit analysis that one must conduct when determining whether to use sunscreen and what type to use. This is because the sun emits ultraviolet radiation (UV) that damages cells, leading to development of wrinkles, aging of tissues, and skin cancer. Sunburns are an indication of particularly severe cellular damage — just one or two sunburns before the age of 18 significantly increases risk of skin cancer later in life — but even a so-called “healthy” tan is a sign that damage has occurred. Sunscreen is a part of protecting the skin from sun damage, but it’s not the entire equation. In fact, staying out of the sun during intense radiation hours (midday) and using physical protection such as clothing, sunglasses, and hats provides the best protection from harmful UV radiation. No sunscreen provides complete protection. To this end, one of the new FDA regulations regarding sunscreen labeling is that sunscreens will no longer be allowed to refer to themselves as “sunblock,” on the grounds that this inappropriately overstates protection. While there’s been some muttering by the EWG and other groups about whether sunscreen truly helps to prevent skin cancer, these concerns are largely based upon use of sunscreens that protect from only one type of UV radiation (broad-spectrum sunscreens are best, but not all sunscreens are broad-spectrum) and inappropriate use of or reliance on sunscreen. The general consensus among medical and government organizations, including the CDC and the AMA, is that sunscreen is an important component of safe-sun behavior.

The active ingredients of a barrier sunscreen.

There are two major classes of sunscreens: barrier sunscreens containing minerals (like zinc oxide and titanium dioxide) that reflect light, and chemical sunscreens that absorb the light and prevent it from penetrating cells. There is essentially no risk of absorbing the barrier compounds through the skin, leading even the EWG to note that these sunscreens are likely the safest and most effective. In times past, barrier sunscreens were unpopular because they had a greasy white appearance on the skin (remember Zinka from the 80s?). Newer technology allows for smaller particles (nanoparticles) of barrier compounds, which are less visible on the skin, though some formulations may still be greasy. There’s also some question as to whether these nanoparticle formulations appropriately protect from UVA, one of the types of UV (UVB is the other type). Unfortunately, while the sunlight reaching Earth is made up of mostly UVA, the SPF rating on sunscreen applies to UVB protection only. The new FDA regulations propose a set of standards for reporting UVA protection, as UVA exposure also leads to skin cancer. With regard to barrier sunscreens, then, the most effective UV protection comes from the old-school stuff: greasy, white, and slathered on thick. The next most effective UV protection comes from a nanoparticle formulation combined with a chemical sunscreen containing oxybenzone or similar for enhanced UVA protection. Of course, protection from UV is only part of the equation when it comes to assessing sunscreen safety; the other part is the safety of the sunscreen ingredients themselves.

The active ingredients of a chemical sunscreen.

Oxybenzone is currently raising hackles at the EWG, and is one of the reasons that their Sunscreens 2012 report contains so few “approved” choices. The compound occurs in nature — it’s in flower pigments — and is incredibly common in personal care products. It’s not only a sunscreen, it’s also a fragrance enhancer, preservative, flavor enhancer, and so on. The CDC reports that a recent random sample of Americans revealed oxybenzone in 97% of urine samples (Calafat et al). However, the significance of this information has not yet been determined. The EWG calls oxybenzone a “potential hormone disruptor,” citing the European Commission on Endocrine Disruption (pdf) (ECED), which basically means that the EWG is saying they don’t like oxybenzone on the grounds that the ECED doesn’t like oxybenzone. As to why the ECED takes issue with it, they (like the EWG) are exceedingly cautious. The EWG cites two studies (Ma et al,* Ziolkowska et al) that show the potential for weak endocrine disruption. {Note that the Ma et al reference is incomplete on the EWG website, and I was able to find no evidence of it in the scientific literature}. The extent to which the results of these studies, conducted on cells with pure oxybenzone compound, are relevant to use of the compound in sunscreen are unknown. As the American Cancer Society points out:

Virtually all substances known to cause cancer in humans also cause cancer in lab animals. But the reverse is not always true – not every substance that causes cancer in lab animals causes cancer in people. There are different reasons for this.

First, most lab studies of potential carcinogens (cancer-causing substances) expose animals to doses that are much higher than common human exposures. This is so that cancer risk can be detected in relatively small groups of animals. But doses are very important when talking about toxicity. For example, taking a couple of aspirin may help with your headache, but taking a whole bottle could put you in serious trouble. It’s not always clear that the effects seen with very high doses of a substance would also be seen with much lower doses.

Second, there may be other differences between the way substances are tested in the lab and the way they would be used, such as the route of exposure. For example, applying a substance to the skin is likely to result in much less absorption of the substance into the body than would be seen if the same substance is swallowed, inhaled, or injected into the blood. The duration and dose of the exposure also help determine the degree of risk.

While the above refers to cancer risk, the same is true of other toxic effects of compounds that are revealed through laboratory and animal studies. With specific regard to cancer and oxybenzone, even the cautious EWG notes that there’s no evidence that oxybenzone is carcinogenic — or, more accurately, THERE IS evidence that oxybenzone IS NOT carcinogenic (non-mutagenic in 4 of 4 studies: CTFA, 1980; DHEW, 1978; Hill Top Research Labs, 1979; Litton Bioneics, 1979).

Taking all the information together and conducting a risk-to-benefit analysis, I think it’s fair to say that because of the limited data available and the availability of alternatives to oxybenzone, it may be worth avoiding it in sunscreen, but there’s no reason to get particularly excited about previous use or occasional future use. Given that it’s present in almost all chemical (non-barrier) sunscreens, this essentially leaves the barrier sunscreens containing zinc oxide and titanium dioxide. If one chooses to use the nanoparticle formulations with somewhat reduced UVA protection, one must then decide whether to use a chemical sunscreen for additional protection — but this once again leads to oxybenzone exposure.

One last thing: with regard to old sunscreen, if in doubt, throw it out. The CDC recommends that sunscreen be no more than three years old if there’s no expiration date on the bottle. If the bottle has an expiration date, abide by it. The protective chemicals in sunscreen break down over time, meaning that protection wanes.

