Prenatal screens: Beware misleading results

Posted July 18, 2016 by Dr. Roy
Categories: Medical problems, Pediatric Insider information

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The Pediatric Insider

© 2016 Roy Benaroch, MD

A few years ago, I met a lovely couple at a prenatal visit. Although we usually do these visits in groups, this time we had arranged to get together privately, alone, when the office was closed, when there wouldn’t be other families and children around. I wanted to meet the family, but I didn’t want to be cruel. This wasn’t a typical visit, and I didn’t think they were going to be comfortable sitting in a room full of pregnant women, or a room with children running around. This couple expected their baby to die.

Prenatal screening, the parents told me, had shown that their baby had Trisomy 13. This is a genetic condition involving an extra copy of one chromosome. Most babies who have this do not survive long enough to leave the hospital; the few that do are severely ill, and have multiple health complications. The family had been offered an abortion, but had decided to proceed with the pregnancy. They were well-educated, and certainly realistic – though they had hope, they knew that there was very little chance that their baby would do well. Still, that was the chance they wanted to take. They had heard that I had some experience taking care of children with this condition, and wanted me on board if by some miracle their baby was able to survive, even briefly.

A few months later, Sally was born. And she was normal. She didn’t have Trisomy 13, or really anything else wrong with her, and she was able to leave the hospital in a few days. She’s about 18 months old now, and she’s a great little kid, with red hair, a picky appetite, and a little bit of a temper. Imagine what the parents went through, expecting her to die; and imagine how many parents, told of the grim news, would have elected to abort what would have been a healthy baby.

So what happened? Was the test just wrong? No – the test was done correctly, and the result of the test was, technically, correct. But it was misunderstood, by both the doctors and the parents.

The fundamental misunderstanding was that screening tests are not diagnostic tests. This comes up again and again in medicine, and every week I have to explain to parents why their screening tests for allergies do not necessarily mean that their child is allergic, or that the vision screening test doesn’t mean their child needs glasses. An abnormal mammogram does not mean a woman has breast cancer, and an abnormal prostate antigen blood test doesn’t mean that grandpa has prostate cancer. These are only screening tests, meant to estimate risk—they do not, ever, diagnose disease.

Let me go back to the test done on mom during her pregnancy. It’s called a “cell free DNA” (cfDNA) test, done on blood drawn from mom. During pregnancy, a few cells from the placenta burst, releasing their DNA into mom’s circulation. It’s a tiny amount of DNA, and it’s quickly broken down and cleared, but with some very clever genetic tools that miniscule fraction of fetal DNA can be isolated in mom’s blood, and measured. And it’s that DNA that’s tested to provide the results of the test. The cfDNA can detect conditions where the as-yet-unborn baby has an incorrect number of chromosomes, including Down Syndrome (that’s an extra chromosome 21), Trisomy 13 (an extra 13), other trisomies, or conditions involving the sex chromosomes. These conditions have tremendous implications for a baby’s health, so advance screening is desirable. cfDNA screening can be done easily and painlessly, on a small sample of mom’s blood, with no risk to the baby. Pretty slick.

But that’s the key word, screening. Though it’s testing genetic material from the baby, cfDNA is still a screening test. To really understand why, we’re going to have to do some math (feel free to skip this and the next paragraph if you want to just take my word for it.) The accuracy of a test is expressed by two terms: sensitivity (the number of positive tests divided by the number of people who truly have disease), and the specificity (the proportion of negative tests among a group of people without disease). The sensitivity and specificity of cfDNA testing is excellent – over 99%, which is the “accuracy” figure often quoted in marketing literature about these tests.

But in real life, what we really want to know isn’t the specificity or sensitivity of a screening test. What we need to know is its positive predictive value – that is, in a woman with a positive cfDNA test, what is the chance that her baby will truly have one of these health conditions? To figure that out, you need to apply Bayes Theorem, which requires not only the figures for the accuracy of the test, but the “pre-test probability”. In a screening population with an overall low risk of disease, even a very accurate test is going to have plenty of false positives. If you don’t believe me, follow that link and do some math examples.

Bottom line: for cfDNA testing in a 38 year old woman, the positive predictive value of a “high risk” screen for Trisomy 13 is 37%. (The pre-test probability depends on mom’s age – older moms have an increased risk of babies with chromosomal disorders. You can calculate both the positive and negative predictive values for cfDNA based on the age of mom here.) In other words, even with an abnormal cfDNA screen, the chance of this mom having a baby with Trisomy 13 was 37% — with a 63% chance of the baby being fine.

