Archive for the ‘Medical problems’ category

The murky connection between maternal antidepressants and autism

December 15, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

A new study of almost 150,000 Canadian children is sure to further worry parents. Does taking antidepressants during pregnancy really increase the risk of your baby developing autism by 87%? As usual, the details matter. And the truth is never quite as clear-cut as the press release.

First: what we already know. Autism is a complex disorder of social behaviors and language. It’s unlikely that we’ll ever know “The Cause” of autism, because (like cancer and obesity and many other things) there’s probably not just One Cause. Certainly, genetics plays a huge role—siblings and other relatives of people with autism are at an increased risk for autism spectrum disorders. And we know that many prenatal factors (like premature delivery or maternal health problems) increase the risk, too. Some children with autism have a known genetic variant or marker, and the proportion of those kids seems to rise every year as our testing gets better. Still, there’s a whole lot we don’t know about other influences on how the brain develops, and on what other factors might contribute.

Previous studies on antidepressants taken during pregnancy have had mixed results—some gave shown an increased risk of autism, and others have not. One of the difficulties in doing such a study is that we know maternal depression, itself, is a risk factor for autism. So is it the antidepressant medicines that cause the risk, or the depression itself, or some other factor? For instance, depressed moms may get less sleep, or are perhaps more likely to drink alcohol, or may just feel more stressed—any of these, or any combination of these, could be what really confers the risk to the unborn baby.

In the current study, the authors tried to control for these effects by looking at multiple covariates. There’s some heavy-duty math behind these statistical techniques, but the idea is to isolate one independent variable (taking antidepressants) from every other variable, so you only “see” the effect of what you’re looking for. Of course, you have to know all of those other variables beforehand, and how to measure them, and how they might contribute to your end-point—and that’s why it’s tricky, and that’s why it’s easier to write about a press release than it is to read an actual study and muck your way through the details. In this study, the authors “controlled” for maternal health and mental health issues (though not specifically for maternal autism), substance abuse, income, education level, whether the family received welfare, and many other variables.

The authors used registries of births along with child and maternal health records from Quebec, looking at all babies born in 1998-2009. They excluded premature babies and twins (because these are already known predictors of autism), along with babies with other health problems. Then they looked at the child and maternal health records. To see if mom took antidepressants during pregnancy, pharmacy records were reviewed for filled prescriptions.

The numbers, themselves, are interesting. Of 145,456 live-born babies eligible, 1054 (.7%) were diagnosed with autism during the study period (typically within the first 6 years of life). Of those 145,456 babies, 2532 had moms who took antidepressants during the 2nd or 3rd trimester, including 31 who developed autism. When all of the math was done and covariates accounted for, the proportion of autism worked out to be 87% higher among the moms who took antidepressants after the 1st trimester (there was no increased risk during the 1st trimester, only during the 2nd and 3rd, or the last 6 months of pregnancy.)

That 87% increased risk—that pops, and that’s what you’ll see in the headline. But there are some other things to notice about the study that are more subtle, but just as important. Of the babies whose moms took antidepressants, 1.2% developed autism—and 98.8% did not. The relative increase in risk looks high, but the absolute, actual risk is still quite low. And the whole conclusion of the study rests on those 31 of the 150,000 babies who developed autism after exposure to antidepressants. That’s not a very big number.

I also wonder about controlling for known maternal risks. Perhaps more-severe depression itself confers a higher risk of autism than mild depression—and if more severely depressed moms were more likely than mildly depressed moms to take medication, that would explain the different observed rates. And maternal autism, itself—a friend of mine pointed out that the authors didn’t control for that, and didn’t even try to measure it. But if a higher proportion of moms with autism were depressed (which, logically, makes sense), that would also explain this association, without implicating the antidepressant medication itself.

What should parents do about this? Maternal depression can be debilitating, and needs to be treated—but perhaps non-medical therapy should be the best, first option, especially in the last 2/3rds of pregnancy. But if medication is needed to help mom, I think it’s still a reasonable option, given the small risks that could be implied by this study. It’s also clear from this study that antidepressants in the beginning of pregnancy, through the first trimester, are not associated with increased risks. Women on antidepressants probably don’t need to stop taking them while trying to become pregnant, or early on in the pregnancy.

