Early-Life Antibiotic Use and Dental Health Outcomes
In this podcast, Mihiri J. Silva, PhD, and Dharini Ravindra, DCD, discuss the results of their team's recent systematic review examining the relationship between antibiotic exposure in early childhood and adverse effects on dental caries, tooth staining, and developmental defects of enamel.
Additional resource:
- Ravindra D, Huang G, Hallett K, Burgner DP, Gwee A, Silva MJ. Antibiotic exposure and dental health: a systematic review. Pediatrics. 2023;152(1);e2023061350. doi:10.1542/peds.2023-061350.
Mihiri J. Silva, PhD, is a senior lecturer at the Melbourne Dental School at the University of Melbourne and a clinician scientist fellow and consultant pediatric dentist at the Murdoch Children's Research Institute and the Royal Children's Hospital in Melbourne, Australia.
Dharini Ravindra, DCD, is a pediatric dentist in private practice and a researcher at the Murdoch Children's Research Institute in Melbourne, Australia.
TRANSCRIPTION:
Leigh Precopio: Hello everyone and welcome to another installment of Podcasts360, your go-to resource for medical education and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360, a multidisciplinary medical information network.
Antibiotic use is continually on the rise, and the impact that antibiotic use may have on various health outcomes is of global concern.
To explore how the use of antibiotics in pediatric populations may lead to adverse effects on dental health, a multidisciplinary team of health care practitioners conducted a systematic review of the literature to examine the relationship between antibiotic exposure before 8 years of age and dental caries, tooth staining, and developmental enamel defects.
We are joined by the lead study authors, Mihiri J. Silva, PhD, and Dharini Ravindra, DCD, to delve deeper on the topic of antibiotics and dental health. Dr Silva is a senior lecturer at the Melbourne Dental School at the University of Melbourne and a clinician scientist fellow and consultant pediatric dentist at the Murdoch Children’s Research Institute and the Royal Children’s Hospital in Melbourne. Dr Ravindra is a pediatric dentist in private practice and a researcher at the Murdoch Children’s Research Institute.
Thanks so much for taking the time to speak with me today. To begin, could you discuss what prompted this study? Why now?
Mihiri J. Silva, PhD: Yeah. As I mentioned, I work at the Murdoch Children's Research Institute, and we are a pediatric research institute co-located with a tertiary pediatric hospital in Melbourne. And so we have a fairly big dental department and this means that we sort of have these opportunities to interact quite a bit with our medical colleagues. And Amanda Gwee, PhD, who's one of the other co-authors of this publication, and I got talking about tetracyclines, in particular the newer formulations of tetracyclines and the hesitancy amongst clinicians to prescribe it when it was perhaps the right drug for the patient because of their concerns about adverse effects on dental health. Particularly tooth staining and discoloration. And I think that's sort of, you know, a lot of the public also have concerns that if they have antibiotics just generally in childhood that they might have problems with their teeth. And Amanda had done some work previously in this area and was interested in sort of, leading a further study. And so that was the origins. But I think Dharini might wanna speak to a little bit about, I guess, what we know about antibiotic use and how prevalent it is from Australia and globally as well.
Dharini Ravindra, DCD: Yeah, I think the, that second part of the reason why this study happened now is, obviously we've had a significant increase in antibiotic use. I mean, within Australia that is more than 200% but globally it's like one in five kids these days have had at least one antibiotic in childhood. So I think knowing the prevalence of antibiotic use today, knowing the effects of these drugs, and there hasn't been a study like this before, so I think one of the main reasons why we decided to do this.
Leigh Precopio: Could you briefly discuss some of the key takeaways from your review?
Dr Ravindra: Mostly I think the key takeaway that we took is that based on the results that we shouldn't really be thinking about dental staining as a reason not to prescribe antibiotics for kids when it's the most appropriate antibiotic to be used in a clinical setting. Basically that the dental effects shouldn't minimize appropriate antibiotic use because the dental effects aren't as, severe I guess, as we had previously thought, especially with newer formulations of tetracyclines like doxycycline. The review showed that there was if any evidence basically that doxycycline would cause staining in early childhood. So I guess that not limiting antibiotic use based on the dental effects is the key takeaway from this one. Mihiri, did you have anything to add?