What should have happened after the abnormal screening test is what should always happen after an abnormal screening test – or, better yet, before the test is even done. Patients need to understand that a positive screen means the condition is “at risk.” Better yet, if there’s solid data, the actual risk percentage should be shared (37%, in this case.) Then the family could decide what to do next. After an abnormal cfDNA test, what should usually be recommended is a diagnostic test, to get a genuine sample of fetal DNA (typically though amniocentesis or chorionic villus sampling.) These diagnostic tests are very, very accurate – and in Sally’s case, if these were done, they would have shown that she did not have Trisomy 13.

But the amnio wasn’t done, in part because the doctors told mom, incorrectly, that the cfDNA was like an amnio, and that the result was conclusive. The doctors fully expected this baby to have Trisomy 13 and even made plans to not do a c-section if the baby ended up in distress. After all, she was going to die, anyway.

The results of screening tests should never be described as “positive” or “negative.” The best way to express the result is “high risk” or “low risk”. The language, here, is really important – and using the right language helps both doctors and patients understand what test results mean. One of the reasons I’m skeptical of patient-ordered tests is that patients may not understand what the results mean (though, admittedly, in this case her doctors didn’t seem to understand the results, either.)

Prenatal screening is a good idea, and cfDNA testing is a good tool. If you’re having these kinds of tests done, make sure you understand what the results mean, and make sure that you have a confirmatory, diagnostic test before you make any decisions that can’t be changed later.

Sally’s story is completely true (other than her name). Thanks to her parents for giving me permission to share it. 

 

Watson crick franklin

 

Should children hear voices in their heads?

Posted July 11, 2016 by Dr. Roy
Categories: Behavior

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The Pediatric Insider

© 2016 Roy Benaroch, MD

Missy wrote in: “My daughter casually mentioned last night that there is a person who is mean. I asked her more about it this morning and she says this person in her head tells her to say bad things. She says it sometimes scares her. She is 5 1/2 and is very imaginative. Mental illness does run in both sides of the family. How serious should we take this? What can we do? My daughter is funny, brilliant, and the sweetest child I have ever known. What can we do to help her?”

“Hearing voices” is common in children. A study of 3780 grade-school children in The Netherlands in 2009 found that over the course of a year, 9% of children reported hearing voices in their heads. Most of them weren’t bothered by it, though about 15% of them reported that the voices were troubling or disruptive. In a later study, the same authors found that most of these children (75%) said that the voices stopped within 5 years. So these voices are not usually a problem, and typically go away on their own.

Still, since Missy’s daughter is bothered by the voices, and they’re telling her to say “bad things,” I think a little more exploring is a good idea. I’d encourage the family to use these voices as a starting point to talk about what’s troubling her daughter, and (more importantly) what she can do about it. After all, for everyone, there’s always something that’s a problem. The goal isn’t to eliminate your child’s concerns or worries, but rather to teach them how to deal with them.

I’d start by telling the child that a lot of kids hear these things, or that Mommy used to hear them, too. (If that’s true – you might have to ask grandma.) How do the voices make you feel? Can the voices really make you do anything? What can you do if you don’t want to do the thing the voices say? Help your child understand that bad thoughts happen to everyone – but she doesn’t actually have to listen to them, and that she has the power to say to the voice, “No.” (Keep in mind that little kids are very concrete thinkers, and they are used to listening and obeying “rules”, and doing what they’re told. You may have to give her explicit permission, this time, to “disobey” the voice, and not feel badly about that.)

Ask her, “What is the voice telling you to do?” The answer might help both of you learn about what kinds of things are on your child’s mind. If the voice says “Push my little sister,” you could say, “I’ll bet sometimes you feel a little mad at your sister, and that’s OK. You can think those things, and that doesn’t make you bad.”

“Why” questions can sometimes be helpful, especially as kids grow a little older. “Why do you think a voice is telling you to steal candy?” Can open up a way to talk about the kinds of conflicting feelings that everyone has. On the one hand, you want the candy, because it tastes good; on the other hand, you know it’s not good for your teeth. These are tough dilemmas, for all of us, thinking things at the same time that contradict each other. Kids can start to understand how internal conflicts make all of us feel uncomfortable.

If the voices continue bothering a child, or seem to be contributing to behavior problems, the next step would be to get a referral to a mental health professional, typically a psychologist experienced with children. Ask your child’s doctor for references in your community.

