What the research tells us about the larger bodied woman and breastfeeding + supportive clinical skills. Dr Kate Rassie video 11 March 2025
Weight-inclusive, destigmatising care of breastfeeding and lactating women
Neuroprotective Developmental Care (or the Possums programs) supports the use of respectful language which is woman-centred and avoids the stigmatising of larger bodied women.
This presentation on larger bodied women and breastfeeding, below, is by endocrinologist Dr Kate Rassie MBChB FRACP Dr Rassie works at Monash Health and Jean Hailes for Women's Health, Melbourne, Australia, and is finalising a PhD at the Monash Centre for Health Research and Implementation, Monash University).
Time stamps
| Topic | Pdf slide number | Time stamp |
|---|---|---|
| Obesity pathophysiology | 5-14 | 02:58mins |
| Obesity stigma | 15-17 | 16:19mins |
| Impacts of obesity on breastfeeding | 18-35 | 18:53mins |
| Optimising breastfeeding for women with obesity | 36-42 | 36:01mins |
| Weight (and weight loss) during breastfeeding | 43-50 | 45:39mins |
Recommended resources
Woman-centred language and weight-inclusive care of breastfeeding and lactating women
'Intuitive eating' in the perinatal period
What works best for you and your baby when you have a generous breast?
A woman-centred approach to weight stigma (downloadable pdf)
The body positive birth alliance
Transcription
Pam: I will welcome you all and start by acknowledging the traditional custodians of the lands upon which I live and work, the Yuggera and Turrbal peoples, and pay my respect to elders past, present, and emerging. And I am absolutely delighted to welcome back Dr. Kate Rassi, an endocrinologist at Monash Health and Jean Hales for Women's Health in Melbourne, and also right at the end, as I understand it, nearly there with the PhD, which is with the Monash Centre for Health Research and Implementation. All of us, I think, absolutely loved Kate's last presentation on diabetes, PCOS, and lactation, and just absolutely delighted, Kate, that you've made the time to come back tonight to talk to us about obesity and breastfeeding. So I think without further ado, I'll hand over to you.
Kate: So I, as Pam said, I'm Kate Rassi. I'm an endocrinologist at Monash Health, and I also work at Jean Hales. And as Pam has also said, I'm coming to the very pointy end of my PhD candidature, and I've been looking at the links between metabolic health in women and lactation outcomes. So no conflicts of interest in relation to tonight's material.
And this first slide really is just to point out that what we're talking about tonight is increasingly becoming our norm. So it's now the case that the majority of Australian mothers entering pregnancy are affected by either overweight or obesity. And if you restrict that down to just obesity, it's around about a third. So tonight I'm going to talk, I'm going to start off by just talking about obesity in a general sense before we proceed to its impacts on lactation. I'm going to talk a bit about obesity stigma, which is really important within the health system. And then I'm going to move to talk about the impacts of obesity on breastfeeding. I'm then going to propose some practical strategies and ways that we might look to optimise breastfeeding for women living with obesity. And then we're going to talk about weight and intentional weight loss whilst women are lactating, because I think that's something that regularly comes up in clinical practice. So this is maybe the most important slide of the lecture, and I'm going to bring it up a few times as I talk to some of the points here.