Dr Silva: Yeah, I think, you know, there've obviously been changes to guidelines about this but there is still a hesitancy, as I said, amongst clinicians because of concerns about staining particularly. But we looked at a range of adverse effects including tooth decay and sort of developmental problems with tooth structures, particularly the enamel. And overall, we felt that there was no evidence to support any reason to avoid the current formulations, particularly at the dosages that are currently used. So I think that's the key takeaway.
Leigh Precopio:The results of your review found that there was no evidence of adverse effects on dental health with newer tetracycline formulations and that there were inconsistent results regarding antibiotic use and enamel defects or dental caries. Are these results that surprised you? Why or why not?
Dr Silva: They didn't really surprise us. I think they will surprise a lot of people though because... And this is really what led to us, I suppose, starting this study because we, you know, As I mentioned, the guidelines have changed and we do feel that this concern about adverse effects is probably unnecessary. And so in some ways, I guess, we weren't surprised but I know just even talking to our colleagues, even our dental colleagues, you know, there's certainly, people are quite surprised to hear such fairly strong conclusions about the lack of evidence about adverse effects.
I think the other outcomes that we looked at, they're quite different. Particularly tooth decay. Tooth decay is something that's essentially caused by the oral microbiome losing its balance because of exposure particularly to sugars. But it's a sort of really complex, multifactorial condition with lots and lots of different factors that ultimately influence whether an individual develops a mouthful of tooth decay or not. And so the role of say antibiotics in that is less clear, and I think that's what we expected to find. We think that we need more evidence in this area, but it is such a complex condition and overwhelmingly say things like sugars, toothbrushing, exposure to fluoride, are the most important determinants of tooth decay. Enamel defects is an interesting one because it is a developmental condition that occurs as a result of disturbance to tooth formation early in life. So it was interesting to explore that. But again, they too can be quite complex and the process of tooth development, whilst it's genetically controlled, is really susceptible to lots of different environmental influences. And so again, we didn't see a strong response. Dharini do you wanna talk a little bit more about the enamel defect?
Dr Ravindra: Yeah, with enamel defects, I think it's relationships that have been explored, like the relationship between antibiotics and enamel defects has been explored in quite a bit of detail in previous studies. I think knowing that the evidence base from those studies is inconclusive. I think a lot of the problems with enamel defects is that it's hard to separate out whether the disease process or whether the antibiotic itself is interfering with tooth formation. And this study isn't going to be able to do that either. So I think obviously in children it is paramount to treat the disease, but we'll never be able to separate whether it's the disease or the antibiotic that is interfering with that tooth calcification process.
I do think the most surprising thing perhaps from the whole study is the high quality of evidence regarding the newer tetracycline formulations. There is quite a lot of really, really good quality evidence about doxycycline and its lack of staining. And I think people, well I guess we were definitely surprised about how much evidence is out there. I guess it hasn't really been brought together before and the amount of evidence and the quality of the evidence regarding doxycycline and its lack of tooth staining is quite good and prominent.
Dr Silva: I might just go back as well to enamel defects because it's sort of - only because I think sometimes people, particularly medical practitioners, might not be aware of what we mean by enamel defects and they are quite, enamel defects are quite varied in how they appear in the mouth. And they can have different causes. Tooth formation happens either in utero or very early in life, but it is, the stage of tooth development kind of varies depending on the tooth and the age. And essentially these enamel defects can look like pits or sort of areas of tooth structure that didn't form, so grooves, pitting, or abnormal shapes of teeth. Or it can be differences in appearance. So teeth can have kind of white marks or yellow marks. They can be qualitative or they can be quantitative. So it might be that there wasn't enough tooth structure formed like in groups and pits, or it might be that the tooth structure is formed in the right shape but it is weak. And so when it's, you know, doing what teeth do chewing and biting and all of those things and exposed to the oral environment those teeth break down quite rapidly. So it is kind of very broad when we say enamel defects, and we did look at sort of some specific, you know, conditions which are probably more common in the population than other types of enamel defects.
Leigh Precopio: How might the results of this review impact clinical practice?
