Lactation is a remarkably dynamic process. Interwoven genetic and environmental factors activate different biological signals over time so that mothers produce breast milk perfectly suited to meet their growing babies’ changing dietary needs. Yet, most women stop breastfeeding well before the guidelines recommend (1–3). Now, results from a new study unaffiliated with BIOMILQ say that it’s not only psychological or circumstantial factors that drive breastfeeding behaviors, but also maternal genetics.
Stress and the return to work (4) have been implicated in mothers discontinuing breastfeeding too soon. Additionally, in a phenomenon called PIMS (5), or perceived inadequate milk supply, mothers wean their babies off breast milk based on the belief that their babies aren’t getting enough. This may be based on cues such as an infant crying after a feed, for example (6).
Reports from around the world suggest that over half of all mothers discontinue breastfeeding early due to PIMS (7–11) Meanwhile, research using sensitive analytical techniques to measure lactation yields (such as tracking infant weight gain or weighing babies before and after a feed) show that the proportion of women whose milk supply is truly unable to sustain growth may be closer to 10 to 15 percent (12,13). In the absence of defined reference ranges to describe the normal physiology of human lactation, distinguishing PIMS from a physiological inability to produce enough milk is difficult. Crucially, managing physiologically insufficient milk supply as if it were a matter of the mother’s inaccurate perception can have substantial consequences for both mother and baby. As these two scenarios warrant different types of support, there is a need to identify markers that can distinguish between perceived and objective low milk supply.
In a recent study, Penn State College of Medicine researchers put forward an interesting hypothesis: PIMS could also be influenced by maternal genes (14). Indeed, many genetic correlates of milk production have been identified in dairy species (15), but this hypothesis has rarely been explored in humans. Chandran and colleagues followed a cohort of around 200 breastfeeding mothers, collecting medical, demographic, and breastfeeding data for over a year. They also genetically screened a subset of 88 of the mothers, roughly half of whom had PIMS.
As part of their analysis, the team honed in on a panel of 18 lactation genes, such as prolactin (a lactation hormone). They were on the lookout for single nucleotide polymorphisms, or SNPs, in these genes—naturally occurring gene variations that control many aspects of human health. Some SNPs point to an individual’s risk of developing a chronic disease (16), or their susceptibility to drug side effects (17), for instance.
In a breakthrough finding, the researchers found that mothers with PIMS had a particular SNP in the MFGE8 gene. Women with this gene variant, called rs2271714, breastfed exclusively for an average of 4.7 weeks. Meanwhile, those without the variant breastfed almost three times longer. Mothers with or without the variant produced about the same amount of breast milk daily.
Graphic courtesy of Tara Fernandez
There are about 500 different proteins in breast milk, and MFGE8 (or milk fat globule EGF and factor V/VIII domain-containing gene) holds the genetic code for lactadherin, one of the main proteins in the milk fat globule (MFG). Complex and nutritionally dense, the MFG’s composition is fluid, subtly shifting throughout lactation (18). Lactadherin plays a diverse role within the MFG: it controls milk secretion, defends against bacteria and viruses, and establishes the baby’s immune defenses (19) Beyond lactation, lactadherin also regulates other biological processes such as forming blood vessels and wound healing (20).
How is the MFGE8 gene variant linked to lactation, and why are women with rs2271714 more likely to have PIMS? Unfortunately, we don’t know yet. This avenue of research has yet to be explored in human studies, but research on goats and mice may offer some clues.
One study found four MFGE8 gene variants among goats, three of which were linked to diminished milk yields (21). In mouse models of lactation, mutations in the MFGE8 gene triggered disruptions in mammary gland remodeling, a physiological process that occurs towards the tail end of the lactation period (22). In addition, variants of MFGE8 may impact the functionality of lactadherin, ultimately altering the MFG (23).
Chandran’s study sets the stage for follow-up investigations on how the maternal genetic landscape steers breastfeeding behavior. Still, limitations in the study design leave unanswered questions. For instance, to quantify the amount of breast milk produced daily, the researchers relied on estimated feeding volumes provided by the participants rather than using more objective measurement methods. Consequently, we cannot conclusively determine whether the rs2271714 variant altered breast milk yields. This is a common issue in lactation research. Techniques such as measuring the babies’ weights down to the gram before and after a feed (24) or labeling breastmilk with radioactive tracers (25), while more accurate, aren’t always practical or accessible in the field.
The interplay between genes, lactation, and breastfeeding practices is an exciting new frontier in lactation science that, in the future, could shape better, data-driven frameworks to support nursing mothers. For example, the authors propose that performing routine genetic tests could identify mothers with the rs2271714 variant who have an elevated risk of PIMS. Offering these women targeted lactation advice, nutritional supplementation, and other early interventions to prevent PIMS may help extend their breastfeeding windows.
In addition, the field would benefit greatly from simple and standardized approaches to measuring lactation yields. According to experts, well-defined clinical reference ranges are available for every organ system except lactation (26).
This piece was primarily written by Tara Fernandez, Ph.D., with input from the BIOMILQ team. Tara is a Science Communicator sharing stories on the latest discoveries, innovation, and technologies that are set to transform how we protect human health and wellbeing. You can read more of her work here.
References:
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