Antibiotics and the Tooth Fairy

Let’s put it out there: this is a very high stress time. Most days, I feel like the only time I’m actually relaxed is the ten minutes after I finish running in the morning. The next week is not likely to bring very much relief. Regardless of what you are doing for the holiday you’re probably feeling anxious about it, or sad, or both.

But there is some good news to cling on to. One thing I will highlight: the vaccine news is great. A 95% effective vaccine is really more than we could have hoped for. This is a light at the end of a tunnel, even if not an immediate one.

Side note: someone asked me to explain what 95% effective means. Here we go, briefly. In these trials they take a big sample of people (30,000 to 40,000) and randomly assign them to get a vaccine or a placebo shot. They then observe their chance of being infected. The placebo arm of the trial — the non-vaccine group — gives you a sense of the number of expected infections without the vaccine. By looking at the difference between the number infected in the vaccine group and the number you’d expect in the placebo group, you figure out the efficacy.

For example: if you see 100 infections in the placebo group, and 5 in the vaccine group, that tells you that 95 of the infections that you would have expected based on the placebo group rate were blocked by the vaccine. So that’s a 95% effective vaccine.

It is true, I will note, that some people who are vaccinated did get the virus (although notable in the case of the second vaccine, the Moderna one, there were no serious cases in the vaccinated group, suggesting the vaccine did provide some protection even in people who got the virus). But this is always true, and 95% is a very high protection rate. Flu vaccines are rarely above 60%. Measles vaccines — a gold standard — are 93 to 97% effective.

Overall: really, really positive news. We just need to keep people safe until we can actually roll this out.

Today, I have a couple of quick fun things, and then I will address the many, many emails I got asking about the new study on antibiotics and kids.

Fun Stuff about Teeth

I have two fun things about teeth (okay, the first is more “fun” and the second is more “informative”)

First, someone asked me if I would post their survey on what you tell your kids about the tooth fairy. Here it is. Please take it! There is no deep research question here but I’m interested to see the results (which I will post!). I’m not going to bias you by telling you our own approach, but I promise I’ll tell all at some point…

Second, in response to my post on toothbrushing some actual pediatric dentists offered to write some responses to the questions I posed at the top of the post and to genearlly provide some reflections. I loved what they wrote, and you can read it here. Huge thank you to Dr. Sean McGivern, Dr. Stephanie Vargas and Dr. Donielle Williams for putting this together. It’s much more specific than I was able to be, and I suspect you will all find it helpful.

Antibiotics & Babies

Many, many of you wrote me panicked emails earlier this week about news coverage of a new study on antibiotics and infants. The study (link to PDF here) argues that exposure to antibiotics before the age of two was associated with a higher risk of many, many conditions in childhood. Specifically, the study found increase risks of asthma, hay fever, eczema, celiac disease, being overweight or obese and having ADHD. The rhetoric in the study and media coverage is somewhat alarmist. Many people wrote to me to say their Facebook groups are considering shunning antibiotics.

Before I air my list of grievances with the statistics here (it’s long! get ready!) let me say two general things. First: it is generally agreed that antibiotics can be over-used. When I was a kid every time you went to the doctor with a fever they’d just give you penicillin. We know now that was a mistake. Many childhood illness are viral and antibiotics will not work, and overuse contributes to resistance. Doctors are now taught not to prescribe antibiotics unless they know there is a bacterial infection.

HOWEVER, second: antibiotics are really, really valuable for treating bacterial infections. It is hard to understate the benefits the world has gotten from the invention of penicillin. If your child has a bacterial infection — ear infection, urinary tract infection, etc, etc — they should be treated with antibiotics. Living in the developed world, in this era of basically good health (minus COVID-19), it can be easy to forget that treatable bacterial infections kill a lot of people. It would be a shame for a study like this to push people away from antibiotics they need.

With that intro, let’s dive in.

The basic structure of this paper should be familiar to any of you who read this newsletter regularly. It’s an observational study of about 14,000 children. The authors have data on antibiotic exposures before the age of 2 and on health conditions among children as they age. The data is from official medical records, based on prescriptions and diagnoses, so is likely to be well measured. The papers compares their various outcomes — obesity, asthma, ADHD, etc — across children who took antibiotics during their first two years (70% of children) and those who did not. Broadly, their conclusion is that for most of these conditions there is a correlation between antibiotic exposure and worse later health.

In some of the media I read on this they were careful to refer to this link as an “association” and not “causal.” That’s good, because the attempts to address issues of selection in this paper are extremely limited, even relative to most papers in this space. Normally, we’d see authors in studies like this adjust for differences like maternal education, family income, other risk factors (prematurity, low birth weight, etc) in all of their analyses. The primary analyses in this paper do not adjust for anything. In some secondary figures and the Supplemental Appendix (always check it out!) they do show results with some adjustments, but since their measure of antibiotic exposure seems to change between the main results and these additional results it is difficult to see how much the controls matter.

This adjustments for confounding variables is made more complicated by the fact that key variables are missing for a large share of the sample (30% missing birth weight, more than 10% missing maternal education) and have to be imputed. I can’t tell quite how they impute them; they reference a general R package for doing this, but do not give specifics.

On top of this, it’s hard to make heads or tails of some of the patterns in the results which they emphasize. For example: developing atopic dermatitis (eczema) is associated with receiving 3 to 4 antibiotic prescriptions before the age of 2, but not with 5 or more. Exposure to cephalosporins (a particular type of antibiotic) is associated with the largest number of conditions, although penicillin prescriptions are responsible for the effect of celiac disease. Penicillin is also associated with a lower risk of autism, whereas cephalosporins are associated with a higher risk.

The authors also distinguish timing. The effects on ADHD appear for both sexes for prescriptions before 6 months, for neither for prescriptions between 6 and 12 months, and for only girls for prescriptions between 12 and 24 months. I have no idea why this would be. In general, the paper gives only a very limited sense of why we might see these relationships. They discuss the microbiome, which we think is important and is in principle affected by antibiotics, but our understanding of this mechanism is very poor. Certainly nothing we know would suggest these random patterns of links at different age groups.

What do I think is, in fact, driving the results in the paper if it is not causal relationships? One obvious possibility is basic differences across families — income, education, etc — which correlate with health and drive the results. A more precise mechanism is that illness is linked over time. For example: we know that kids who have bronchitis as a complication of viral infections early in life are more likely to show up with asthma later. This would appear here as a link between antibiotics (prescribed for the bronchitis) and asthma, but of course it wouldn’t be the fault of the antibiotics. A third possibility is that this is all capturing diagnosis. Some parents are more likely to seek health care, making their children both more likely to be prescribed antibiotics early in life and diagnosed with health conditions later. Some of these conditions (for example, hay fever or eczema) often go undiagnosed by a doctor because they are mild. This means that differences in diagnosis probability may play a role.

I do not know which of these are driving the results, perhaps it is all three, or yet some other thing. What I am confident about is that one should not take these results as causal. Is it possible that antibiotics affect the microbiome and have some small, longer-term impacts on children? Of course. Nothing in this paper rules that out. But nothing in the paper rules it in, either. I hope I do not have to say this but if your child is ill with a bacterial infection, please give them their antibiotic prescription. And if you have done this in the past, please do not now feel guilty about it.

Weigh in!

Keep the thoughts coming. I cannot write back to everyone but I do read all of your emails, I promise.

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