Science Bottom Line:* Given that there is no sunscreen that provides complete protection, the evidence suggests that the safest choice (particularly for children) is the use of zinc oxide or titanium dioxide sunscreen (I prefer nanoparticle formulations for convenience and aesthetics), without a chemical sunscreen backup. This should be augmented through the judicious use of shade, clothing, sunglasses, and hats, particularly during the most intense periods of sunlight.

 

How do you protect your family’s skin outdoors?

 

References:

Calafat et al. Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National Health and Nutrition Examination Survey 2003–2004. Environ Health Perspect. 2008 Jul;116(7):893-7.

Ziolkowska et al. Endocrine disruptors and rat adrenocortical function: studies on freshly dispersed and cultured cells. Int J Mol Med. 2006 Dec;18(6):1165-8.

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Organic Versus Conventional Milk: Health Issues And Environmental Perspectives (Guest Post at Science of Mom)

I’m guest-posting today! Alice at Science of Mom has recently featured two articles about conventional versus organic milk; the first claimed that milk from rBST-treated cows was the same as (or even preferable to) milk from non-rBST-treated cows, while the second claimed that conventional milk was just as good as organic. As a chemist with a special interest in environmental and social issues, I have a different take. Here are the major points/conclusions:

  • Small, idyllic-sounding conventional family dairy farms (like the one described in in this recent guest post on Science of Mom) sound lovely. If everyone raised dairy cattle like she does, there’d be little reason to consider organic milk. However, farms like this one are the exception in the U.S. dairy industry, and are rare exceptions at that.  The vast majority of U.S. dairy cows are housed in animal feeding operations (AFOs), and specifically in concentrated animal feeding operations (CAFOs). By EPA definition, then, both AFOs and CAFOs are crowded, and CAFOs are major sources of environmental pollution.
  • Milk from dairy cows, regardless of how they’re raised, is free from antibiotics. However, antibiotic overuse — meaning use of antibiotics in a prophylactic sense and as necessary for treatment of diseases spread through unnecessary husbandry practices — is promoting the development of antibiotic-resistant bacteria. Because conventional operations including CAFOs promote the development of antibiotic-resistant bacteria (thorough antibiotic overuse) that then proliferate in the environment, it’s not necessary to have contact with or consume a conventionally-raised animal or product to be negatively impacted by these practices.
  • CAFOs produce tremendous amounts of concentrated environmental waste. There’s far too much of it for the land to absorb, so it runs off into the surface water (lakes and rivers) and leeches into the groundwater (aquifers that feed municipal supplies and wells). Excess nitrogen in the water is associated with acid rain, fish-kills, blue-baby syndrome (methemoglobinemia), and global warming.
  • Conventional farming practices result in dairy cattle consuming large amounts of chicken feces and chicken feed, which contains cattle meat. This cannibalization of cattle by cattle increases risk of spreading BSE (mad cow disease) in the U.S.
  • Conventional farms that use rBST increase the likelihood that their cows will suffer mastitis (an animal welfare issue.
  • Conventional dairy cattle have less access to pasture, which results in a different (and less healthy) fatty acid profile in the milk. Organic milk is higher in heart-healthy omega-3 fatty acids, while conventional milk is higher in pro-inflammatory omega-6 fatty acid.
  • In the end, organic milk is healthier for everyone: your family, the cows producing the milk, humanity as a whole, and the planet.

Read the full article at Science of Mom.

 

Should A Toddler Wear A Helmet On A Tricycle?

A sweet trike and helmet for a sweet girl!

My husband and I are both avid cyclists, recreationally and for commuting purposes. We both owe our lives, several times over, to helmets. Some of our crashes have been due to, shall we say, “operator error,” while others have been the result of collisions with vehicles. Aside from those crashes that were severe enough to have been potentially life-threatening, we’ve also both been in a number of crashes that would have likely caused traumatic brain injury (commonly called concussion) had we not been wearing helmets. It’s easy to dismiss the importance of wearing a helmet on a bicycle, scooter, or similar non-motorized vehicle, particularly if one doesn’t believe the risk of death is significant in the event of a crash (e.g., I’m just riding a cruiser down the sidewalk; I won’t die if I crash). Nevertheless, any time a person is thrown or falls from a moving bike or similar, there’s the significant risk of head injury. Further, there’s a growing body of research that links even mild traumatic brain injury to depression, cognitive impairment, and early-onset dementia (see, for instance, Guskiewicz et al [2005 and 2007], Kiraly et al). Even people who don’t ride a non-motorized vehicle in a way that makes death a significant risk in the event of a crash are at risk for traumatic brain injury, and its associated complications.

There’s some concern among physicians that the use of the term “concussion” confuses parents and downplays the seriousness of this injury (DeMatteo et al). It should be noted that a concussion is a traumatic brain injury, is associated with alterations in brain blood flow in children (Maugans et al), and can cause developmental delays and functional losses that persist months to years post-injury (Rivara et al). Traumatic brain injury is one of the leading causes of disability and death in children (Keenan et al.)

Last week, we decided W was old enough for her first tricycle. I found a really cool company called Wishbone that makes a 3-in-1; it converts from a low-rider trike for the toddler set to a low-rider bike, and finally to a taller bike for older children. Best of all, it has no pedals; it’s a so-called “run bike,” which allows little ones to work on refining balance and steering before having to coordinate pedaling action. And I love the company’s ethics and commitment to sustainability. Anyway, with the bike on order, we went and bought W a helmet. For a toddler. Riding a trike. With no pedals. No joke. There were a few reasons for this. First, while it might seem suspect that a toddler could fall off a trike and do any significant damage, there are actually many reports of serious trike injuries (see, for instance, Powell et al [1997 and 2000], Sacks et al, Sosin et al). Toddlers and preschoolers who fall off tricycles sustain head, face, and mouth injuries with great frequency, and researchers strongly recommend helmets for this group. Secondly, among toddlers, it’s not just accidents while riding that account for tricycle injuries; these not-yet-stable walkers can fall and sustain a head injury while attempting to mount or dismount a tricycle. The final reason we bought W a helmet was simply to get her in the habit early on, which has been quite successful even over the course of just a few days; if she wants to ride her trike, she points to her helmet. I’m happy to be getting her into this habit early, because the kid will be wearing a helmet every time she gets on a trike, bike or similar, rides a skateboard, or skis. Every time. And her parents will too, both because it sets a good example, because we know from experience, and because, as an article published in the Journal of the American Medical Association (Sacks et al) put it:

From 1984 through 1988, bicycling accounted for 2985 head injury deaths (62% of all bicycling deaths) and 905,752 head injuries (32% of persons with bicycling injuries treated at an emergency department). Forty-one percent of head injury deaths and 76% of head injuries occurred among children less than 15 years of age. Universal use of helmets by all bicyclists could have prevented as many as 2500 deaths and 757,000 head injuries, ie, one death every day and one head injury every 4 minutes.