If your child was exposed to these kinds of medications prior to birth, it would also be sensible to keep tabs on Junior’s development, and refer early on if there’s a concern of autism. Early therapy can be very effective.

People want a clear answer –“This” causes autism. It’s not that simple. This study supports the idea that early influences during pregnancy (such as maternal depression, or maternal medications) can be at least one risk factor. But there’s a whole lot more to learn.

 

Note: after I wrote this, someone sent me this link to NPR’s review of the same study – they did a good job, and provided links to previous research. They also made the point that the lead author of this study has worked with plaintiff’s attorneys who are suing antidepressant manufacturers. Should that color how we look at results like these? You decide.

 

Leo Kanner

Healthy teeth are happy teeth

December 14, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

Kaitlyn wrote in:

 

I know you’re not a dentist, but I have a few questions about fluoride and teeth. My daughter is five months and it seems to suddenly be a big source of concern. I’ve been told that you should start brushing your baby’s teeth as soon as they come in, but the advice on what type of toothpaste to use is conflicting. Some dentists say to use fluoride from the very beginning, while others recommend fluoride-free toothpaste until a child can spit it out properly, around age two. I’ve also seen people say that it’s not necessary to use anything besides water to brush a baby’s teeth until they’re one. Which method is really best, or is there not a very big difference when they’re so young? Also, I’ve recently heard that breastfed babies should be taking fluoride supplements starting at six months. Is that really needed, and if so does it still apply to breastfed babies with access to fluoridated water? I get that six month olds typically drink very little water, but I have been told you can give some with solid foods or between feedings at that age and I think I’d start to worry about her getting too much fluoride.

 

Many good questions! Let’s start with the fluoride. The old advice was that it was best to avoid fluoride toothpaste until age two. The concern had been that babies can’t spit well (ironically, they seem to spit up just fine when they want to), and that early fluoride could lead to fluorosis, or a staining of teeth. That worry is way overblown. The vast majority of children who’ve been exposed to excessive fluoride have minimal cosmetic changes that are only noticeable by a dental professional. Mild fluorosis actually strengthens teeth. An appropriate amount of fluoride toothpaste, when used very young, will lead to fewer cavities and better dental health.

What’s the “appropriate amount”? American Dental Association recommends a tiny dab, the size of a grain of rice. Even for older kids and adults, we’re only supposed to use a pea-sized amount. Those toothpaste commercials with the huge, ribbon-like blob? Those are meant to sell toothpaste, not give instructions on how to use the stuff.

About fluoride supplements for babies: they’re rarely needed for families consuming ordinary municipal tap water. Though six month olds don’t drink a lot of water, they should sip some with their meals, and many of their foods are made with water, too. If you’re drinking well water or live in an area without water fluoridation, ask your dentist or pediatrician more more-specific advice about your situation.

Speaking of water—one of the best ways to help keep your child’s teeth healthy is to encourage a “water habit” early on. People should drink water with meals (not juice, not soda). Set a good example, and don’t even offer juice to your child until… well, never. Juice is pretty much fruit with all of the good taken out. It’s just sugar water, really, and sugar water is not good for teeth or anything else.

When you start brushing baby teeth, remember the whole point of it is to develop a healthy lifetime habit. You have to keep it fun, even if that means you’re not doing a perfect job brush every single tooth. Use that tiny smidge of toothpaste, and make a game of it, and maybe even let your child take turns on your teeth. Don’t turn it into a struggle—if toothbrushing is unpleasant, it’s unlikely your child will ever get good at it.

As my dad used to say, “Take care of your choppers, and your choppers will take care of you!”

Choppers

“How high was the fever?” isn’t a very useful question

December 3, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

A September, 2015 study published in the Pediatric Infectious Disease Journal looked at whether fever itself – the height of a fever – is a good predictor of whether a child is likely to have a serious illness. And, once again, a common fever myth is shattered.