Obesity Stigma [00:02:46.23]
Kate: But I think there really has been a paradigm shift in the way that medicine thinks and talks about obesity, even over the last sort of 10 to 15 years. So the statements on this column on the left represent the way that I recall being taught to think about obesity when I was at medical school around 10 to 15 years ago. And on the right, these statements summarise my current understanding. And I vividly remember, as many of you will too, these obesity lectures and the way that they were littered with these sort of stock images of burgers and people sitting on sofas and that sort of thing. And there was this real implication, even in what was a very respectable academic curriculum, that obesity was an individual lifestyle choice. We now know that obesity has a really significant genetic component, and also that it has environmental influences which are systemic and universal. So if we think a little bit about the genetics of BMI, this is really interesting. And our understanding of this dates back to the late 20th century at a time when these twin studies were in vogue. You had these whole series of these quite elegant studies, and these really informed our understanding of how genes predict BMI. So this graphic you can see here is taken from a 1970s study, and they looked at 101 twin pairs. They've just shown a few in the photos. You can see that these top pairs here are monozygotic or identical twins. So they're genotypically identical individuals, and these are dizygotic twins or non-identical twins who are like siblings. And you can see that the monozygotic twins have a really tight correlation in their BMI, which is much less the case for the dizygotic twins. Even more compellingly, there are lots of other studies that take monozygotic twin pairs like these ones, and they look at twin pairs raised together and twin pairs raised apart. And interestingly, this really tight correlation in BMI that you see for identical twins seems to persist even when those twins are raised in different family and therefore very different food environments. So that's informed a lot of our understanding about heritability of BMI. Our current understanding is that the genetic contribution to an adult's BMI is around about 40 to 70 percent. And if you've got one biological parent with obesity, you're at three to four times the risk of obesity compared to those who don't. If that's both parents with obesity, your risk of obesity is elevated tenfold. In most cases, that inheritance is polygenic, so there are hundreds of different associated genetic loci. There are a few conditions, Prada-Willi springs to mind, where you have monogenic obesity, but those really are the exception rather than the rule. And this is probably further modified by epigenetics. So whilst there's a big genetic component at any given point in history, we also know that over generations, our environment has become more and more obesogenic.
And obesity is an environmental disease just as much as lead poisoning or asbestosis. That would be the argument of many epidemiologists. So this is an interesting graph showing its NHANES data, and it's showing obesity trends in US adults aged over 20, and it's just over the last 20 years. And I think the graph is an alarming one in and of itself, but actually it's the projections off this side of the graph that are even more concerning. So over this 20 years that the graph captures, the obesity rates went from 30 to 42 percent. In actual fact, if you extrapolate out to 2030, that's projected to be up at 50 percent. And severely obese, this is 40 plus, a BMI of 40 plus, doubled over this time period from 4.7 to 9.2, but that's actually projected to be out to 25 percent by 2030. And that's just five years away. So really alarming projections in terms of future trends in obesity. Why does that happen? Look, I think we're eating more. There's been massive shifts in our food environment. And this graph shows the changes in estimated food intake in children and then in adults in the US from the 1970s to the early 2000s. And this is data taken from the US food supply. And you can see that there's been a really significant increase in the mean caloric intake per day over this time. So in the order of about 350 calories a day for kids and about 500 calories a day for adults. There's also increasing evidence to support the role of ultra processed foods. And this is a term that you're likely to see a lot more in coming years. So ultra processed foods are foods that have undergone chemical processing associated with industrialized food production. And they've typically also got additives in them that are associated with the development of obesity. So this here is a graphical abstract. It's taken from the journal Cell. And it's 2019 randomized controlled trial. And in this trial, they had 20 adult inpatients who were randomized to either ultra processed or unprocessed food for 14 days. And this trial was a crossover design. So each group completed both arms of the study. They were in a highly controlled inpatient environment and they were given three meals a day plus snacks on hand and they were just asked to eat ad libitum. And they matched the meals and snacks for the total calories and macronutrients. But one diet was comprised of unprocessed food and the other diet of ultra processed food. And you can see there was a really clear trend that over the two weeks of eating the ultra processed diet, participants were consuming about 500 extra calories a day, which is quite a lot. And that was mainly carbohydrate and fat in terms of its macronutrient composition. And over that time, they experienced a statistically significant weight gain of around about a kilo over the two weeks on the ultra processed diet, whereas with the unprocessed diet, there was a similar magnitude of weight loss. So overall, we can see that there have been these really significant social changes, these changes to our food environment that have driven this longitudinal slow creep in our population BMI over the last 50 or so years. And I think when you look at that, and then you combine that with the genetic data that I've also told you about, there's really little excuse remaining to view obesity as being a result of poor individual lifestyle choices.