 

Science Bottom Line:* Use a brain bucket. Wear a skid lid. Invest in some skull insurance. Don’t crack your melon.

 

Do you wear a helmet when you ride a bike? Do you make your kids wear one?

 

References:

DeMatteo et al. “My child doesn’t have a brain injury, he only has a concussion”. Pediatrics. 2010 Feb;125(2):327-34. Epub 2010 Jan 18.

Guskiewicz et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005 Oct;57(4):719-26; discussion 719-26.

Guskiewicz et al. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 2007 Jun;39(6):903-9.

Keenan et al. Epidemiology and outcomes of pediatric traumatic brain injury. Dev Neurosci. 2006;28(4-5):256-63.

Kiraly et al. Traumatic brain injury and delayed sequelae: a review–traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. Scientific World Journal. 2007 Nov 12;7:1768-76.

Maugans et al. Pediatric sports-related concussion produces cerebral blood flow alterations. Pediatrics. 2012 Jan;129(1):28-37. Epub 2011 Nov 30.

Powell et al. Bicycle-related injuries among preschool children. Ann Emerg Med. 1997 Sep;30(3):260-5.

Powell et al. Cycling injuries treated in emergency departments: need for bicycle helmets among preschoolers. Arch Pediatr Adolesc Med. 2000 Nov;154(11):1096-100.

Rivara et al. Disability 3, 12, and 24 months after traumatic brain injury among children and adolescents. Pediatrics. 2011 Nov;128(5):e1129-38. Epub 2011 Oct 24.

Sacks et al. Bicycle-associated head injuries and deaths in the United States from 1984 through 1988. How many are preventable? JAMA. 1991 Dec 4;266(21):3016-8.

Sosin et al. Pediatric head injuries and deaths from bicycling in the United States. Pediatrics. 1996 Nov;98(5):868-70.

Are Vaccines Safe?

The World Health Organization (WHO) has declared the week of April 21, 2012 to be World Immunization Week. The purpose of the initiative is to spread information about the importance and safety of vaccines.

The question are vaccines safe and effective? weighs heavily on many parents. I’ll admit that even I, as staunch an advocate of vaccines as you’ll find anywhere, pondered that question on my way to the pediatrician with W. Not that I didn’t ultimately trust — no, KNOW — that they are both. Rather that the doctor was going to Stick A Big Needle! In My Baby! Regardless of where a mother or father stands on the vaccine issue, we’ve all had to answer this central question in our own minds.

Edward Jenner, By Vigneron Pierre Roch (1789-1872)

As this is World Immunization Week, I want to take some time to acknowledge and thank the father of modern vaccination, Edward Jenner. Dr. Jenner was an English country doc, born in the mid-18th century. During his time, smallpox was still very much epidemic, and was deadly in up to 60% of infected adults and 80% of infected children. Jenner was intrigued by the fact that milkmaids didn’t generally contract smallpox. They did, however, contract an illness called cowpox early in their milking careers. Cowpox wasn’t particularly serious. The milkmaids recovered and went on to live full cow-milking, smallpox-free lives. On the basis of these observations, Jenner inoculated (this word means to introduce an infective organism) several individuals with pus from an infected sore on the hand of a milkmaid with cowpox; this was the first modern vaccination. The vaccinated individuals felt a little sore and feverish, but did not contract full- blown cowpox. Those that Jenner vaccinated — including his own 18-month-old son — though certainly exposed in the course of everyday life, did not contract smallpox. They proved immune to the disease.

A child with smallpox, 1973. Photo from the CDC.

As parents, we might recoil in horror at the thought of a mad scientist father “experimenting” on his baby boy. Let me make it clear, though, that all this took place well before the development of germ theory (the notion that bacteria and viruses cause disease). Jenner and his contemporaries didn’t know WHY people got sick, they simply knew that people DID get sick (this actually adds to Jenner’s brilliance). As such, there would have been no possible mechanism for testing the vaccine in a laboratory, on animals, or anything of that nature. Jenner’s only options for testing his theory would have included stabbing a random passerby with cowpox pus and then exposing the unwilling victim to smallpox (not ok!), collecting many willing volunteers from the general public (not likely, since most people were afraid that if they were injected with cowpox pus, they’d grow cow limbs*), or using a combination of his own family and a very few willing volunteers. The natural question, of course, is did he vaccinate himself? The answer is no, but only because he was already immune to smallpox, having been inoculated as a boy through the hideously dangerous practice of purposeful exposure to the scabs and pus of smallpox patients.

*This seems ludicrous, I know. Then again, we’re 200 years after the fact now, and we can look back and laugh. Similarly, I’m sure the notion that vaccines are linked to autism will amuse future generations, who will think us peasants for having entertained that fear.

Some people shake their heads and say Jenner may have been a good doctor, but what a horrible parent, to expose his son to such risk. I would counter and say Jenner WAS a good doctor. Such a good doctor that he was DARN sure his theory would hold water. Such a good doctor that he wanted his theory tested so that, if accurate, it would literally save millions of lives. And I suspect he agonized about it. We don’t know; that part isn’t on record. But I suspect Jenner asked himself, in his own way and as we all do, will this be safe and effective? Then, too, there’s the fact that Jenner wasn’t exposing those he vaccinated — including his son — to a deadly disease. Rather, he was exposing them to cowpox. He suspected (and was correct) that they wouldn’t get a full-blown case of cowpox, but even had they done so, that wouldn’t have been a serious consequence. He didn’t vaccinate his son just to test a theory. He vaccinated his son because he believed in his theory, and wanted the boy protected from the disease. He engaged in some scientific critical thinking — a risk-to-benefit analysis — and decided that the risk of contracting cowpox was nothing compared to the benefit of immunity from smallpox.