Researchers reviewed data from visits from children, aged 0-5 years, who presented to a pediatric hospital for fever in 2004-2006. (Yes, that was an oddly long time ago. I guess they write slowly in Australia. But in terms of the science, there haven’t been any big changes in vaccines or childhood illness since then, so I think the results are still valid.) Of the almost 16,000 fever episodes reviewed, about 1,000 children had what the authors considered a “serious infection”. That includes bacteremia (bacteria in the blood) in 64 children, pneumonia in 533, and urinary tract infection in 543. In total, only about 7% of the children had a potentially serious bacterial infection that needed to be treated. That percentage should be no surprise—we know that in the modern world, among vaccinated and healthy children, the vast majority of fevers are caused by viral infections that will get better on their own.

The authors then looked at whether the height of the children’s fever correlated well with whether or not they ended up having a serious diagnosis. They examined both the measured highest fever in the emergency department, and the parents’ self-reported “highest fever” in the last 24 hours, prior to their visit. Whichever way it was recorded, the height of the fever itself did a very poor job at discriminating between children who had and did not have a serious infection.

The statistics are complicated, and involve receiver operating curves that you may not be  familiar with—but, in the author’s words, “Measured temperature at presentation to hospital is not an accurate marker of serious bacterial infection in febrile children.”

Relying on the height of a fever resulted in both false positive and negative results. For instance, evaluating only those with a temperature of 100.4 or higher would still miss 1 in three serious infections. You can’t rely on high fevers as a positive predictor, either—only 1 in 6 children with a temperature of 104 actually had a serious infection.

The authors found that a few other observations could be at least somewhat predictive. Younger babies, overall, were a little more likely to have serious infections; and children who had had fevers for more than 4 days were also somewhat more likely to be diagnosed with something more serious (though I imagine those children also had more tests done, like chest x-rays. Perhaps they just found more illness when they looked for more illness.) But even when adding in considerations of age and length of illness, the height of the fever remained a poor predictor of the seriousness of the illness.

 

So what’s a parent to do?

First: prevent serious illness by making sure your children are up to date on their vaccines. We can prevent most causes of meningitis, pneumonia, blood poisoning, and other serious bacterial and viral infections with vaccines. Prevention is always better than having to evaluate and treat children in an emergency department or office visit.

Then: offer comfort care to children with fever. Extra fluids are a good idea, and if fever is causing a child to be uncomfortable, treat it. If Junior perks up and acts well after fever-reducing medication, and isn’t especially at-risk for serious infection**, treat fevers at home for a few days. If the child is getting worse, acting persistently sick, or isn’t getting better, go see your doctor. Remember: the number itself is less important than how your child feels and acts.

** This advice does not include any child less than 2-3 months old, or with an immune deficiency, or who isn’t up to date on vaccines for any reason. These kids are at much higher risk of serious or deadly infections, and shouldn’t rely on advice from the internet. Call your doctor for specific fever instructions.

 

More about fever:

What is a fever?

Why do kids get fevers?

Dispelling fever phobia

The fever action plan

 

fever rita moreno

Drug safety tip: Do not point nose spray upside down

November 12, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

 

Here’s a safety tip that makes sense—and it took a very simple study to show it. Nose sprays that are meant to be squirted with the bottle facing upwards shouldn’t be turned around to squirt medicine downwards.

Researchers from UCLA just published an eye-opening report on dosing of nasal spray medications. They studied oxymetazoline, a common OTC nasal decongestant spray marketed as “Afrin.” We know that 1-2 mL of this product (swallowed or sprayed into the nose) can lead to an overdose, including symptoms of slowed heart rate and breathing. We don’t worry about that, much, because the squirt bottle it’s packed in only delivers about 0.03 mL per squirt – you’d have to do over thirty squirts to reach a toxic dose. But that’s only if you use the squirt bottle correctly.

The investigators, instead, bought three different brands of oxymetazoline, and squirted it downwards, at a 45 degree angle, simulating what parents might do if they were squirting this into the nose of a child who is laying down. The volume delivered this way was between 0.6 and 0.9 mL for a single squirt—meaning, if both nostrils were hosed this way, you would almost certainly reach a potentially toxic dose.