While many children hear internal voices, it’s uncommon for teens and adults to continue to hear these (most of us perceive that our “internal monologue” is actually part of our own minds, and not projected from somewhere else.) As children mature into adults, continued thoughts “from outside”, especially if they’re “command thoughts” that tell you to do something, can be a sign of more-serious trouble. Other warning flags to look for include disturbances in mood or interactions with other people, hostility or paranoia, a lack of outward emotions, or unusual sleeping habits. While “hearing voices” isn’t especially worrisome in a child, seek additional help if this happens in teens or adults, especially when accompanied by other problems.

You're sort of confusing me, so, uh, begone... or, uh, y'know, however I get rid of you guys.

A stinky preschooler

Posted July 7, 2016 by Dr. Roy
Categories: Pediatric Insider information

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The Pediatric Insider

© 2016 Roy Benaroch, MD

Erika wrote in: “Is it normal for a 4 year old to have musty armpits? Only I can smell it because I jam my nose in her pits, but otherwise no odor emanates. But still, age 4?!?! Do I do nothing? I definitely don’t want to start deodorant or antiperspirants.”

After almost 20 years of seeing (and smelling) dozens of shirtless kids a day, I can promise you, yes, some of them do have their own odor. I suspect all of them, do, really – and in the mists of time, years ago, those odors were probably unique to each child and a way for moms to keep track of their little ones. These days, we expect cleanliness, anti-bacterial toothpastes, and children to smell vaguely of star anise, essential oils, and gluten-free pizza. But it wasn’t always that way.

If your kiddo is especially stinky (and it sounds like she isn’t – honestly, if you have to get your nose into her pits to find the odor, I think you need a new hobby) you can bathe her more, or insist she use a washcloth, or use a deodorant soap. It’s not really likely that an antiperspirant will help much at this age, because before puberty sweat is of the less-stinksome variety.

Speaking of puberty – I’ve been asked before of stinky young children, is this a sign of early puberty? Probably not, unless it’s accompanied by other things. Real puberty begins with breast development or increased testicle size (not, presumably, at the same time.)  There will also be a jump in height. Other things like pubic hair, body odor, and acne often begin around the same time, but actually aren’t caused by hormones from the gonads, and aren’t reliable signs of puberty. If you’ve got questions about your specific child regarding puberty, ask your doc, in person, during an exam. (Not over the phone. Honestly, I can’t tell without examining your child. And, please, don’t email photos. Someone could get arrested.)

Bottom line:  file this under “something else not to worry about,” and enjoy your little one, musty armpits and all.

Stinky Pete

Protect yourself from mosquitoes and Zika

Posted July 5, 2016 by Dr. Roy
Categories: Medical problems

Tags: , , ,

The Pediatric Insider

© 2016 Roy Benaroch, MD

I remember a trip to the Florida Everglades in about 1978. Surrounded by mosquitoes, alligators, and miles of swamp, our teachers told us that every creature was a vital part of the food chain, and essential to the ecosystem.

I hate those bloodsuckers. The mosquitoes, I mean. Not the teachers.

Mosquitoes are more than an itchy nuisance. Though uncommon, serious diseases such as West Nile Encephalitis and dengue fever can be spread by mosquito bites in the USA. Our newest worry, Zika virus, is especially dangerous to pregnant women and their unborn babies. Though it’s not yet been spread by mosquitoes in the continental USA, Zika will be here soon. Itchy mosquito bites can be scratched open by children, leading to scabbing, scarring, and the skin infection impetigo. Prevention is the best strategy.

Try to keep your local mosquito population under control by making it more difficult for the insects to breed. Empty any containers of standing water, including tires, empty flowerpots, or birdbaths. Avoid allowing gutters or drainage pipes to hold water. Mosquitoes are “home-bodies”—they don’t typically wander far from their place of birth. So reducing the mosquito population in your own yard can really help.

Biting mosquitoes are most active at dusk, so that’s the most important time to be vigilant with your prevention techniques. Light colored clothing is less attractive to mosquitoes. Though kids won’t want to wear long pants in the summer, keep in mind that skin covered with clothing is protected from biting insects like mosquitoes and ticks. A T-shirt is better than a tank top, and a tank top is better than no shirt at all!