Jenner has been strongly criticized in modern anti-vax circles for his “questionable experiments.” For instance, the website Vaccine Side Effects states:

Convinced of the virtue of vaccination Edward Jenner inoculated his 18-month-old son with swinepox, on November 1791 and again in April 1798 with cowpox, he died of tuberculosis at the age of 21 [sic]. James Phipps was declared immune to smallpox but he also died of tuberculosis at the age of 20.

That is to say, inoculating the children caused them to contract tuberculosis and die. This is out-and-out ludicrous. First of all, tuberculosis was rampant at that time, and was responsible for the death of about 25% of the population. Not 25% of the infected population, 25% of the ENTIRE population. Let’s put that another way; any one otherwise healthy person had a one-in-four chance of dying from tuberculosis. This makes it entirely unremarkable that both the boys referred to above died of the disease. Note that Jenner vaccinated many, many children, and the overall rate of death from tuberculosis among the vaccinated was no different than that in the general population. Oh and also? Tuberculosis is completely unrelated to pox, be it cow, small, or otherwise. The quote above is tantamount to saying The flu shot causes death! Every single person who gets the flu shot dies! Some of them die of heart attacks! Some die of strokes! Some die by overdosing on meth! The flu shot causes heart attacks, strokes, and meth use!!!

Those among us who are uncomfortable with Jenner’s experiments can rest assured that things are different now. Armed with germ theory and mechanisms for testing medical hypotheses in the lab long before they’re ever tested on people, no one needs to expose their toddler son to a microorganism in order to advance the science of medicine, or to a vaccine that hasn’t been tested in hundreds of different ways for safety and efficacy.

These days, smallpox exists only in biological laboratories. Photo from the CDC.

In any case, modern vaccines (named for the cows that carried the cowpox Jenner used to inoculate those early patients — vacca is Latin for cow) have indeed saved millions of lives. The CDC has a page that’s well worth a read on what would happen if we stopped vaccinating today. So Edward Jenner, during this World Immunization Week 2012, let me just say thank you. Thank you for being an excellent scientist, a true naturalist, an observer of the world and generator of ideas. Thank you for following through in testing your hypotheses, despite public fear and negativity. Thank you for being willing to put your own family on the line to save so many lives. Thank you for advancing the field of immunology. Thank you for the modern vaccine. Thank you.

On May 8, 1980, the World Health Organization officially endorsed a resolution declaring the global eradication of smallpox. Modern vaccinations are based upon the theories developed by Edward Jenner during his work with cowpox and smallpox.

 

What do you think about Jenner and his work?

 

 

2011 U.S. Measles Rates Highest In 15 Years

I’m willing to bet he would have been happier with the shot.

Misconceptions and fear have been fueling the anti-vaccination movement in recent years, particularly with regard to the measles, mumps, and rubella (MMR) vaccine. This is in part because a study published in The Lancet that linked the MMR vaccine to autism (Wakefield et al). In addition to rampant misinformation spread via the Internet, the Wakefield study continues to fuel public concern, despite thorough and unanimous scientific debunking by more than 20 studies (Poland), retraction by all but one of the authors – Wakefield himself — and retraction by The Lancet.

Unfortunately, despite overwhelming scientific evidence that the risks associated with the MMR vaccine are small and uncommon, particularly relative to the serious and more common risks associated with contracting the measles, some parents continue to refuse to immunize their children.

A report by the U.S. Centers for Disease Control and Prevention (CDC) not only underscores the significant risks associated with being unvaccinated for the measles, it also helps demonstrate the fallacious nature of many of the arguments against vaccination and highlights the importance of vaccination in protecting the community.

According to the CDC report, there were more measles cases reported in the U.S. in 2011 than in any of the prior 15 years. A total of 222 cases were reported, the majority of them in people less than 20 years of age. 65% of cases were in unvaccinated individuals, and another 21% of cases were in individuals whose vaccination status was unknown or not on record. Of those who were unvaccinated, a fraction (27 total cases) were under 12 months of age, and were therefore too young for the vaccine.

In light of this disturbing report, some common myths about measles…and the facts:

Myth: Measles is exceedingly rare in the U.S., as vaccination rates are generally high. Unless my children will be traveling to Europe or other parts of the world with higher measles rates, they don’t require measles protection.

Fact: While measles isn’t as common in the U.S. as it is elsewhere in the world (there were no U.S. cases in 2000, for instance), it’s imported from other countries (either by foreign travelers or by U.S. travelers returning from a measles-prone area) and can spread in the U.S., mainly due to unvaccinated individuals. Measles is contagious for about four days before any rash appears, meaning that travelers from foreign countries can bring the disease to the U.S. without being aware that they are doing so. The CDC notes that most cases of measles in the U.S. were brought in from Europe. Further, measles is so contagious that casual exposure to an infected individual (even one who doesn’t yet show signs of the disease) is very nearly 100% effective in transmitting the infection. Measles is spread through the air, meaning that it’s possible to get the disease without any physical contact with an infected individual.

Myth: Measles is a common, routine childhood illness, and there’s no reason to vaccinate for it.

Fact: Measles was common in the U.S. before the introduction of the vaccine in 1963. The disease is so contagious that essentially 100% of the population contracted it prior to the development of the vaccine. Simply because a disease was once common, however, does not mean it is “routine” or harmless. Measles complications are relatively common, and include severe dehydration and pneumonia. 32% of individuals who contracted measles in the U.S. in 2011 had to be hospitalized for complications. Thankfully, there were no deaths among these individuals. However, swelling of the brain and death are possible complications of the disease, occurring in about 3/1000 cases. Even among the individuals who do not require hospitalization, measles is a truly miserable experience. It comes with a high fever, which is accompanied by muscle aches, headache, and sensitivity to light. Unlike chicken pox, to which measles is sometimes erroneously compared because they both cause skin rashes, measles is respiratory and causes a dry cough and extremely sore throat, which contributes to dehydration. The rash can be very extensive (in many cases, it enters the mouth), and itches.

