Milk Biomarkers of Secretory Activation in Mothers of Premature Infants
by Anne Eglash MD, IBCLC, FABM
What are ways that we can detect the onset of secretory activation (aka when the milk comes in)?
There are many reasons why lactating individuals may have a delay in secretory activation (SA), including high BMI, premature delivery, cesarean birth, stress, breast pump dependency, gestation diabetes, pre-eclampsia, among others. The most common way that researchers have measured the onset of SA is by parental perception, such as breast fullness, change in color of milk, or milk volume.
Why do we need to know about the timing of SA? Knowing whether SA has occurred helps us to understand the possible cause(s) for an individual’s low milk production. For example, when an individual has low production in the second week, it is often unclear if this is due to low glandular tissue or a delay in SA due to medical conditions such as insulin resistance or early postpartum birth control.
Research can help us understand how birth practices and health conditions impact SA, but we need to understand the best way to measure SA.
The study for this week is a review of the different milk biomarkers used to measure SA. The researchers reviewed 40 studies that compared milk biomarkers of SA in pump dependent mothers of preterm infants with healthy term mothers and identified 6 articles that met their criteria for inclusion.
The 4 primary milk biomarkers indicating SA include sodium (Na), lactose, citrate, and total protein. Most studies were small, and the studies collected milk at different time periods and at different frequencies. Some of the studies used 1-2 biomarkers, while others used all 4. Despite the different methodologies, there were some consistent findings. See the question for details!
- Maternal report of ‘milk coming in’ strongly correlates with biomarker measurements of SA.
- Mothers of premature infants who ‘come to volume’, meaning express ≥500ml/day by day 14, are more likely to have normal biomarkers of SA much earlier postpartum as compared to those who express <500ml/day by day 14.
- Biomarkers of SA are not associated with milk volume.
- Increased pump frequency among pump-dependent mothers of premies is strongly associated with earlier SA and coming to volume at 2 weeks postpartum.
- A BMI ≥ 27 among pump-dependent mothers of premies has been found to be associated with a slower rate of rise of milk volume in the first few weeks compared to those with a BMI < 27.
- Pump-dependent mothers of premies have a higher risk of a delay or impairment of SA.
See the Answer
Abstract
Background
Lack of mother’s own milk (MOM) at discharge from the neonatal intensive care unit (NICU) is a global problem and is often attributable to inadequate MOM volume. Evidence suggests that the origins of this problem are during the first 14 days postpartum, a time period that includes secretory activation (SA; lacto-genesis II, milk coming in).
Objectives
To describe and summarize evidence regarding use of MOM biomarkers (MBMs) as a measure of SA in pump-dependent mothers of preterm infants in the NICU and to identify knowledge gaps requiring further investigation.
Methods
An integrative review was conducted using Whittemore and Knafl methodology incorporating the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. A search using electronic databases MEDLINE (through PubMed) and CINAHL (Cumulative Index to Nursing and Allied Health Literature) and reference lists of included articles was conducted.
Results
Of the 40 articles retrieved, 6 met the criteria for inclusion. Results revealed the following five findings: (1) Achievement of SA defined by MBMs is delayed and/or impaired in mothers of preterm infants. (2) MBMs are associated with pumped MOM volume. (3) Achievement of SA defined by MBMs is associated with pumping frequency. (4) Delayed and/or impaired achievement of SA defined by MBMs may be exacerbated by maternal comorbidities. (5) There is a lack of consensus as to which MBM(s) and analysis techniques should be used in research and practice.
Conclusions
MBMs hold tremendous potential to document and monitor achievement of SA in mothers of preterm infants, with multiple implications for research and clinical practice.
It seems clear from this review that maternal report of ‘milk coming in’ is not an accurate measure of onset of secretory activation. The research studies found that milk volume was associated with biomarker results of secretory activation. Mothers who ≥500ml/day by day 14 had normal biomarkers of SA by day 4 postpartum on average. Mothers who expressed less than 500ml/day by day 14 had normal biomarkers of SA by day 9 on average.
The frequency of pump sessions each day are strongly correlated with earlier SA and coming to volume by day 14 postpartum. Pumping, however, needs to be defined, as optimizing pump use with appropriate vacuum and shield size is important to prevent nipple pain, trauma, recurrent compressed ducts, and to maximize milk removal. Most studies do not describe pump dynamics.
The authors discussed the clinical usefulness of milk biomarkers in practice. Milk citrate and lactose levels are cumbersome to measure, whereas a spot milk Na is easy to measure with a simple office tool.
Madison Hendry
Expressing milk within the first hour makes a difference vs expressing after the first hour birth or 6 hrs after birth
IABLE
The Parker studies from 2012 and 2015 indicated that expressing milk in the first hour made a difference in milk volume later. However, those were not large enough studies, nor were they randomized controlled trials. They repeated their work in a randomized controlled trial in 2020 and demonstrated that pumping in the first hour is NOT what makes the difference in producing sufficient breast milk. They found that pumping within the first 6 hours was important AND pumping frequently was the key to success. We need to be stressing frequency, and not stressing the importance of pumping in the first hour.
I have found that people stress that they ‘ruined’ their chances of making enough milk if they don’t pump in the first hour, so it is important to not perpetuate this disproven theory.
However, I would add that expressing milk in the first few hours for premature infants is important to provide colostrum for oral immune therapy.
Dorothy Macias
Thank you for this information. I have seen the challenges that the nurses have when recovering a mom, let’s say with severe PIH,and then needing to start a pump baby going to NICU. I see that it’s a struggle and challenge even after 6 hours have passed to get a pump started. I really have encouraged the nurses to try to teach hand expression prior to delivery so that can be done immediately after delivery. It works for a little while then goes off by the way side. Lactation consultants are way under staffed and at times we don’t get to them until the next day. I do stress the frequency, day and night, and not to skip night time feedings. There has to be a different approach.