So here's another area where our understandings really changed over the last 10 to 15 years. There used to be this really widely held belief that weight loss was a mind over matter situation and that any individual, if you are sufficiently motivated and disciplined, you should be able to lose weight through modification of diet and physical activity. And we now know that this is fundamentally untrue. And that in fact, body weight is vigorously defended at the level of the central nervous system, and that it's not just a matter of nervous system, and also via endocrine mechanisms. So appetite and body weight are really tightly regulated at the level of the hypothalamus. So particularly this area of the hypothalamus called the hypothalamic arcuate nucleus. And this is an area of the brain that operates below the level of an individual's conscious awareness. It's always receiving and integrating lots of hormonal inputs from the GI tract, from the pancreas and from adipose tissue. And in really simplistic terms, signalling up this POMC pathway shown here in the green, drives an eat less and store less response. Whereas signalling up this purple pathway, the AGRP pathway, sends eat more and store more messages. And you might have heard of set point theory. And that posits that for many adults, it's the counterbalance of those two opposing systems that allows regulation of body weight within a range of a few kilograms upward or downward. In actual fact, we're probably better to refer to it as a set range rather than a set point. I think that there's increasing recognition that this brain circuitry may actually be fundamentally different in some individuals. And some individuals probably do trend towards an AGRP dominant picture with a really strong appetite drive. And that in particular, their pathways may be more susceptible to environmental influences. And that becomes particularly important when as individuals, we're placed in this era of really freely available, highly processed food choices, the result being obesity. I just included this little picture here of this woman. So her name's Fatima Cody Stanford, and she's an obesity medicine specialist out of Harvard. She's an international expert in this field, and she's a really good science communicator.
So if you ever feel like doing a deep dive into obesity, I would hunt out her podcasts and her YouTube videos because she's really captivating and she's excellent at expressing these concepts. So can you lose weight with lifestyle interventions given all of that? Well, you can. We do have a large number of trials which repeatedly demonstrate the short term efficacy of diet and lifestyle interventions, particularly very low carb and very low energy diets. And particularly again, if they're structured and supervised. The emphasis here is on the short term. And there are a number of graphs I could have shown you here, but this is one, it's just a very representative trial of this sort. It's taken from the BMJ. It was done in 2018. You have about 300 adults who are living with obesity, and you randomize half of them to usual care shown here in the blue. They're given some behavioral support from a practice nurse. They're given a diet program with a modest energy restriction. And then you randomize the other half to a very low energy diet meal replacement, something like Optifast. They take in 800 calories for the first eight weeks, and then that slowly increased. They get weekly support from an experienced dietitian. And you can see that by the end of 12 months, the participants in the intervention group have lost 12, have lost 10.7 kilograms, whereas those with usual care are down only three kilograms. And the authors of the study talk about how all of their cardiovascular and metabolic parameters improve and say, look, this seems to be a tolerable diet. It leads to substantially greater weight loss and significant improvements in cardiometabolic disease risk. But the really key thing here to note is this trial duration of one year, which is really typical for studies of this ilk, because almost inevitably, over time, that weight is regained. So this is a graph taken from a meta-analysis of 29 long-term weight loss studies in the US. In order to get into this meta-analysis, the trial duration had to be more than two years. And these authors added up all the weight that was lost in the individual studies, and then they tracked the way it was regained after the intervention was terminated. And you can see that by two years out from the intervention, more than half of that lost weight will be regained. And by five years, almost 80% of it is regained.