Myth: The MMR vaccine is more dangerous than the measles.

Fact: The MMR vaccine is associated with some mild side effects, including an innocuous and temporary rash in about 5% of vaccinated individuals. Moderate side effects, such as seizure, are very rare, occurring in about 1/3000 doses. Note that the moderate side effects (which are not life-threatening) are three times rarer than the risk of death from the measles. Serious side effects of the MMR vaccine, including death, are so rare that they can’t be statistically quantified. In other words, people die so rarely after getting an MMR that no one can be sure the death was due to the shot.

Myth: Since almost everyone in the U.S. is vaccinated against measles, my child will be protected.

Fact: The vast majority of U.S. citizens are vaccinated against measles. This means that measles won’t be able to take hold and spread across the country in the form of an epidemic, as it could have done before 1963. However, the disease can still spread from one individual to the next, particularly in areas of lower MMR compliance. The 222 cases of measles in the U.S. were primarily due to small outbreaks (there were 17 such outbreaks), where the average outbreak size was 6 individuals. Put another way, for every one case of measles brought into the country by a foreign traveler or returning U.S. citizen, five people who had never left the country got sick.

Myth: If I choose not to vaccinate my children, I’m not hurting anyone but my own family.

Fact: This is not so. To protect a group of people from a disease as effectively as possible, it’s important to keep the vaccination rate as high as possible. The fewer unvaccinated individuals in a population, the less likely that someone with measles will come into contact with an unvaccinated individual, which reduces the likelihood of an outbreak. Vaccines are highly effective — vastly more so than most other medical treatments — but they’re not 100%. This is especially true in children who have had only one of their MMR shots (the CDC recommends a booster at age 4-6). Maximizing the number of immunized individuals helps to protect those for whom vaccination may not be effective. There are also those, including babies under one year of age, who are not eligible for vaccination. Maximizing the vaccination rate among the eligible minimizes the risk to vulnerable members of the population.

 

If you vaccinate, do you worry about those who don’t? If you don’t vaccinate, what about it makes you uncomfortable?

 

References:

Poland. MMR Vaccine and Autism: Vaccine Nihilism and Postmodern Science. Mayo Clin Proc. 2011 Sep;86(9):869-71.

Wakefield et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children [retracted in: Lancet. 2010;375(9713):445]. Lancet. 1998;351(1903):637-641.

Should I Vaccinate My Child for Chickenpox?

With W’s first birthday behind us, we’ve got 12-month shots in our immediate future. In addition to the panoply of vaccinations she’s been getting at her shot visits for the last year, she’s up for MMR and varicella (chickenpox) this time around. The MMR shot is one I am fervently in favor of, despite the fact that it’s one of the vaccinations most targeted by anti-vaxers. There’s a bit of discussion of the MMR vaccine in this SquintMom post, and there’s quite a bit more information here.

Photo by Jonnymccullagh, from Wikimedia Commons

While my feelings about MMR are unequivocal, I spent the weekend doing some research into the varicella vaccine, as I knew less about it. The anti-vax rhetoric I’ve heard suggests that the varicella vaccine is a bad idea because:

1)   it’s risky

2)   it could wear off in early adulthood

3)   chickenpox is a routine childhood illness

Normally, I don’t put too much stock in anti-vax rhetoric, but I had chickenpox myself (unlike measles), and it (obviously) didn’t kill me, so I’m more predisposed to sympathizing with the argument that chickenpox is a routine childhood illness than I am to agreeing with the same statement about measles. (Though it’s worth noting that since I had chickenpox when I was three, I don’t really remember it. In all likelihood, it was completely miserable, and if I could remember the experience, I’d probably be moved to vaccinate W purely out of sympathy. It’s very easy to sit in an armchair with chickenpox immunity and refer to it as a “routine childhood illness.”) The real sticking point for me — and the reason I did some extensive literature-searching on the topic — was that the vaccine is new (and it might wear off in early adulthood; we don’t know yet), and unlike many other illnesses, chickenpox is actually more serious in adults than in children. I looked into the varicella vaccine to convince myself that I wouldn’t be exposing W to increased risk of chickenpox later in life by vaccinating her now.

The varicella vaccine (sometimes given in combination with the MMR as the MMRV shot) is recommended by the CDC for all children ages 1-12, as well as for anyone over 13 who does not have evidence of chickenpox immunity. Anti-vax rhetoric suggesting that the vaccine is risky is erroneous. The vaccine is a live, attenuated (weakened) virus, and there is a very small chance of getting a mild rash upon vaccination. Serious side effects, including allergic reaction and seizures, are so rare that they can’t be definitively attributed to the vaccine (they’re so rare that they could be due to nothing more than chance). The most common side effect is soreness or redness, which is an indication that the immune system is working. This soreness is mild, and occurs in about 20% of people.

While the risk of a serious reaction to the varicella vaccine is too small to be accurately measured, the risk of death from chickenpox is much more significant. Of every 100,000 infants under 12 months infected with chickenpox, eight will die. Older children have a lower risk of death, but still die at the rate of two in 100,000 (Preblud et al). Far more common complications include bacterial infection of pox sores — which can lead to scarring — and febrile seizures. Chickenpox also typically results in a week or more of lost school time (plus a lot of misery) for children, as well as lost work time (plus sleeplessness and sympathetic misery) for the caregiver. Based upon an analysis of the relative risks, the chickenpox vaccine carries a lower risk of serious complication than acute effects of the chickenpox illness.

It’s also worth noting that anyone who develops chickenpox is susceptible to herpes zoster (shingles) later in life. The chickenpox virus is never fully eradicated from the body. Instead, those who get chickenpox eventually recover from their symptoms, but the virus remains dormant in the nerve cells. Later in life (typically in adults over 60, those under severe stress, and/or those with compromised immune systems), the virus can become active once again. The resulting rash is very painful, and can lead to scarring. It’s also often associated with symptoms of illness, including fever and joint pain. By preventing infection with chickenpox, a vaccinated child is spared the potential for developing shingles later in life.

