A new paper from Swansea University in collaboration with ConcePTION has called for breastfeeding data to be routinely collected in healthcare databases so that the long-term impacts of medicines taken by women during pregnancy and when breastfeeding, can be better understood.

In the paper, which has been published in the International Breastfeeding Journal researchers argue that the lack of data collection on breastfeeding represents a significant ‘blind spot’ leading to an ‘information desert’ in understanding the impact that taking medicines during and after pregnancy, has on breastfeeding rates and long-term infant development.

Researchers recommend that it should now be a priority that data on breastfeeding and medicines used by women during and after pregnancy and in labour are included in population databases along with data on subsequent child neurodevelopment, so that meaningful research can take place into the benefits and harms of medicines.

The authors report that population databases should link data on three factors: medicine exposure; breastfeeding and infant development. It notes that across Europe, few population databases hold data on all three together, and there is little uniformity in outcomes, definitions, methods and timing of assessments.

Professor Sue Jordan of the university’s Faculty of Medicine, Health and Life Science, who led the research said: “Currently there is poorly standardised recording of breastfeeding in most population databases and it is this that hampers analysis and understanding of the complex relationships between medicine, pregnancy, breastfeeding and infant and maternal health.

Professor Christine Damase-Michel, Pharmacologist at the Faculty of Medicine and University Hospital of Toulouse (INSERM CERPOP) said:

“There is an urgent need to have high-quality linked data on medicines, long term childhood outcomes and modifiable risk factors, including breastfeeding so that robust analyses of medicine-related benefits and harms can take place, which will ultimately allow women to take informed decisions when making choices on their own medical treatment, and breastfeeding.”

The paper was published in International Breastfeeding Journal: Jordan, S., Bromley, R., Damase-Michel, C. et al. Breastfeeding, pregnancy, medicines, neurodevelopment, and population databases: the information desert. Int Breastfeed J 17, 55 (2022). https://doi.org/10.1186/s13006-022-00494-5

This text is based on a press-release from Swansea University. Read more about how Swansea University is helping to improve medicine safety in early motherhood.

Seasonal allergies, diabetes and post-partum depression affect breastfeeding women worldwide. But there is very little information available about the transfer of drugs to breast milk and infants. Women who are breastfeeding are rarely included in clinical trials, but they still deserve to know if their medicines are safe. ConcePTION researchers recently published a paper in the Journal of Chromatography B that describes two developed and validated methods to determine how much of a drug the mother takes also transfers to her breastmilk, and potentially to her infant.

“We have established a method for quantifying the transfer of cetirizine, a drug commonly used by breastfeeding women for allergic conditions, in breastmilk, and venlafaxine and its active metabolite o‑desmethylvenlafaxine, a common antidepressant drug used during breastfeeding,” says Christine Wegler, who were part of a team of researchers from the Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP), Uppsala University, responsible for the analysis.

The authors also developed a method for quantification of the blood sugar-lowering agent metformin, used for the treatment of preexisting type 2 diabetes and gestational diabetes (where a pregnant woman develops the condition) in breastmilk and blood plasma. According to the authors, this enables the measurement of how much metformin is present in the infant’s bloodstream. And as a result, the determination of how metformin transfers to breastmilk.

The methods are made for high-throughput analysis, which enables the analysis of dozens, hundreds or even several hundreds of samples per day, with simple sample preparation for minimal loss of drug compounds, and rapid analysis. In total, it takes less than 3 minutes per sample. The minimal sample volume needed is 40 µL (microliters).

“This means, for example, that very small volumes of blood are required to determine the metformin level in the infant’s bloodstream. The methods are also highly sensitive and can measure at least 100 times lower levels than what have been possible with previous methods in the bloodstream after drug use. We are talking concentrations down to 0.65 µg/L [micrograms per litre],” Christine Wegler concludes.

With more knowledge, women can make informed decisions about whether or not to treat their health conditions. According to the authors, their work is contributing to the knowledge base on medicine safety in breastfeeding that is so desperately needed.

By Anna Holm

Read the paper: Wegler C, Saleh A, Lindqvist A, Nordeng H, Smeraglia J, Baranczewski B, Simple and rapid quantification of cetirizine, venlafaxine, and O-desmethylvenlafaxine in human breast milk, and metformin in human milk and plasma with UHPLC-MS/MS, Journal of Chromatography B, 2022;1205:123340, https://doi.org/10.1016/j.jchromb.2022.123340.

Pregnancy is usually not recommended for women suffering from pulmonary arterial hypertension (PAH), a condition characterised by high blood pressure in the lung arteries, because of the high maternal mortality rate. For this reason, there is little to no information about whether or not the medicines these women use are safe during pregnancy and breastfeeding. A recent ConcePTION case report follows and presents the clinical and pharmacokinetic (PK) data of one breastfeeding mother living with PAH and her infant, who were both exposed to medicines used to treat the condition, bosentan and sildenafil, when the infant was 21 months old.

“Before our contribution, there was one case study describing the use of both sildenafil and bosentan during pregnancy and breastfeeding with a ‘good outcome’. But the details, about for example what the dosage was and whether that dosage regimen could be linked to higher or lower levels of drug concentrations in the breastmilk, was limited. We found one study that measured sildenafil concentration in breastmilk. However, for bosentan, information about the transfer of the drug into breastmilk was completely lacking,” says Nina Nauwelaerts, PhD student at KU Leuven and one of the authors of the case report that was recently published in Frontiers in Pharmacology.

Researchers at KU Leuven, University Hospitals UZ Leuven, BioNotus and the Netherlands’ Pharmacovigilance Centre, Lareb, specifically investigated the case of one woman treated for PAH who also breastfed her infant. At the time samples were collected, the infant was 21 months old. The research team developed a bioanalytical method that allowed them to measure, or as the researchers say quantify, the concentration of both sildenafil and bosentan in the mother’s breastmilk. Based on calculating relevant parameters, they were then able to produce an estimate for what extent the baby was exposed to the drugs through the mother’s milk.

The results can be used to optimise future PK models predicting drug exposure through human breastmilk. To say for certain whether the medicines are safe to use during breastfeeding requires more than a single case report. Based on the researchers’ calculations, the infant was exposed to very low levels of both bosentan and sildenafil through the breastmilk. But although the researchers tried to provide some estimations, they also state that it is important to remember that the results cannot be directly translated to younger infants or babies that are exclusively breastfed.

“Likely there are metabolic and physiological features that differ from woman to woman, and variations in dosage and for how long and during what period a mother decides to breastfeed. This can also result in higher or lower levels of the drug in her breastmilk. We will continue our work to develop innovative models that can help us assess the risks of using these medicines during pregnancy and breastfeeding,” Nina Nauwelaerts concludes.

Read the article in full: Nauwelaerts N, Ceulemans M, Deferm N et al, Case Report: Bosentan and Sildenafil Exposure in Human Milk A contribution from the ConcePTION project, Frontiers in Pharmacology, 2022, vol 13, first online 15 June 2022

By Anna Holm