Dr Ravindra: I guess the main takeaway here is that it's adding to the body of evidence that surrounds the use of, or supports the use rather, of doxycycline in children less than 8 years old. I think there have been a few studies floating around over the last few years but this review brings them all together. But it also adds and echoes those newer prescribing guidelines from the AAP red book which was published I think in 2021, the latest edition, which states that it's safe to use doxycycline for up to 21 days in children less than 8 years of age without any concern. So I think this obviously has implications in terms of antibiotic use, but also antimicrobial stewardship in that using the right antibiotic at the right time for the right reasons should be paramount regardless of any supposed effects. But I think we can now, especially with doxycycline, quantitatively say that there are no dental effects that we need to worry about. So I think there is definitely a clear impact for clinical practice. I think people will be surprised so I don't know how quickly clinical practice will change but it's good evidence and so it's definitely something to think about.
Leigh Precopio:What are the next steps for research concerning the impact of antibiotic use on dental health?
Dr Silva: Yeah, we have thought about this because it's really nice, obviously, to be able to demonstrate with some robust evidence about, you know, some elements of the research questions that we were trying to answer. But then of course there's obviously opportunities and further things that need to be explored. One might be, I guess, as the of antibiotics changes and how variations to say dosages, or how that might affect dental outcomes, whether we are talking about less so tooth staining I suspect, but those other conditions that we talked about, tooth decay and enamel defects as well. And I think Dharini you were going to make a point about, I think one of the big questions and, particularly in thinking about these kinds of observational studies, is trying to understand that dose-response relationship better because that's, you know that's how we use these medications. And so these overarching kind of statements are sometimes not as helpful as knowing that dose-response relationship and knowing when something might be more likely to cause a problem. Dharini, did you wanna expand on that?
Dr Ravindra: Yeah, I guess this current study that we've done definitely draws a lot on observational data which is great, but obviously it would be better enhanced if we could have dose-response relationships where you could see a specific effect from a dosage for that particular drug. I guess looking in an ideal situation, longitudinal cohort studies with dose-response relationships using antibiotics would be a really good way to quantify this relationship further. Whether or not that's ethically possible, is a different question. The data that we do use in this study is largely observational, but that's all the research that's out there. But yeah, a dose-response relationship would be able to quantify the relationship between antibiotics and dental effects.
I think the other thing that we were talking about, Mihiri, is definitely I think what you touched on earlier, is enamel defects or caries especially has quite a strong relationship to the oral microbiome and whether or not antibiotics cause a direct effect or they're causing an indirect effect on that oral microbiome to cause these effects would be an interesting avenue to look through in the future. Whether that includes like microbiome analysis or biological sampling combined with these dose-response relationships, that would be another nice way to quantify exactly the process that's by which this is happening. So I guess that's for the future.
Dr Silva: Yeah, I was going to agree with you on that one Dharini, because I think when we talk about something like tooth decay which is just really prevalent and burdensome around the world, and then, you know, this increasing sort of use of antibiotics around the world as well. Whilst we know that things like sugar and toothbrushing are important and are probably the key determinants of tooth decay, we also need to understand these influences and how they might sort of, particularly as we move towards more personalized medicine and understanding individual patients' susceptibility. And particularly when we're talking about perhaps children who spend more time in hospital or who have more significant medical conditions, you know, the impacts on them may be different to the general population. It would be great to see more dental outcomes being sort of included in these larger studies, where you are looking at these sort of long observational studies but interventional studies as well that sort of consider the impact on the oral microbiome and dental health as well.
Leigh Precopio: Is there anything else you would like to add today?
Dr Silva: I think one of the real strengths of this project was we had you know, infectious diseases specialists working with sort of pediatric dentistry and Amanda has a sort of pharmacology background as well, and bringing that expertise together. And I think sometimes, particularly when we're talking about these kinds of real world problems, they often need multidisciplinary teams and those perspectives. I mean, certainly from a pediatric dental perspective, we learned a lot and I think our medical colleagues learn a lot in terms of the dental issues and how they work. And I think that dialogue across disciplines is really important and we know it's important in clinical practice when we're caring for these patients, but also in research settings as well. So yeah, I think it's great to see this being, sort of equally interesting to dental and medical audiences because of the overlap across the two areas.
Leigh Precopio:Thank you again for taking the time to answer my questions.
Dr Ravindra and Dr Silva: Thanks very much for having us.