There have been some popular media reports that the varicella vaccine is responsible for increased shingles incidence. This is true, but only in one sense. Several studies, including Hardy et al, show that as expected, those vaccinated for chickenpox are less likely to get shingles than those who develop the chickenpox infection. However, as more and more young people are vaccinated for chickenpox, the incidence of chickenpox infection falls in the population. Consequently, adults who had chickenpox as children don’t get a natural “immune boost” from being exposed to chickenpox on a regular basis. This makes shingles more likely in these adults (Edmunds et al). Eventually, as the number of vaccinated individuals overtakes the number of individuals who have had chickenpox, the shingles rate will decline. It is a factual misrepresentation to claim that the chickenpox vaccine increases the risk of shingles.

As to the longevity of the vaccine, any “new” vaccine (and it’s worth saying that a vaccine goes through years — even decades — of testing before it’s ever available to the public) is associated with some uncertainty about how long it will last. Some vaccines appear to confer lifetime immunity; adults don’t need MMR boosters, for instance. Other vaccines confer only a few years of immunity, including the Tdap (for tetanus, diptheria, and pertussis), which has to be given every 10 years. Anti-vax rhetoric suggests that since the chickenpox vaccine could wear off in early adulthood, vaccinated children would be at risk for chickenpox infection as adults. This is an erroneous claim, however; the CDC and health organizations worldwide are monitoring the longevity of varicella vaccine-conferred immunity. According to the World Health Organization, studies in Japan indicate that the vaccine is effective for at least 20 years (studies are ongoing), while ongoing studies in the U.S., which started later than the Japanese studies, indicate that the vaccine is still effective after 10 years. In the end, it doesn’t matter whether the vaccine’s effectiveness wears off after a number of years; booster vaccinations will be recommended if health organizations deem them necessary to maintain immunity. Note, too, that since the varicella vaccine has been recommended for all children in the U.S. since 1995, surveillance organizations have had 17 years to observe the first group of vaccinated individuals for waning immunity (and, of course, there’s been even more time to observe the test-case individuals for waning immunity). A child vaccinated for varicella today will know years, if not decades, in advance of the need for a booster shot.

After looking at the research, I’m impressed by the effectiveness of the varicella vaccine. A meta-analysis (study of many studies) by Seward et al revealed that a single dose of the varicella vaccine was 84.5% effective at preventing any chickenpox infection, and was 100% effective at preventing severe chickenpox. Since chickenpox infection is severe in 52% of cases in unvaccinated children (Vazquez et al), this is a significant reduction in risk. Current CDC recommendations are for two doses of vaccine, given at least three months apart, which increases the effectiveness of the vaccine to around 90% (AAP).

The other thing that occurs to me is that, given the tremendous prevalence of the varicella vaccine among US children, parents who don’t vaccinate their children put them at risk of NOT catching chickenpox. Yes, you read that right. Of course, they’re at risk of catching chickenpox, because they’re unvaccinated. But even worse would be to NOT catch chickenpox (as a child), and then catch it as an adult (because while chickenpox incidence is falling in the US, the disease has not been eradicated, and will not likely be eradicated any time soon). It’s essentially incumbent upon parents who don’t vaccinate their children to ensure that the child catches a sufficiently serious case of the chickenpox to help prevent susceptibility later in life. However, in ensuring that the child catches the chickenpox, the non-vaccinating parent also puts that child at risk for serious chickenpox-related complications and later shingles, meaning that the risks associated with not vaccinating are particularly complex in the case of varicella!

 

Science Bottom Line:* The varicella (chickenpox) vaccine is less risky than chickenpox infection, making it an essential childhood vaccination. Despite the relative newness of the vaccine, there’s evidence of at least 10 years of protection (studies ongoing). The CDC continues to monitor immunity of vaccinated individuals, and will recommend booster shots for vaccinated individuals if they are determined necessary.

 

Did you (or will you) vaccinate your child for chickenpox?

 

References:

American Academy of Physicians. American Academy of Pediatrics. Committee on Infectious Diseases. Varicella vaccine update. Pediatrics. 2000 Jan;105(1 Pt 1):136-41.

Edmunds et al. The Effect of Vaccination on the Epidemiology of Varicella Zoster Virus. J Infect. 2002 May;44(4):211-9.

Preblud et al. Deaths from varicella in infants. Pediatr Infect Dis. 1985 Sep-Oct;4(5):503-7.

Seward et al. Varicella Vaccine Effectiveness in the US Vaccination Program: A Review. J Infect Dis. 2008 Mar 1;197 Suppl 2:S82-9.

Vazquez et al. The Effectiveness of the Varicella Vaccine in Clinical Practice. N Engl J Med. 2001 Mar 29;344(13):955-60.

What The Science Says About Circumcision: Part 2 — The Risks

There are many different techniques and mechanisms by which circumcision occurs. Since the purpose of this series of posts on circumcision is to address routine infant circumcision in the hospital environment, I will not be addressing alternate circumcision practices, including non-hospital (religious ritual) circumcision.

Photo by Robert Valette, Creative Commons

Last week, I addressed the scientific evidence as it pertained to the benefits of circumcision. My conclusion was that there was no strong scientific evidence to support routine infant circumcision in the United States.

This week, I want to address the issue of harm; that is to say, is there evidence that routine infant circumcision carries significant, scientifically documented risks?

There are four common arguments given in opposition to routine infant circumcision. These are:

1)   It is painful, and therefore cruel and/or damaging to the infant;

2)   It results in diminished sexual function;

3)   It is associated with a high rate of complications;

4)   It results in long-term psychological trauma.

In this post, I will address the evidence for each of these in turn.