With the help of my assistant, Blue Toad (who, ironically, doesn’t even have a nose), we’ve taken some helpful photos to demonstrate. Here, Blue Toad is getting a safe dose, using the bottle pointed upwards as designed:

Squirting up -- safe!

Squirting up — safe!

But here, Blue Toad is lying down, and the bottle is pointed down into his nose. Bad news for Blue Toad!

Squirting down? Bad idea!

Squirting down? Bad idea!

All medicines should be used carefully, following the directions—and the directions for this nose spray clearly say to hold the bottle upright. Still, I could imagine some parents trying to use this while their kids were lying down. Better to play it safe: make them sit up, and squirt up.

Homeopathy as good as antibiotics? No.

November 9, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

An August, 2015 study in Multidisciplinary Respiratory Medicine is being touted as evidence that homeopathy is as affective as antibiotics for respiratory infections in children. It doesn’t show that at all—in fact, it doesn’t show anything, except that crappy studies in crappy journals can nonetheless be used to manipulate opinion. Beware.

First, the study itself. Researchers in Italy looked at about 90 children with ordinary colds. All of them were given a homeopathic product that the authors claimed had already been shown to be effective for cough (that’s not actually true, but let’s let it slide for now.) All of the children did improve, as expected—colds go away, as we all know.

The “study” part was randomizing the children into two groups. One half of the study subjects only got the homeopathic product, the other half got both the homeopathic syrup PLUS amoxicillin-clavulanate, an antibiotic. You Insiders are already thinking—what, wait, what? You know that antibiotics have no role at all in the treatment of the common cold. Colds are caused by viruses, and antibiotics won’t make any difference. In fact, they’re very likely to cause harm, causing allergic reactions and gut problems and maybe triggering c diff colitis. It was entirely unethical for them to even give these antibiotics to the children, with not even an inkling of a reason to think they were a valid medical therapy. But they did it anyway.

The results are exactly what you’d expect. Both groups of children (the ones on homeopathy, and the ones on homeopathy plus antibiotics) did the same—their symptoms all improved over the weeks of the study. No surprise at all.

But the authors claimed “Our data confirm that the homeopathic treatment in question has potential benefits for cough in children…” The study didn’t show that all. They didn’t even look for that kind of effect—if they wanted to, they could have, by randomizing one group to receive homeopathy, and the other group to not receive homeopathy. But that kind of study wouldn’t show what they wanted it to show, so they didn’t do it.

You’re wondering, maybe, why did Multidisciplinary Respiratory Medicine even print this unethical, worthless study? The answer is here:

How much does it cost to publish?

 

Multidisciplinary Respiratory Medicine is what’s called a “predatory journal”, which charges high fees — $1,940 — to publish articles. These types of journals exist only to make money—there is minimal or no editorial oversight, and the whole point is to publish whatever someone will pay them to publish. The authors get their publication, and journalists and the public are fooled into thinking real science has occurred.

Another highlight – I’m not an investigative journalist, but looking at the full text of the article, I see under footnotes “The authors declare they have no competing interests.” Yet under acknowledgements, it also says “We thank Boiron SA, Messimy, France for a non-binding financial contribution.” Boiron is a huge producer and marketer of homeopathic products. And: when I Googled the lead author’s name + the word “Boiron,” I found this page, which features a video of him on Boiron’s site. No competing interests?

So, an unethical study comparing the wrong things claiming to show something it didn’t, published in a pay-to-play journal, paid for by a homeopathy company, written by a guy who is featured on said homeopathy company’s website. You still shouldn’t use antibiotics to treat a cold. And this study, like so many other homeopathy studies, shows only that homeopathy is a scam.

Phenylephrine: A placebo you don’t need

November 2, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

Doctors, myself included, are dismissive of placebos. “That doesn’t work,” we say, referring to countless therapies that have no benefit over fake therapies (placebos), including pediatric chiropractic, homeopathy, and acupuncture.

We need to be honest. We have our placebos, too—pushed by modern pharmaceutical companies and genuine medical doctors. Maybe we ought to spend more time cleaning up what we do rather than pointing fingers at them.

