News items Medication for children not always evidence-based

7 March 2023

About two million children are prescribed medications every year, while effectiveness and safety are not always well researched. Innovative methods are therefore needed to properly substantiate the prescription of medications to children as well. This emerges from doctoral research by Nori Smeets of Radboud university medical center. 

The effect and safety of about half of all drugs administered to children have not been studied, or have been studied only partially. Often there is off-label drug use. This means that the drug is used for a different indication, different age or different method of administration than it is registered for. As a result, the amount of information on the use of a drug in children is limited and a formal benefit-risk analysis has not been performed. 

The journey of the drug through the body of children may be different than in adults. This creates differences in exposure and can cause treatment failure or lead to a potentially harmful overdose. Physician-researcher and PhD candidate Nori Smeets explains: 'Doctors regularly prescribe drugs for children based on experience alone, especially in the youngest children.' 

However, it is neither logistically nor financially feasible to study every drug for every age group in the traditional way. The researchers showed that studies of drug concentration in the blood - pharmacokinetic studies - are often available. These studies help determine an effective and safe dose. After all, if you know exactly how the body handles the drug, you also know how this affects the concentration in the blood.

How do the kidneys work?

Because kidney function can also largely determine the amount of drug in the blood, we looked specifically at this in newborn babies, explains Smeets. She examined the kidney function of almost a thousand healthy babies from fifty international studies and combined all these data into an age-based measure of kidney function during the first month of life. She found a large increase in kidney function during the first week. She explains: "We saw that the kidney function of newborn babies doubles in the first five days after birth. After that, kidney function continues to rise gradually until the child reaches the age of two years. Then the kidneys work as well as those of an adult, adjusted for body size.'

To properly estimate babies' kidney function during hospitalization, the researchers proposed a new calculation. The calculation, based on creatinine, was tested in a group of nearly 50 babies who were admitted to Radboudumc Amalia Children's Hospital. With this, the researchers proved that the proposed calculation works very well. Smeets: 'I am pleased that we have been able to demonstrate that our calculation is correct. As far as we are concerned, we have now laid the foundation for better estimation of the kidney function of newborns.'

With this, a better dose of a medication can be given, because it is now known how well the kidneys can excrete the medication. By predicting, based on pharmacokinetics, how a drug is absorbed by a body, better doses can be given to children.

More information about this PhD defense

PhD Defense on March 7 at 2.30 pm by Nori Smeets. Title dissertation: Paediatric pharmacology: small but mighty. On evidence, elimination and enalapril (available online after March 7). (Co-)promoters: Prof. Dr. Saskia N. de Wildt and Prof. Dr. Michiel F. Schreuder. Watch the defense here.

More information

Pauline Dekhuijzen

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