At one time, it was thought that neonates didn’t experience pain, didn’t distinguish it from non-painful stimulus, or couldn’t encode it. This was used as a justification for circumcision without analgesic. Later, it was thought that the injection of analgesic would be just as painful as circumcision without analgesia. Many studies have shown these notions to be false, including a study addressed in a previous post (see, for instance, AAP Statement, Fabrizi et al, Taddio et al). Pain-relieving options include a numbing topical cream and a dorsal nerve block (Brady-Fryer et al). However, neither of these completely eliminates pain during the procedure. Another nerve block, called a ring block, appears to be quite effective (Lander et al, Shockley et al). Further, in combination with other pain-relief methods, oral sucrose (sugar) also helps reduce discomfort (Razmus et al). The Lander study points out that not only does the ring block provide very effective analgesia during the circumcision procedure, the block injection itself is significantly less painful than non-anesthetized circumcision. Other analgesic options, including oral sucrose and topical numbing creams, can reduce the discomfort associated with the nerve block injection.

With regard to the notion that circumcision results in lasting damage due to the physical pain, there is some scientific evidence to support this in the case of circumcision with no analgesic. According to Taddio et al, infants circumcised with no analgesia had a greater pain response to subsequent noxious stimulus (vaccination) than infants circumcised with topical cream pain relief, who showed a greater response to the painful stimulus of vaccination than uncircumcised infants. The study did not examine the responses of infants circumcised with a ring block, however. Neither did the study note any effect persisting beyond the neonatal period. A review of the literature suggests that there is no scientific evidence to support the notion that circumcision (with or without analgesia) causes changes to pain response that persist beyond the neonatal period. Further, while some anti-circumcision advocates (sometimes called “intactivists”) suggest that circumcision causes brain damage and/or physical changes to the brain, there is no scientific evidence to support this notion. Studies that show a correlation between neonatal pain and changes in brain structure/function (such as Anand et al) are based upon repetitive exposure to pain, and can’t be generalized to one-time medical procedures.

Some argue that circumcision results in diminished sexual sensation and/or function. This is actually an untestable claim. It’s possible to compare the sexual function of men circumcised as infants with that of men not circumcised as infants, and it’s possible to compare the sexual experience of an uncircumcised adult male with his experience post-circumcision (in the case of a man circumcised as an adult), but it’s not possible to know what a man circumcised in infancy would have experienced had he never been circumcised. As such, none of the scientific evidence regarding sexual function and infant circumcision is particularly relevant or helpful, and can’t be used to support a strong argument either for or against the statement that circumcision affects sexual function.

One study of men circumcised as adults suggests that function may be affected, but finds that more men experience improved function than diminished function after circumcision (Fink et al). Of 123 men circumcised during adulthood, 38% reported harm in the form of perceived diminished function. 50%, however, reported improved function. Unfortunately, since 93% of the study participants underwent circumcision for medical reasons, the results of this study can’t be generalized to the population.

Unbiased studies have uncovered only anecdotal accounts (Moses et al) of sexual effects, which can’t be taken as scientific evidence (see this post for an explanation of why anecdotes aren’t scientific evidence). There are men who attribute their sexual dysfunction to infant circumcision, but there is no scientific evidence to support these claims. Some “intactivist” arguments suggest that female sexual partners of uncircumcised males derive greater sexual pleasure than do the partners of circumcised males. There are no scientific studies to support this. In fact, the few scientific studies that exist suggest the opposite. Ugandan women report greater sexual satisfaction from intercourse with circumcised men, despite the fact that circumcision is not routine practice in Uganda (Bailey et al). Surveys of college-aged American women show overwhelming preference (87%) for the appearance of a circumcised penis (Williamson et al).

There are a few survey studies of sexual function and attitudes about circumcision. One such survey (Hammond) showed strong evidence of sexual dysfunction and psychological trauma as the result of infant circumcision. However, it must be noted that the Hammond study did not sample the population randomly. Instead, study participants were asked to respond to a survey from the National Organization to Halt the Abuse and Routine Mutilation of Males (NOHARMM), an organization whose very name betrays its bias. As such, it’s not reasonable to generalize the findings of the Hammond study to the population at large, since the men most likely to participate in the voluntary survey would have been those who were dissatisfied with their circumcision. A much larger survey by Laumann et al found that of 1400 American men, those who were circumcised were actually less likely than uncircumcised men to report a sexual dysfunction. While the foreskin has sensory function (Taylor et al), there is no scientific evidence to suggest that the loss of these receptors affects sexual satisfaction or the intensity of the sexual experience for men. One study even goes so far as to suggest that while there isn’t currently evidence to support the notion that circumcision somewhat desensitizes men, even if such evidence existed, it wouldn’t necessarily be a bad thing, given that more men (and their partners) complain of premature ejaculation than complain of inability to achieve orgasm (Burger et al). While Burger doesn’t go so far as to suggest circumcision to prevent problems with premature ejaculation, these observations do put into perspective the “intactivist” argument that circumcised men don’t enjoy sex as much as they otherwise would; clearly, for the vast majority of men, enjoying sex isn’t a problem. The scientific evidence does not support the notion that male circumcision diminishes sexual performance in men, nor sexual satisfaction in men or women.

Regarding the notion that routine infant circumcision is associated with a high rate of complication, this does not stand up to scrutiny. The American Academy of Physicians (AAP) has reported a complication rate of 0.2-0.6%, though it’s difficult to accurately assess the rate of complication, since different surveys include different symptoms as complications of circumcision. As such, some studies suggest higher rates of complication, though they define “complication” very differently (including aftereffects that can’t necessarily be attributed to circumcision). On the flip side, Wiswell reports that approximately 10-15% of males who are not circumcised as infants have recurrent balanitis (swelling of the foreskin) or phimosis (foreskin that doesn’t retract), and require circumcision later in life. The adult procedure is a more significant surgery than the infant procedure, leading some practitioners to view circumcision as “preventative medicine.” Not all cases of balanitis or phimosis require surgical treatment, however, meaning that Wiswell’s numbers don’t translate directly into a percentage of uncircumcised men who will require adult circumcision. Based upon the numbers, there is not adequate evidence to suggest that routine infant circumcision is particularly risky.