Case in point: phenylephrine, marketed as a nasal decongestant. To understand how phenylephrine (PE) became so popular, we’ll have to go backwards a bit, to 1994, when the FDA published a list of nasal decongestant products that it considered safe and effective. Anything on “the list” could be sold without further FDA review. Included on that list were two oral decongestants: phenylephrine and pseudoephedrine (commonly known by the brand name Sudafed), which was far more popular.

In the 2000’s, to combat the epidemic of methamphetamine abuse, Congress attached an amendment to the Patriot Act (yes, that Patriot Act), restricting the sale of pseudoephedrine-containing medications. You could still buy them, but in limited quantities, and you had to present your ID to the pharmacist so your purchases could be recorded and tracked. All pseudoephedrine-containing products were pulled from the shelves. And, predictably, sales suffered. People didn’t want the bother of confronting a pharmacist to buy Sudafed, and pharmacists frankly had better things to do with their time than check ID for $6 purchases.

The marketers, predictably, won: a whole slew of new products, containing PE instead of pseudoephedrine, hit the market, prominently displayed on store shelves. Names like “Sudafed PE” minimized the change in the active ingredients, relying on well-known brand names to sell the product. Within a few years, PE-containing products far outsold the hidden pseudoephedine products. And everyone was happy.

Well, almost everyone. If you had a stuffy nose, you were most certainly not happy. Because oral phenylephrine never actually worked. A 2007 review showed that the PE was no better than placebo, and the FDA considered removing it from the allowed-drugs monograph—but they were swayed by a different published analysis showing a small but positive effect of PE on one measure of nasal congestion. That study has been criticized on many grounds, including that it cherry-picked positive studies and ignored evidence that weighed against PE. Still, the FDA allowed PE to continue to be sold and advertised as effective—though they did request a solid, placebo-controlled study to settle the issue.

Now, finally, in 2015, a placebo-controlled study of PE has finally been published. It’s fairly large, using 539 adults, and it looked at multiple doses sizes of PE compared to placebo top treat seasonal allergic rhinitis. The results are unequivocal: PE, at every dose, works no better than placebo—meaning it doesn’t work at all. About 18% of study participants developed side effects, mostly headache (none were serious.)

I don’t know what the FDA is going to do with this information. They asked for it, and now they’ve got it. Perhaps they’ll pull PE from the shelves. Perhaps they’ll ask for more studies. Maybe they’ll say that the drug companies can no longer sell PE for allergies, but can continue to sell them for congestion caused by a common cold (there’s no evidence it works for that, either, but there are no big robust placebo controlled studies to cite.) For the time being, PE, the placebo, continues to be sold, and continues to be recommended by physicians. It’s hard to change habits.

If you’ve got a congested nose, there are some things that do work. Congestion can be relieved by saline washes or sprays or a steamy shower. If allergies are the culprit, a nasal steroid spray is very effective. Pseudoephedine (Sudafed) is still out there, though you have to ask for it. Topical nasal decongestant sprays (like Afrin) work, too, though should typically be used for only a few days.

Or, go with a placebo. If that’s your style, choose something safe, like a homeopathic product. It won’t relieve congestion any better than plain water, but at least it won’t hurt anything but your wallet. That’s more than I can say for phenylephrine and our other real-medicine-placebos.

Tea tree oil for lice (and many other things?)

October 19, 2015

The Pediatric Insider

© 2015 Roy Benaroch, MD

Alana wrote in:

My boy/girl twins will be 3 in December, and have just begun nursery school. It seems like reports of head lice are everywhere these days, and adding tea tree oil to shampoo (or using it as a spray on the hair) seems to be a popular recommendation for prevention. I thought that might be worth trying, thinking the worst thing that could happen is that it wouldn’t do anything and I’d be out a few bucks. But I did a little Googling, and it looks like there are some studies linking the use of tea tree oil to gynecomastia in boys.

Tea tree oil is one of those “natural” things that sounds like it has a use for everything, but I’m wondering if you know of any evidence that would suggest it should or shouldn’t be used? And if not, any other suggestions on lice prevention?