Use a good mosquito repellent. The best-studied and most commonly available active ingredient is DEET. This chemical has been used for decades as an insect repellant and is very safe. Though rare allergies are always possible with any product applied to the skin, almost all children do fine with DEET. Use a concentration of about 10%, which provides effective protection for about two hours. It should be reapplied after swimming. Children who have used DEET (or any other insect repellant) should take a bath or shower at the end of the day.

Other agents that are effective insect repellants are picaridin, oil of lemon eucalyptus, and IR3535 (also known as ethyl butylactylaminopropionate. Tasty!) These are probably not more effective than DEET, but some families prefer them because of their more pleasant smell and feel. Other products, including a variety of botanical ingredients, work for only a very short duration, or not at all. The CDC has extensive info on these products here.

There are also yard sprayers or misters, devices that widely spray repellants or pesticides. I couldn’t find much in the way to independent assessments of these products, but there’s no reason to think they wouldn’t work. Still, I’m leery about the idea of spraying chemicals all over the place, when we know that DEET sprayed on your child is effective and safe for both kid and environment.

About “Organic” or “Natural” insecticides or repellants – those are just  marketing words. In the world of chemistry, the word “organic” means that the molecule contains carbon. Organic compounds are no more or less likely to be dangerous to people or the environment than non-organic compounds; likewise, “natural” in no way implies that something is safe or effective (or even “natural” in the sense that most people mean that term.) These words are tossed around as part of the typical salad of meaningless marketing-speak on labels. Ignore them.

There are also devices that act as traps, using chemicals or gas to attract the mosquitoes from your yard. Although I don’t have much independent confirmation that these work, they are probably environmentally friendly and safe.

Some children do seem more attractive to others to mosquitoes, and some children seem to have more exaggerated local reactions with big itchy warm welts. To minimize the reaction to a mosquito bites, follow these steps:

  1. Give an oral antihisamine like Benadryl, Zyrtec, or Claritin (do NOT use topical Benadryl. It doesn’t work, and can lead to sensitization and bigger reactions.)
  2. Apply a topical steroid, like OTC hydrocortisone 1%. Your doctor can prescribe a stronger steroid if necessary.
  3. Apply ice or a cool wet washcloth.
  4. Reapply insect repellent so he doesn’t get bitten again.
  5. Have a Popsicle
  6. Repeat all summer!

Updated and adapted from a post in 2013

There you will learn from Yoda

Goodbye, Flumist: Why science is important

Posted June 23, 2016 by Dr. Roy
Categories: In the news, Pediatric Insider information

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The Pediatric Insider

© 2016 Roy Benaroch, MD

Yesterday the CDC announced that its Advisory Committee on Immunization Practices (ACIP) voted to stop recommending the nasal spray flu vaccine, Flumist, for anyone. Bottom line: it doesn’t work. Though their recommendation against the use of Flumist still has to be approved by the CDC director to make it “official”, it’s pretty much a done deal. The AAP’s president has already endorsed the announcement, too.

Bye, Flumist. We’ll miss the ease of use and the not-scaring-children part, but the data’s clear. The mist doesn’t work. There was a sliver of good news, though—we have solid surveillance data from last year re-confirming that the traditional flu shot does work, with an estimated effectiveness of 63% last year. That’s not outstanding, but it’s pretty good. From a public health point of view preventing 63% of influenza cases can have a huge impact. Remember: every case prevented is one fewer person out there spreading influenza. Effective vaccinations not only help the person who got the vaccine, but the whole family and community.

Older data, at one point, had shown that Flumist was as effective (or even more effective) than the flu shot. For a few years, the mist was even considered the “preferred product” for children, because it seemed to work better.  Last year, Flumist lost its “preferred” status when data emerged showing that it wasn’t looking as good as the shot. Now, enough newer data has accumulated to show that at least against the strains that have been circulating recently, Flumist doesn’t work at all.

There’s going to be a scramble (again!) this year to ensure an adequate supply of injectable flu vaccine. I don’t know if MedImmune will suspend the Flumist program, or if they’ll still try to sell their product – but I am sure that there are a lot of docs out there scrambling this morning, trying to cancel Flumist pre-orders and increase our orders for alternatives. In the long run, that will be better for everyone. In the short run, it’s a problem. Families ought to plan to get their flu shots as early as possible this year, before they run out.

Science isn’t a set of answers, or a body of knowledge etched on a stone somewhere. It is a method of arriving at the truth, involving repeated observations and the continuous re-assessment of data. Estimates of vaccine effectiveness (and safety) are initially based on licensing studies, but they’re then adjusted by real-world data that continues to be collected, year after year. We should always make the best decision we can, based on the best data, even if that means we have to sometimes admit we’ve made a mistake, or that we have to change our minds. That’s not a weakness of science or medicine – that’s a strength. We can’t always promise to get it right, but we’ll keep studying and learning and trying to do it better.