So why does that happen? Well, when a patient with obesity loses 15 to 20 kilograms via intensive diet and lifestyle interventions, there's this series of really powerful physiological changes that kick in, in order to bring them back to their previous set point. So you get a sustained reduction in circulating levels of the satiety hormones, the fullness hormones, things like amylin, insulin, leptin, and cholecystokinin. And you get persistent increases in orexigenic or hunger hormone, the main one of which is ghrelin. You also get reductions in your basal metabolic rate. And all of those physiological adaptations to weight loss explain this really near universal phenomenon, whereby if you lose weight on a diet initially, even if you maintain the dietary strategies, your weight loss will slow and plateau, and eventually weight is regained. And I actually explicitly discuss this concept with my patients. I may show them a diagram a little bit like this. And I'll talk about the fact that their bodies are designed to fight back against weight loss. So any weight loss that they do achieve has required them to swim against the current of their inbuilt physiology. Once that weight's lost, they're going to have to keep on swimming against the tide to maintain their lower weight. And I think that sounds depressing, but in my experience, many patients will welcome that explanation because they are used to repeated implications from health professionals that their weight regain represents a personal failing. And this brings me to talk about weight stigma, which is really important. It's a pervasive stereotypical discriminatory perception that being larger bodied is inherently pathological. And also that individuals are solely responsible and therefore subject to judgment and blame for their own weight. And it's associated with this view that a particular body size is more morally valuable or worthy than another. It's now increasingly acknowledged as a chronic social stress that actually may be independently a key contributor to the adverse health outcomes of obesity, aside from the cardiometabolic impacts of their weight. So it's associated independently with increased blood pressure and oxidative stress and higher cortisol levels and poorer glycemia. It's associated independently with increased mortality, even after you account for the added BMI, and it increases risk for further weight gain and obesity over a life trajectory. Unfortunately, pertinent to what we're talking about today, it is gendered. It's more than twice as frequently experienced by women than men, and it's experienced by women at lower BMIs than men. It's particularly common in the healthcare setting and it's rife in the preconception, pregnancy and postpartum space, which is a big issue now that we know that around about a third of women with reproductive age are living with obesity. So I think the onus is on us as clinicians not just to know about the complex pathophysiology of obesity, but also to have a compassionate and a person-first approach to those who are living with it.
Just a word now about language, because I think this really matters, and one really simple way of working this approach that I'm describing into our practice is to consider person-first language. I'm sure I'm preaching to the choir here, but you think about the term an obese woman that uses a woman's body weight as her defining identity. So we wouldn't call a patient with cancer a cancerous patient, but if we turn that around and we say a woman with obesity, we are placing her personhood first, both in the sentence and also in a broader sense, and her obesity in that context becomes a disease just as neutral as any other. A woman with obesity, a woman with rheumatoid arthritis. So I actually don't use the term obese at all with my patients directly, but we certainly do use it in the medical fraternity and discussions with our colleagues in the literature, and I think we've just got to be really careful about consistent and respectful practice. So I'm now going to move on to talk about obesity in the context of breastfeeding, which is of course why we've all logged in tonight, and I think it's important before I move to focus in the main on the mother for the rest of the talk, just to acknowledge the potential metabolic benefits of breastfeeding for offspring in terms of obesity and therefore for society at large. So I've been talking a lot about the heritable nature of BMI and also about the social trajectory towards increasing obesity rates. If there was a protective effect of breastfeeding in an intergenerational capacity, that would have marked public health benefits, and indeed that actually does appear to be the case. So again, there's a big caveat here. We're looking at observational research. We always have to think about confounding. We always have to think about reverse causality. But this is probably the biggest and most comprehensive systematic review to date, 2023, commissioned by the WHO, almost 170 studies included in it, and they found that overall breastfeeding appeared to be protective for the offspring against overweight and obesity with an odds ratio of 0.73, which was significant. And then when they restricted that to a subgroup analysis where they only looked at the very high quality studies, the largest ones, those that were considered to have the most robust control for confounding, that remains statistically significant. Unfortunately, though, we do have pretty solid evidence that women with obesity across the world, across the developed world, have suboptimal breastfeeding outcomes. In particular, maternal obesity is associated with earlier weaning. There's some evidence to support this. Initiation rates generally are only slightly lower among women with obesity, but a BMI of greater than 30 is associated with significantly higher odds of stopping exclusive or any breastfeeding in the early postpartum. And this is an illustrative table. It's taken from a big Norwegian cohort study, 50,000 mother-baby dyads. And you can see that when you compare women in a normal BMI range, those with class 2 plus obesity, which would be a BMI 35 plus, the rates of breastfeeding initiation don't look too different, 99.6 versus 97.4%. But when you look at extended or exclusive breastfeeding, extended exclusive breastfeeding out to four months postpartum, there's a huge difference. So you're looking at 62.9% versus 37.8%. This table is just the unadjusted numbers. But later in the same paper, they did a really elegant logistic regression where they adjusted for key factors like age, like socioeconomic status, like education. And again, they found that women with obesity were twice as likely to not be breastfeeding at all at four months postpartum than their counterparts of normal weight.