As Alana says, tea tree oil is indeed one of those things that seems to have use for almost everything—or at least that’s what you can find on Google. I quickly found sites suggesting it be used to freshening carpets, cleaning cuts and scrapes, treating fleas on your dog, making your breath fresh, taming asthma, and treating almost any skin condition from psoriasis to insect bites to body odor. And lice, too—preventing and treating lice both on you and your dog, apparently (yes, dogs can get lice, but not the same lice as humans. Lice are persnickety about whom they infest.)

Can one magic potion do all of that?

Tea tree oil is extracted from the leaves of the Melaleuca plant from Australia. It’s sometimes called a “tea tree”, but it’s a different plant from the one that drinking tea comes from. There’s also tea oil out there, which is meant for seasoning and cooking—that’s different stuff, too. Tea tree oil has become especially popular as one of many so-called “essential oils” often sold via multilevel marketing schemes. That term itself, essential oil, seems to be rooted in the alchemy of the middle ages, though it’s been newly popularized as a catch all for oil-based essences of plant fragrances and other compounds.

The best reference I could find summarizing what’s known about tea tree oil comes from the US National Library of Medicine’s Medline Plus database.  Some studies have shown it’s possibly effective when used topically for athlete’s foot, toenail fungus, and acne. There’s insufficient evidence to make a reasonable judgement about its use in any other health conditions.

Ice ice babyFor lice specifically, I looked through the Medline database for all relevant studies. There are a few, but the results aren’t really impressive. A 2007 study looked at tea tree oil along with other botanical and synthetic substances to prevent lice—including DEET, a commonly used insect repellant. Though tea tree oil did repel lice, it was only to a small degree, and the authors concluded that none of the tested products were effective at preventing lice.

In 2011, a blinded and randomized trial took hair clippings with attached lice eggs, exposing them to different essential oils (tea tree, lavender, eucalyptus) versus a standard “suffocation” type of product. Rounding off, the suffocation chemical killed 70% of eggs, and tea tree oil 45% — not great, though better than nothing.

A more-promising study from 2012 combined tea tree oil with the chemical nerolidol, and found good effectiveness against both lice and their eggs, at least in a laboratory setting (tea tree oil alone wasn’t as effective, especially against unhatched eggs.)

Net: no chemical treatment, whether based on botanical essential oils or any other chemical, seems effective at preventing lice. There’s some promise that tea tree oil might be part of a treatment regimen, but at least so far synthetic “traditional” lice treatment strategies are far more effective.

Tea tree oil is generally safe when used topically, other than occasional local irritation or a local allergic reaction. There was a report that continuous, high-surface-area skin exposure could cause estrogen-like effects (specifically, gynecomastia, the growth of breast tissue in boys), though it’s unlikely that short-term, limited use of this product would cause the same effect. Tea tree oil is poisonous and should not be ingested or used near the mouth.

Alana asked about preventing lice. What can work is trying to discourage children from wrestling, playing close, or sharing hair accessories. If lice do appear, stay cool. Remember that even though they’re icky, human lice do not spread any disease and are not a sign that your children are unclean or uncared for. There are a number of OTC and prescription products that can effectively kill lice (be sure to follow the directions, and repeat the process as directed.) Intense efforts to rid your child’s bed or your entire house are not necessary—the only lice that spread from child to child are the ones on heads. Lice that fall off are dead or dying, and are not spreading to other people.

More lice news: a 2014 study found that at least some louse eggs hatch as late as 13 days after they’re laid—which means that repeating lice treatment in 7-10 days may be inadequate (that is, it may leave some viable eggs ready to hatch.) Since most lice treatments don’t effectively kill the eggs, the timing of re-treatment needs to be both early enough so that newly hatched lice aren’t mature enough to lay new eggs, but late enough so that all eggs have hatched. If this 2014 report is correct, the best strategy may be to repeat the lice treatment twice—at 8 days and again at 15 days. It’s more complicated, but would effectively knock out all lice and eggs. Of course, no strategy will overcome the potential that your child will get lice back from another child at school—but, again, they’re still just lice, and we need to keep that in perspective. Itchy, yes. Icky, sure. But really, still, not something to get too worried about.

Related post: Don’t banish kids with lice