Cetirizine is a medicine that is used to prevent and treat allergy symptoms, such as red, itchy eyes, sneezing, a runny or stuffy nose, or hives. This medicine is recommended for breastfeeding women, which makes it important to study how much of the drug transfers to mother’s milk. The ConcePTION project has developed a new pharmacokinetic (popPK) model to predict the concentrations of cetirizine in human breast milk, and to estimate how much of the medicine that is received by the breastfed infant.

The results are published in the journal Basic & Clinical Pharmacology and Toxicology. According to the authors, the concentration of cetirizine in milk was low in relation to the amount of medicine taken by the breastfeeding mother. Which means that the amount of medicine that the breastfeeding baby would ingest is small compared to the mother’s dose. The concentration in milk is also affected by the length of the feeding, or (as in this study) how long it takes to pump or express milk. “Shorter pumping durations lead to higher concentrations, potentially due to changes in milk compositions over time”, says Erik Melander, researcher at the Department of Pharmacy at Uppsala University, and one of the authors of the study.

The results are reassuring for mothers that need to treat their allergies while breastfeeding. According to the authors, the results support the current recommendation that cetirizine is compatible with breastfeeding. “The findings could help improve clinical guidelines and inform product labels, providing clarity for healthcare providers and breastfeeding mothers,” says Erik Melander.

Do you want to know more? Read the article: Melander E, Nielsen EI, Lindqvist A, et al. Population pharmacokinetic modelling of cetirizine concentrations in human breast milk—A contribution from the ConcePTION project. Basic Clin Pharmacol Toxicol. 2024; 1-9. DOI: 10.1111/bcpt.14100

This week, ConcePTION is taking part in the #MedSafetyWeek social media campaign together with 107 organisations from 94 countries, to raise awareness of preventing side effects of medicine. Because sometimes pregnant women need to take medicines. And during pregnancy, some effects cannot be assessed until after the child is born. Therefore, it is important that pregnant women report their medicine use regardless of their immediate effects.

Medicines are used by millions of people to treat their illness. However, sometimes medicines can cause side effects. The theme of this year’s #MedSafetyWeek campaign is preventing side effects. By using medicines correctly, you can drastically reduce the risk of side effects and severe harm. And generally, by reporting side effects when they occur, you can help make medicines safer for everyone. But when you are pregnant, it is important to report the medicines you use regardless of whether you experience immediate side effects or not. That is because some effects, and side effects, cannot be assessed until after birth.

One objective of the ConcePTION project is to increase the volume, quality, and comprehensiveness of reports on the use to different medicines in pregnancy and breastfeeding. There are several ways to report medicine use during pregnancy, depending on which country you live in. The different registries are interested in what is often called exposures (when you used a particular medicine). When you report the medicines you take during your pregnancy, you help bridging the knowledge gap in medicine safety during pregnancy – and contribute to safer medicine use for pregnant women in the future. Every report counts!

One of the outcomes of our effort is a mobile application developed for the UK market, called Meds4Mums2B. Trough the app, women in the United Kingdom will be able to both report the medicines they have used during pregnancy and breastfeeding and receive information on medicine safety through the app. By using the app, women and healthcare providers in the UK can help future mothers, by providing information about how their children develop.

The app can only handle information from the UK. The reason for this is the fact that different countries have different systems for collecting data for pharmacovigilance in pregnancy and breastfeeding. If you are not living in Great Britain or Northern Ireland, and have used medicines during pregnancy and breastfeeding, you can report to the company that makes the medicine (the Marketing Authorization Holder), or your doctor. In some European countries, there are also specialised, country-specific centres called Teratology Information Services. There is also the equivalent of the UK MHRA in every country that can receive your report.

Want to know more about how to report? Go to our dedicated web page on how to report medicine use in pregnancy and breastfeeding.

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For ethical reasons, pregnant and breastfeeding women are rarely included in clinical trials. To close the knowledge gap regarding the safety of medicine use during pregnancy and breastfeeding, researchers rely on other sources of information. One of them is electronic healthcare data – sometimes referred to as Real World Data. These data are crucial for understanding health events in populations and making decisions in public health and regulation. A paper recently published in American Journal of Epidemiology suggests a method to improve the validity of studying health events in populations using Real World Data.

In database studies, different algorithms are used to measure the occurrence of events, like the occurrence of a disease or a negative effect of an exposure to a medicine in utero. But algorithms are not hard facts and are subject to errors, both false positives and false negatives. Validity indices like sensitivity, specificity, and positive predictive value (PPV) help measure these errors. Guidelines recommend estimating these indices to correct observed rates. The authors of a publication in the American Journal of Epidemiology propose using a screening algorithm on top of the chosen algorithm, and provide a way to test and correct biases in the study results.

Validation studies are often impractical due to cost, time, or ethical reasons. Estimating sensitivity is challenging due to the rarity of events, leading to underestimation of number of events and risk of occurrence of events. Moreover, misclassification of outcome algorithms can introduce bias in risk ratio and risk difference in studies of association.

The authors suggest using an auxiliary screening algorithm alongside the primary one. The primary algorithm should have high positive predictive value, and the screening one should capture additional cases. Estimating positive predictive value for both indicators allow to reduce bias and, if stratified by exposure groups, to test for differential misclassification and reduce bias in measures of association.

“We suggest a method to improve the validity of identifying health events in populations using electronic health data, especially when dealing with algorithms that might have errors. This will be important not only for studies on medicine safety for pregnancy and lactation but also for other epidemiological studies and will mitigate the impact of misclassification on study results,” says Rosa Gini, co-lead of ConcePTION WP7 and Head of the Pharmacoepidemiology Unit of ARS Toscana, Italy.

Do you want to know more? Read the study: Limoncella G, Grilli L, Dreassi E, Rampichini C, Platt R, Gini R. Addressing bias due to measurement error of an outcome with unknown sensitivity in database epidemiological studies. AJE, 2024. DOI: https://doi.org/10.1093/aje/kwae423

By Anna Holm Bodin & Märta Karlén