UmbrelLACT Study: Clinical Lactation Study on the Exposure to Medicines Via Human Milk

Clinical Lactation Study on the Exposure to Medicines Via Human Milk: an Umbrella Study Protocol

The goal of this observational study is to determine the concentration of medicines in human milk during maternal medicine intake. The main questions it aims to answer are:

• What is the concentration of maternal medicines in human milk?
• What is the (estimated) intake and exposure in the breastfed infant?

Participants will be asked to

• fill out a questionnaire regarding medical data of the mother and child
• track medication intake for 3 days
• collect milk samples during 24 hours
• optionally, donate 2 blood samples of the mother and give consent to one blood sample of the child
• fill out a questionnaire regarding the general health of the child.

There is an immense information gap regarding safety of medicines during lactation which can result in a lack of breastfeeding adherence. According to literature, 50% of women need pharmacotherapy in the postpartum period. However, the proportion of nursing women in need of medication rises, due to later age pregnancies and the increased prevalence of chronic diseases. Evidence-based decisions on the use and selection of medicine during breastfeeding are challenging for many medicines, due to the lack of available information, such as cardiovascular compounds (e.g. atorvastatin, simvastatin), antidepressants (e.g. venlafaxine), anti-epileptics (e.g. topiramate, pregabalin), etc. This often results in unnecessary cessation of breastfeeding or poor adherence to/avoidance of pharmacological treatment.

The objective of this prospective trial is to collect information about the human milk transfer of maternal medicines, subsequent infant exposure, and general health outcome of the infant. Furthermore, the data of this clinical lactation study will be used to verify the performance of pharmacologically-based pharmacokinetic (PBPK) models to predict disposition of medicines in human milk and subsequent neonatal exposure during lactation. An umbrella protocol approach is used. This means that each request or compound for which milk samples might be collected / offered by women, will be reviewed and evaluated for feasibility and relevance.

The investigators expect to enroll 5, at maximum 15, mothers per year, who have been prescribed maternal medication for medical reasons and are breastfeeding their infant (/expressing milk) while taking this medication. The participating mother will be asked to collect milk samples and optionally to donate 2 blood samples during 24h: one at the time of milk pumping the first time after medication intake and one at the last pumping session of the 24h period. The parents can optionally consent for collecting a blood sample of the infant for the study (1-5% of the total blood volume, according to the FDA guidelines). In addition, clinical maternal and infant variables will be collected, as well as medication regimen, sampling details and general infant health information using 2 questionnaires.

To conclude, with this study data about the concentration of maternal medication in human milk, and the exposure in the nursing infant will be generated. This information is an essential first step towards evidence-based risk assessment on the use of drugs during lactation.

Inclusion Criteria:

• For breastfeeding women

  • Maternal age: ≥ 18 year
  • Currently exclusively or partially breastfeeding (/expressing milk) at the time of milk sampling
  • Using medicines for any indication, with at least 5 half-lives of the medicine taken
  • Willing to express and collect human milk
  • Signed informed consent to participate and for processing their personal data

• For infants

  • Gestational age at birth: ≥24 weeks
  • Parental signed informed consent to participate and for processing their personal data

Exclusion Criteria:

• Maternal age <18 years
• Mother of twins
• Not meeting the inclusion criteria