Impacts of obesity on breastfeeding [00:21:21.08]
Kate: The other thing to note is that breastfeeding difficulties in our lactating mothers with obesity do tend to manifest early. So infants born to mums with obesity have higher odds of requiring medically indicated supplementation during their hospital stay. And that's even after you correct for conditions like diabetes, like cesarean delivery, inductions, preeclampsia. And also, we know that the odds of maternally requested formula use are higher in mums with obesity. Delayed onset of lactogenesis is really common in this cohort that's defined as a lactogenesis onset beyond 72 hours after birth. And some large US cohorts have that at over 50% of women with obesity. So what are the mechanisms there? What links obesity to suboptimal lactation outcomes in our women? I think we've got to think about this in three broad buckets, three broad categories of explanation. The first of those is physiological reasons. The second is the clinical reasons. And the third is the broader psychosocial context. I'm going to talk about each of these in turn. So let's start with the physiology. So abnormal prolactin dynamics is a really interesting one. A lot of this is extrapolated from rodent models. If you take rodents that are obese, or alternatively, rodents that are fed a really obesogenic diet during their lactation, they have reduced milk yields. And that's at least in part due to something going wrong with prolactin signaling. And it's probably rather than absolute differences in prolactin levels in rodents, it's probably about prolactin resistance. So lower levels of prolactin receptor expression and reduced downstream prolactin signaling. So prolactin doesn't seem to work as well. This is a really lovely diagram based on what might be happening. And it's based on rodent models, but it's a proposition for what might be going on in humans. And it's a bit busy, but I'll step you through it. So this is on the left, on the left hand side in the healthy, non-obese state. You've got plenty of these. You can see plenty of these healthy blue prolactin receptors sitting here in the membrane of this mammary epithelial cell. And also in the membrane of this mammary adipocyte. And when the prolactin molecules bind, they trigger this really nice orderly intracellular signaling cascade via JAK and STAT, which results in the translation of these milk protein genes. They've shown here WAP and CSN2. On the right hand side, there's the obese state. And you can see here that it's characterized by a reduced number of these prolactin receptors in the membrane and a loss of this nice orderly subsequent intracellular signaling. And that's essential to milk production. You'll also see here that there's a surfeit, an excess of mammary adipocytes in the breast tissue in the obese state, and that prolactin signaling is also impaired there. So what about in humans? Well, we don't have that kind of elegant mechanistic research, but we can certainly extrapolate that similar things might be happening in terms of prolactin receptor expression not working as well and prolactin signaling downstream of the receptor not being as effective.
We've also interestingly got some evidence pointing towards lower absolute prolactin levels in women with obesity. So this is a 2004 study, widely quoted in the literature, conducted in New York in the early 2000s. So 23 women with normal weight and 17 living with overweight and obesity. They measured prolactin at baseline and then at 30 minutes into a suckling episode at 48 hours postpartum. And they found that the women with obesity had a significantly lower prolactin response to suckling when compared with normal weight women. I think the caveat here, the physiology of this is really interesting. They didn't in the paper link it to actual breastfeeding outcomes. And also I haven't seen that replicated, but I think it theoretically makes sense, but needs obviously to be substantiated. So the second arm of the potential mechanisms linking obesity to poor lactation outcomes corresponds to insulin resistance. So we know that secretory activation is a time of really upregulated genetic expression in the mammary epithelium. The breast is having to become a milk protein factory. And we're increasingly realizing that many of the key pathways here are insulin sensitive and require insulin signaling, the interaction between insulin and its membrane bound receptor in order to be effectively activated. So insulin's probably really important to breast development and milk synthesis. It turns on a whole lot of the genes associated with those processes. So if you have low absolute levels of insulin, or if you have insulin resistance, which we know is really common in obesity, that may impair milk production at the level of the lacticide. So you might recall me showing this slide in a previous presentation. It comes from the group of Laurie Nomsen Rivers, who's an excellent lactation researcher out of Cincinnati. And she's the person to look up if you're ever looking at literature linking maternal metabolism to suboptimal lactation outcomes. So this was a case control study. These women were recruited into the study at two to 10 weeks postpartum on the basis of really low milk supply. They were coming to a clinic where that was the presenting complaint. And they defined low milk output as less than 300 mils per 24 hours. And they compared these women to some nested and external controls with more physiological milk output or more normal milk output. So these women with the severely low output had been thoroughly evaluated for correctable issues, such as infrequent or ineffective breast emptying. And they were emptying their breasts throughout the study as frequently, if not more frequently, than the women with the normal output.