Finally, with regard to the argument that infant circumcision results in psychological trauma, the support for such a notion is anecdotal and unprovable. “Intactivists” argue that many (some even go so far as to say most) circumcised men are traumatized by their circumcision, and that those who don’t acknowledge the trauma are in denial. This is a spurious claim; one could just as easily make the argument that children born by cesarean section are traumatized by not having experienced a vaginal birth, and that those individuals born by cesarean who don’t acknowledge their psychological pain are “in denial.” The denial argument is a powerful-appearing one for the “intactivists,” since by definition, any man who denies being in denial is categorized as…in denial. Still, we can make an attempt to sort through the science. A very large (5000 individuals) British study showed that circumcised men scored no differently than uncircumcised men on a variety of behavioral and psychological tests (Calnan et al), indicating that if the circumcised men were at all “traumatized,” it was undetectable to psychologists and didn’t affect their behavior. In a position paper, a psychiatrist and anti-circumcision activist compares circumcision to sexual abuse and an assault on the body (Goldman), but there’s no evidence to support the validity of the former, and the latter comes from the statements of young Turkish boys ritually circumcised without analgesic in a public ceremony, so it can hardly be generalized to anesthetized neonates in a hospital setting.

Goldman continues by suggesting that infant circumcision is associated with long-term psychological effects. As evidence for this, he cites the reports of men who contacted the Circumcision Resource Center (CRC). There are two problems with using this group, and their anecdotal reports of psychological harm, as evidence that circumcision has a psychological impact upon the general population. First, the men were “self-selected,” meaning they don’t represent a random selection of the population. To consider these individuals representative of the population is tantamount to making the claim that most Americans believe in extraterrestrials on the basis of those select individuals who contact SETI (Search for Extraterrestrial Intelligence) to report them. As with people who feel strongly enough that they’ve seen an alien to warrant a call to SETI, those who contact the CRC represent the small minority who feel particularly strongly about their circumcision. While it would be wrong to discount the intensity of their individual feelings, neither can one reasonably generalize those strong feelings to circumcised men as a whole. Furthermore, though SETI may claim (or even attempt) to be impartial and scientific in their search for evidence of extraterrestrial life, they are nevertheless predisposed to a particular outcome, and therefore their conclusions may reflect a bias. Similarly, the CRC is predisposed to find evidence that circumcision leads to harm. A second important point with regard to those men who contacted the CRC (and again, this is not meant to downplay their psychological pain) is that since no man has a conscious memory of INFANT circumcision (the brain doesn’t work that way), it’s pure conjecture on the part of a man to suggest that his psychic trauma is the result of his circumcision. He might feel regretful that he was circumcised, or he might wish he hadn’t been, but these feelings could as easily be the result of events he experienced post-circumcision (the emotions conjured by which he falsely attributes to the circumcision in a post hoc ergo proctor hoc fallacy). Even Goldman, who is clearly biased toward showing that circumcision causes harm, can only conclude that “the connection between present feelings and circumcision may not be clear.” In essence, that leaves the psychological trauma argument insufficiently supported from a scientific perspective. While some men may be traumatized by circumcision (though again, whether infant circumcision was the root cause of an individual’s feelings of psychological trauma is impossible to determine), there’s no scientific evidence to suggest that routine infant circumcision has lasting psychological effects.

 

Science Bottom Line:* There is no scientific evidence that strongly links routine infant circumcision with appropriate analgesia to physical or psychological harm.** Because there are many options available for managing pain during infant circumcision, however, there’s simply no justification for medical circumcision without analgesia.

 

**Obviously, this is not to say that no one is ever hurt by circumcision, or that there are not individuals who wish they hadn’t been circumcised. However, the SCIENTIFIC EVIDENCE does not provide support for the argument that routine infant circumcision is harmful. As such, the argument AGAINST circumcision in the U.S. can’t be made on the basis of scientific evidence, and must instead be made on the basis of values and beliefs.

 

What do you think about the risks of circumcision?

 

References:

AAP. Circumcision policy statement. American Academy of Pediatrics. Task Force on Circumcision. Pediatrics. 1999 Mar;103(3):686-93.

AAP. American Academy of Pediatrics: Report of the Task Force on Circumcision. Pediatrics 1989 Nov;84(5):761.

Anand et al. Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior? Biol Neonate. 2000 Feb;77(2):69-82.

Bailey et al. Acceptability of male circumcision as a strategy to reduce HIV infection in Uganda. AIDS Care. 2002 Feb;14(1):27-40.

Brady-Fryer et al. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004217.

Burger et al. Why circumcision? Pediatrics. 1974 Sep;54(3):362-4.

Calnan et al. Tonsillectomy and circumcision: comparison of two cohorts. Int J Epidemiol. 1978 Mar;7(1):79-85.

Fabrizi et al. Electrophysiological Measurements and Analysis of Nociception in Human Infants. J Vis Exp. 2011 Dec 20;(58). pii: 3118. doi: 10.3791/3118.

Fink et al. Adult circumcision outcomes study: effect on erectile function, penile sensitivity, sexual activity and satisfaction. J Urol. 2002 May;167(5):2113-6.

Goldman, R. The psychological impact of circumcision. BJU Int. 1999 Jan;83 Suppl 1:93-102.

Hammond et al. A preliminary poll of men circumcised in infancy or childhood. BJU Int. 1999 Jan;83 Suppl 1:85-92.

Lander et al. Comparison of Ring Block, Dorsal Penile Nerve Block, and Topical Anesthesia for Neonatal Circumcision. JAMA. 1997 Dec 24-31;278(24):2157-62.

Moses et al. Male circumcision: assessment of health benefits and risks. Sex Transm Infect. 1998 Oct;74(5):368-73.

Razmus et al. Pain management for newborn circumcision. Pediatr Nurs. 2004 Sep-Oct;30(5):414-7, 427.

Shockley et al. Clinical inquiries. What’s the best way to control circumcision pain in newborns? J Fam Pract. 2011 Apr;60(4):233a-b.

Taddio et al. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997 Mar 1;349(9052):599-603

Taylor et al. The prepuce: specialized mucosa of the penis and its loss to circumcision. Br J Urol. 1996 Feb;77(2):291-5.

Williamson et al. Women’s preferences for penile circumcision in sexual partners. J Sex Educ Ther. 1988; 14: 8.

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