Monitoring the development of breast tissue composition during pregnancy, lactation and involution

Breastfeeding offers many benefits for mothers and children. Unfortunately, not
every mother who wants to breastfeed, has the opportunity to feed her child
herself. One of the most common reasons to stop breastfeeding is (the
perception of) too little milk production, this is called lactation
insufficiency. Until now, little is known about how breast development during
pregnancy and lactation influences milk production and breastfeeding duration.
In addition, little is known about the changes in human breast anatomy during
pregnancy, lactation and - in particular - post-lactational involution.
(Changes in) breast tissue composition during these periods affect the
visualization of malignant lesions and may also affect the pharmacokinetics of
chemotherapeutic agents. Also, an increasing amount of evidence indicates that
the process of post-lactational involution in rodents is potentially related to
the development of breast cancer. Therefore, more fundamental insight into
human breast development during pregnancy, lactation and involution is of
utmost importance.

The aim of the study is to map the changes that occur in breast tissue
composition during pregnancy, lactation and post-lactational involution. The
secondary aims are to:
• validate the performance of diffuse optical spectroscopic imaging (DOSI)
against magnetic resonance imaging (MRI) for this purpose. In previous pilot
studies by the research team, DOSI has proven potential to be a more accessible
and informative method for research into breast tissue composition compared to
other imaging modalities, but it*s performance still needs to be assessed on a
large scale.
• evaluate the relation between (changes in) breast tissue composition and milk
production.
• define the duration of human post-lactational involution, which is currently
unknown.
• compare breast tissue composition before pregnancy to after post-lactational
involution.

A longitudinal observational study

The subject does not undergo any invasive, painful or harmful actions. No MRI
scans will be performed during pregnancy. Participants decide themselves
whether they breastfeed and for how long. That decision will not influence
their participation.
The non-invasive DOSI measurements in this study are based on the use of
low-power light. These DOSI measurements are painless, safe and do not affect
the physiology of the breast. The DOSI probe is similar in size and design to
an ultrasound probe. During the measurements, the DOSI probe is gently moved
over the breast and scans a small surface with a laser beam. The following
measurements will be performed:
• DOSI. A DOSI scan will be performed every six weeks from the end of the first
trimester until 12 months after the stop of breastfeeding (or delivery, for
non-breastfeeding participants). The measurement will take approximately 10
minutes, depending on the breast size. During the measurement, the subject lays
still in a relaxed, supine position. Each measurement session takes
approximately 30 minutes in total and is performed at a time and location of
the subject's choice - for example, at their home.
• MRI. The subject will only be asked to come to the University of Twente for
an additional MRI examination next to the DOSI scan on six occasions
post-partum. This will be within 6 weeks post-partum and within 1, 3, 6, 9 and
12 months post-breastfeeding. The MRI scan takes approximately 45 minutes in
addition to the DOSI scan time, so in total the measurement session will take a
maximum of one hour and 15 minutes.
No contrast agent is used for the MRI measurement, which makes the measurement
non-invasive. All scans are made under the supervision of an experienced
technician. During the measurement, the subject will lie in the MRI scanner for
a maximum of 30 minutes. All surfaces that are in contact with the subject
during the DOSI and MRI measurement are sterilized before and after each
measurement.
• Before pregnancy. Only if participants are included before pregnancy, one
additional DOSI and MRI measurement are made before pregnancy.
• Milk production. For breastfeeding participants, milk production will be
assessed at one time point, 4 to 6 weeks postpartum, with a 24h breastmilk
production test weight method. The mother will weigh the infant before, and
after feeding over a period of 24 hours and share these results with the
research team. As an additional (indirect) indicator of milk production, we
will ask the participants to share the growth curve of the infant as measured
at the *consultatiebureau* by the *Gemeentelijke Gezondheidsdiensten* (GGD).

This research design minimizes the time burden for the subject. Depending on
the duration of the breastfeeding period the time of the study is 2 to 3 years.
Regardless of whether the participants still breastfeed their child, the study
will come to an end in February 2027.
Participation in this study does not provide any direct benefit to the
subjects, but it will aid in a more fundamental understanding of breast
development during pregnancy, lactation and post-lactational involution. In the
future, these insights can potentially contribute to a better understanding of
the prevention and treatment of breastfeeding problems and breast cancer.