Squirt!

Antibiotic overuse: Still a lot of room for improvement

Posted June 22, 2016 by Dr. Roy
Categories: Medical problems, Pediatric Insider information

Tags: ,

The Pediatric Insider

© 2016 Roy Benaroch, MD

We’ve heard it before: antibiotics just don’t work for viral infections. Docs know this, and I think most patients know this, but it’s an addiction we’ve had a hard time shaking.

Docs overprescribe because it’s fast, it’s easy, and it (might) increase patient satisfaction and return visits. That’s led to a cycle of reinforcing expectations from patients – who, after all, keep feeling better after the antibiotics. Of course they do. The minor viral infections that have been treated would have gotten better anyway. Still, it’s hard to shake that impression that it was the drug that made the illness go away. So next time, the patient expects and antibiotic, and doc is even quicker to prescribe it.

What’s the harm? Briefly: we’re encouraging the emergence of super-resistant super-bugs that, to put it bluntly, might just kill us all.

A study from 2015 illustrates some of the craziness and superstition that still guides a whole lot of antibiotic use:

The most-popular, most-prescribed antibiotic in the USA is “azithromycin”, known commonly as Zithromax. This top antibiotic is not recommended, first-line for ANY common infection—it’s not a good choice for ear infections, strep throat, or sinusitis. Not recommended for the top 3 reasons for antibiotic use, yet it’s still the top antibiotic*. Crazy.

Antibiotic prescribing varies tremendously by state. In Alaska, 348 scripts per 1000 patients per year; in Kentucky, it’s about four times that. Do they get four times as many bacterial infections in Kentucky? I don’t think so. Antibiotics, overall, are much more commonly prescribed in the southern states.

Another factor: counties with the most doctors – or the highest “per capita” number of people licensed to prescribe meds – have the highest rate of prescriptions. More docs doesn’t mean more preventive care, more access to good medical information, or better health. It does mean more prescriptions for antibiotics. (Why? I’d guess because it makes a practice more competitive and increases repeat business to write a lot of scripts.)

Current data shows that about 58% of antibiotic prescriptions handed out to human patients are for viral respiratory infections, including common colds or “upper respiratory infections”, viral sore throats, or ordinary “bronchitis”. None of these benefit from antibiotics in any way. Perhaps now’s a good time to revive the “Just say no” campaign.

There is some good news. There’s been about a 25% drop in antibiotic use since the 1990s, and I’m hearing from more and more patients who say right up front “we don’t want an antibiotic if we don’t need it.” That’s a very powerful message, and it’s something you ought to think about saying to your own doctor. You might think we’d only prescribe antibiotics if we genuinely thought they’d help… but the question is, who are they really helping? Probably not you.

*If you’re curious – why is Zithromax so popular, even though it doesn’t work well for any common infection? I think it’s because it can be prescribed with a very quick wave of the hand as a “Z Pak take as directed”. It’s so quick to write! So easy! Other meds need milligrams and instructions and things like “once a day” – who’s got time for that?! It also has a cool name. ZITH. Ro. Max! You may think I’m joking, but I’m not.

Medicine

Medicine

Lessons from my father

Posted June 19, 2016 by Dr. Roy
Categories: Pediatric Insider information

The Pediatric Insider

© 2016 Roy Benaroch, MD

Treat your teachers, bosses, and parents with humility and respect.

Treat employees and coworkers with humility and respect.

Heck, just be humble and respectful. You never know who you’re dealing with.

Put disappointments behind you, and look for the next opportunity.

Always ask for a better deal. It never hurts to ask. And don’t forget, treat the salesman with humility and respect.

Let other people talk. You’ll learn more from listening.

Let others underestimate you.

Work hard, and don’t complain.

Pay attention, and carefully collect the facts. But in the end, you’re going to have to take action. I think this was actually a lesson from Wild Wild West, which we used to watch together. We also watched Gilligan’s Island and Hogan’s Heroes, but I don’t recall as many useful life lessons from those shows.

Keep women happy. If you think of something nice to do for your wife, do it.

When dancing, the goal of leading is to make the woman look good. This applies not just to women, and not just to dancing.

For Salomon Benaroch, 1928-2008. I miss you, Dad. 


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