Women often use medicines while breastfeeding, but we have very little information on how the mother’s medicines affect the breastfed infant. Researchers in the ConcePTION project have developed a generic work flow for predicting medicine concentrations in breast milk using physiologically-based pharmacokinetic (PBPK) modelling, just published in Pharmaceutics.

The prediction is done using computational model, an “in silico” tool that allows the assessment of drug exposure for a given dosing regimen. The team studied the performance of a generic physiologically-based pharmacokinetic (or PBPK) model to predict concentrations in human milk for ten medicines that are different on a physiochemical level. According to Nina Nauwelaerts and Julia Macente, PhD students at KU Leuven and lead authors, the medicines were selected because they have different elimination pathways, where they are taken care of by different enzymes involved in our metabolism, or the kidneys.

The team was able to predict the pharmacokinetic profile in breast milk, which means that we are able to predict how much of the medicine is present in the milk at different time points after the mother took the medicine, and how much of a substance crosses over to the mother’s millk. This makes it possible to estimate, or calculate, how much of the medicine the infant will receive through breastfeeding. Knowing more about the ‘pharmacokinetic behaviour’ in human milk will allows us to predict how much of a substance infants will be exposed to. The team managed to make this prediction for eight of the ten medicines: amoxicillin, cetirizine, caffeine, levetiracetam, metformin, sertraline, valproic acid and zidovudine.

For the other two drugs, nevirapine and tenofovir, the model overpredicted the concentration in milk. According to Nina Nauwelaerts, from a safety perspective, it is reassuring that the model never underpredicted the exposure to the medicine via breastfeeding.

“What is important to note is that the ‘dose’ that an infant could receive via breast milk that the model calculated were low for all medicines. Also when we compare that dose to what infants are prescribed when they need to be treated themselves”, says Nina Nauwelaerts.

The framework that this model has established here is an important step from where we are today. The PBPK models brings us closer to evidence-based safety assessments of the medicines that mothers receive, already in the early stages of drug development. Using this model makes it possible to develop quantitative information on how infants can be exposed to mothers’ medicines, before we are able to generate any clinical data.

Want to read the paper? It is published Open Access in Phramaeutics: Nauwelaerts N, Macente J, Deferm N, Bonan RH, Huang M-C, Van Neste M, Bibi D, Badee J, Martins FS, Smits A, Allegaert K, Bouillon T, Annaert P. Generic Workflow to Predict Medicine Concentrations in Human Milk Using Physiologically-Based Pharmacokinetic (PBPK) Modelling—A Contribution from the ConcePTION Project. Pharmaceutics. 2023; 15(5):1469. https://doi.org/10.3390/pharmaceutics15051469

By Josepine Fernow

Real-world data often refers to data generated by routine healthcare delivery, including electronic health records and claims data, or through patient-generated sources such as wearable devices, social media, and mobile apps. Real-world data has the potential to transform healthcare by enabling more personalized, evidence-based care, while improving health outcomes, and reducing costs. Nonetheless, it also presents challenges around data quality, privacy, and bias, which must be addressed to ensure the quality of the studies.

On 20 April 2023, we organised a webinar on using real word data for research on medication safety during pregnancy and breastfeeding. During the webinar, Miriam Sturkenboom & Marieke Hollestele from University Medical Center Utrecht, the Netherlands, Rosa Gini from Agenzia regionale di sanita della Toscana, Italy and Vjola Hoxhaj from University Medical Center Utrecht, the Netherlands discussed the opportunities and challenges of using real-world data to investigate the safety of medications during pregnancy and breastfeeding.

Want to learn more about the latest contributions of ConcePTION in this field and how studies using real-world data can inform clinical and regulatory decision-making to ultimately improve the health of both pregnant women and their children? The presentations were recorded and a playlist is available to watch on the ConcePTION project’s YouTube channel.

The webinar started with an introduction by Professor. Miriam Sturkenboom from the University Medical Center Utrecht in the Netherlands, who presented on how the ConcePTION project is generating evidence on medicine safety in pregnancy.

The second presentation was from Marieke Hollestele, PhD student in bioethics from University Medical Centre Utrecht, the Netherlands, who talked about how ConcePTION is using real world data in an ethical responsible way.

In the third presentation, Vjola Hoxhaj from University Medical Center Utrecht, the Netherlands, presented on how we assess quality in real world data.

In the last presentation of the day, Dr. Rosa Gini from Agenzia regionale di sanita della, Toscana, Italy, talked about how to identify and characterize pregnancies from heterogeneous real-world data sources.

By Josepine Fernow

Where can we find data that links infant outcomes, breastfeeding and medicine exposure? A new systematic scoping review from ConcePTION shows that the information that is available is not enough. And calls for action to provide long term population-based data and to monitor infants for adverse effects.

Information on the impact of medicines on breastfeeding rates and the health of breastfed infants remains scarce. Researchers from Swansea University led the work on a systematic scoping review just published in PLOS ONE, aiming to identify existing databases and cohorts with information, in this field where information and evidence are scarce.

Professor Sue Jordan from Swansea University’s Faculty of Medicine, Health and Life Science, led the research. She indicated that some of the existing resources, such as LactMed, are excellent. But despite thorough searches, they often have little information to offer and report only small case series. This puts new mothers and their babies in a difficult position when it comes to decisions about medicines – that the mother needs – and breastfeeding, which has health benefits for both mother and baby. Sue Jordan said:

“No sections of the population should be excluded from the protection afforded by timely collection and analysis of data on the safety of medicinal products.  However, the omission of breastfeeding data from most population databases indicates that there are few data to inform breastfeeding patients and those intending to breastfeed”.

In the paper, the authors ask the research community and health authorities to action this problem, and provide long-term population-based data on any adverse events in infants exposed to medicines through breastmilk.

We also need more data on whether the need for treatment or the medicines themselves lead to any reductions in breastfeeding rates. And, the authors emphasise, that in order to ensure that the impact of ‘not breastfeeding’ is captured, long-term data needs to include educational outcomes for the child.

More data are needed on newborns. Authors call for infants to be monitored for any possible adverse drug reactions from exposure to medicines through breastmilk, even if problems can be rare, subtle and easily overlooked. If the mother needs medicines to treat mental health conditions, we should observe the infant for sleepiness, drowsiness and sedation. We should also weigh and chart sleep more closely than is done in the standard psychical assessments, which, in the UK, are done at 72 hours and 6 weeks.

New mothers are a vulnerable group, and some struggle with breastfeeding. Knowledge about medicines that could make breastfeeding more difficult, or complicate the decision to breastfeed, requires us to provide more support to these patients, and address any fears of unknown adverse effects of medicines on their child.

Read the paper: Where are the data linking infant outcomes, breastfeeding and medicine exposure? A systematic scoping review

Cite as: Jordan S, Komninou S, Lopez Leon S (2023) Where are the data linking infant outcomes, breastfeeding and medicine exposure? A systematic scoping review. PLOS ONE 18(4): e0284128. https://doi.org/10.1371/journal.pone.0284128

Want to know more? Read the press-release from Swansea University: Action needed on breastfeeding data collection to gauge medicine impact

By Josepine Fernow