Pragmatic and Contextualized Methods Selection for Safety Assessment of Infant Systemic Exposure Through Human Milk: The Milk4baby Decision Tree Approach – A Contribution from the ConcePTION Project

This decision tree was developed by members of the Swiss Teratology Information Service, who are responsible for the content of this webpage. Details about the development and scientific evaluation of the decision aids below are provided in a scientific journal research article.

Disclaimer: This tool is provided for informational and educational purposes and should not be used as a substitute for professional medical judgement. Users of the decision aids below are encouraged to make decisions about the use of medication by breastfeeding women whilst also using their own knowledge, experience and evaluation of the clinical scenario. Breastfeeding women are encouraged to speak to a healthcare professional before making decisions about using medicines whilst breastfeeding. The developers of these decision aids and ENTIS assume no responsibility for any clinical decisions or outcomes resulting from their use.

The Milk4Baby Decision Tree

The Milk4Baby decision tree was developed as a roadmap to inform the decisions of regulators, manufacturers, researchers and healthcare providers in the design and/or interpretation of future milk studies. Figure 1 illustrates how to use this decision tree.

Figure 1. Overview of the Milk4Baby decision tree

Evaluation 1: Expected prevalence of medication utilization in the childbearing population

Figure 2: Evaluation of the expected prevalence of utilization in the childbearing population

Evaluation 2: Medication safety profile

Figure 3: Evaluation of the medication safety profile in infants

Interactive evaluation of the medication safety profile in infants

Is the medication safety understood in infants below 2 months, 6 months or 2 years of age?YesNo

Is the medication considered safe, moderately safe or unsafe?SafeModerately safeUnsafe

Is the medication safety understood in children below 12 years of age, or in adults?YesNo

Is the medication considered safe, moderately safe or unsafe?SafeModerately safeUnsafe

Result

Low Risk

Result

Intermediate Risk

Result

High Risk

Clear the form to start over

Evaluation 3: Level of medication exposure in infants

Figure 4: Evaluation of the infant medication level of exposure

Low bioavailability = 0 to 30%, intermediate bioavailability = 30 to 70% and high bioavailability= 70 to 100%

Interactive evaluation of the infant medication level of exposure

Does the medication undergo systemic absorption in the mother, reaching therapeutic concentrationsYesNo

Is the medication likely to transfer in high amounts into human milk?YesNo

What is the oral bioavailability of the medication in infants?LowIntermediateHighUnknown

Is there a risk of accumulation?YesNo

Is there a risk of accumulation?YesNo

Is there a risk of accumulation?YesNo

How often is the medication utilized?Intermittent and chronic short termChronic long term

Result

Low Risk

Result

Low Risk

Result

Intermediate Risk

Result

High Risk

What is the oral absorption of the medication in adults?LowIntermediateHighUnknown

Is there a risk of accumulation?YesNo

Is there a risk of accumulation?YesNo

How often is the medication utilized?Intermittent and chronic short termChronic long term

is the medication likely to be bioavailable in infants?YesNo

Is there a risk of accumulation?YesNo

How often is the medication utilized?Intermittent and chronic short termChronic long term

Result

Low Risk

Result

Intermediate Risk

Result

High Risk

What is the oral bioavailability of the medication in infants?LowIntermediateHighUnknown

Is there a risk of accumulation?YesNo

Is there a risk of accumulation?YesNo

Result

Low Risk

Result

Intermediate Risk

Result

High Risk

What is the oral absorption of the medication in adults?LowIntermediateHighUnknown

Is there a risk of accumulation?YesNo

is the medication likely to be bioavailable in infants?YesNo

Result

Intermediate Risk

Result

High Risk

Clear the form to start over

Methodological approach selection

Figure 5A: Decision tree for low expected prevalence of utilization

Figure 5B: Decision tree for intermediate expected prevalence of utilization

Figure 5C: Decision tree for high expected prevalence of utilization