Can taking too many antibiotics be harmful to children?

Can taking too many antibiotics be harmful to children?

My kid has fever again. I am sure you are all familiar with that moment, as parents (or maybe as grandparents).
Whether you’re the type of parent that rushes to the doctor’s office for every little fever that spikes up and whether you are one of those who book a doctor’s appointment just to rule out an ear infection, a throat infection or a respiratory infection.
The moment when your child’s fever rises is when you ask yourselves whether this episode requires antibiotics. I mean, he’s been ill so many times this month, and this is probably the third round by now. And you’re just over it.

Sometimes, even if the pediatrician is convinced that your child has a viral infection and you know, very well, that antibiotics are not beneficial for a viral infection, the thought of maybe, just in case still runs through our mind. You think to yourself, that the worst-case scenario is that it will be useless, but at least it will give you the peace of mind that your child is covered. What’s the worst that can happen if I give my child just a little bit of antibiotics when he doesn’t really need them?

The medical literature has attempted to answer the latter question through an article that was published in the Journal of Infection (PMID 35021114) several months ago, a systematic review and analysis of all the data that has accumulated so far with regards to the long-term effects of antibiotics on children. But before we dive into this article and its results let’s just say that generally speaking, the widespread use of antibiotics has two major negative impacts – one at a community level (resistance of bacteria to antibiotics in a specific area/country), and the other at an individual level.

This article discusses the negative impacts at the individual level, similar to a previous article that I summarized here that discussed the effect of antibiotics on a child’s immunity.

Anything related to how antibiotics cause the emergence of resistant bacteria in the community-setting will not be discussed here.

Introduction – Statistics have shown that about two thirds of children are first exposed to antibiotics before the age of two and that more than half are exposed to antibiotics more than once a year.
Together with the antibiotics’ increasing efficacy and ability to reduce complications that may follow infectious illnesses, there has been a concurrent increase in the incidence of allergies, asthma, inflammatory bowel disease, rheumatological diseases, obesity, diabetes, autism, attention deficit and hyperreactivity disorder and more with the rising use of antibiotics.
Investigators then began asking themselves whether these two are associated and an important theory that one should be familiar with when it comes to this topic is ‘The Hygiene Theory.’
The hygiene theory claims that a decrease in exposure to different infectious pathogens has brought about an increase in the incidence of situations and illnesses that are mediated by the immune system. How are these two related?
By exposing our immune system to different pathogens, we are able to train and teach it when and what it should react to and by doing so, decrease the risk of disequilibrium in the system. Let’s just say that when we administer antibiotics to children, we decrease the prevalence of different infections but increase the risk of instability of the immune system, as well as the risk of development of immunity-mediated illnesses.
This theory is associated with the microbiome – a concept that is growing more popular and important in the medical world today. The microbiome refers to the community of bacteria that is naturally present in the different parts of our body (mostly in the intestines but also on the skin, mouth, ears and whatnot). The microbiome is an inseparable part of our general health and plays a role in many different processes in our body, including ones related to the immune system and our metabolism. Obviously, antibiotics selectively harm that same “friendly” community of bacteria and create a new equilibrium that may tip the scale over and bring about the development of illnesses. There are studies that have shown that even a single, brief exposure to antibiotics can be fatal to that same community of bacteria, and that if it happens to occur at a bad cosmic timing, it may bring about the potential for the development of illnesses, again.

Methods – So how can one put together such a systematic and comprehensive study? Or in medical words – a systematic-review and meta-analysis?
Medical databases were scanned according to different criteria and pre-set settings for all available literature covering the effect of antibiotics on children under the age of 18. Since a surplus of information exists, and not all the data out there is of high enough quality, the studies that were found were narrowed down to include quality papers that were suitable for analysis. In this paper the authors were able to attain 160 studies that overlooked 21 different effects in 22,103,129 children. Pretty impressive, right?

Results – The results that such studies reveal are always complicated because the data is inconsistent among the different manuscripts reviewed and the conclusions depend on how each effect is defined and calculated. For example, consider the basic definition of what exposure to antibiotics could mean. But let’s forget about definitions for a minute and try to be more practical and so we can understand the bottom line. The bottom line here is the relative increase in the risk of developing a certain illness after being exposed to antibiotics compared to the risk without exposure.
The results are as follows:
The risk of developing wheezing and asthma – almost double.
The risk of developing food allergies and atopic dermatitis – approximately 38% greater.
The risk of developing allergic rhinitis/allergic eye infections is 75% greater.
The risk of developing Juvenile Idiopathic Arthritis is 20% greater.
The risk of developing obesity is 20% greater.
There was no statistically significant association between exposure to antibiotics and the risk of developing inflammatory bowel disease, celiac, diabetes mellitus type I and psoriasis.
There is limited data with regards to the association of antibiotics and developmental delay or autism but three of the studies showed an association with development of attention deficit and hyperreactivity disorder and learning disorders.

Here’s an anecdote – there is a research that studied the association between colic in infants and exposure to antibiotics and found that infants who received antibiotics in their first week of life were at an increased risk of developing colic, but the results were on the borderline of statistical significance.

Additionally, there was a clear association between when the first antibiotic course was received, the number of antibiotic courses received, and the type of antibiotic received (how broad they were).

Discussion – Some of the results and analysis demonstrated were similar to other, smaller studies that discussed asthma and allergy for example. However, this study failed to show an association between antibiotic exposure and inflammatory bowel disease, especially Crohn’s disease, which has been demonstrated in previous studies. This could partly be explained by the fact that lots of different data that was collected from many different studies (which takes us back to the fact that these studies depend a lot on the factors that you search for and how you define them). However, a recent newer study did found an association between antibiotics prescription in children and the development of the inflammatory bowel diseases, read more here.
In addition to statistical bias, another limitation that needs to be taken into account is the possible predisposition of children with an inherent immune tendency to develop certain illnesses to also suffer from infections that require antibiotics, in which case the causality behind the association varies. Furthermore, there are diseases that obviously exist from birth but are only diagnosed later in life and so the association with exposure to antibiotics in these cases is irrelevant (for example, autism).
But what is my take home message from this meta-analysis, which does show a clear association between exposure and the development of different conditions?
When the administration of antibiotics is unnecessary, then it is really unnecessary. And when it is needed, then it is needed.
Also, most of the studies that were included in the analysis were of children who had an early exposure to antibiotics, in the first two years of their life. This is an ‘intense’ period when it comes to antibiotics and respiratory illnesses. Most of these illnesses do not require treatment with antibiotics because they are viral, and it is really important to choose when and who to prescribe antibiotics to carefully.

And I’m left to hope that those who need antibiotics will receive them and those that don’t will not. For that you need to be a good and skilled pediatrician and this website is full of content that can help guide you to an educated conversation with your pediatrician when it comes to decisions about treatment of both common and uncommon infectious illnesses (ear infections, respiratory infections, streptococcal throat infections, bacterial skin infections, salmonella, rhinosinusitis, animal bites, viral infections that do not need to be treated with antibiotics and other illnesses such as PFAPA, RSV infection and also some information about antibiotics themselves).

I’m a big believer in parents. And I truly believe that if parents know how to ask their pediatrician the right questions, their child will receive the treatment that is best for them.

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