And they were metabolically profiled. So the group looked at a number of metabolic parameters in this low supply group, their BMI, their waist circumference, their glucose, their insulin, their lipids, their blood pressure. And they came up with this composite metabolic severity score. And here are all those scores plotted on a graph with their 24- hour milk output on the y-axis. You can see here they're all less than 300. And then their metabolic health z-score on the x-axis. And what you can see here is that the woman with the very low supply, the woman less than 300, the gray circles, are massively overrepresented in this zone of worse than average metabolic health. You'll also see these circles, these ones here where there's a faint circle around the outside. Those are the GDM cases, the gestational diabetes cases. And you can see that they're numerically significantly overrepresented compared with these ones. As was class 2 plus obesity. So that was massively overrepresented in the low supply group too. And these authors suggested that metabolic dysfunction may be one of the key risk factors for severely low milk supply. So this is becoming a real interest area within the lactation literature. This slide summarizes really what I've just shown you graphically about the results of that study. Almost every measure of metabolic health was worse in that group with the really low supply. What I find really interesting is after this little and here was the second linked paper from this group. In this paper, they went a little bit further. And what they did was they took a subset, five of those women with the really, really low supply. And they looked at the RNA transcripts that were actually floating around in the lactocytes of those women. So they're getting an idea of how gene transcription is happening.
And what they found was that in the woman with the really low supply, those who tended to have inferior metabolic health, they had far fewer RNA copies of those important insulin sensitive genes in their lactocytes. And so this is a really lovely, elegant, mechanistic demonstration of the fact that it may well be defective insulin signaling that's interfering with milk production in these women with obesity and insulin resistance. The third arm of the physiological explanations for obesity impairing breastfeeding is this idea I think we're all aware of now is that obesity is a state of low grade chronic inflammation, that there are lots of these inflammatory cytokines that are elevated in the state of obesity and inflammation has repeatedly been shown to impair lactation and rodent models. Probably a state of chronic inflammation in particular targets this important enzyme called lipoprotein lipase. So in mammals, lipoprotein lipase is important at moving long chain fatty acids from the blood into the milk and reduced lipoprotein lipase activity may impair substrate delivery and therefore milk supply. And interestingly, in that study that I just talked about, where they looked at the RNA copies and the lactocytes of those women with the really low milk supply, they also found 1.8 fold down regulation of lipoprotein lipase activity, in addition to the less copies of the insulin sensitive genes. So in addition to defective insulin signaling disrupting insulin sensitive gene expression, we've also got impaired lipoprotein lipase activity and reduced substrate delivery at the level of the lactocyte. So moving on now from the complex pathophysiology to the more pragmatic clinical considerations. So we know that from a clinical point of view, I think it's really important we acknowledge that obesity is a major obstetric risk factor. So women with obesity have an increased risk of adverse pregnancy outcomes, almost everything really, preeclampsia, preterm birth, delivery, cesarean sections, NICU admissions, birth defects, hypoglycemia, jaundice. And we all acknowledge that those events have potential themselves to derail an early breastfeeding relationship. They can delay skin to skin, they may mandate supplemental feeding, they may separate the mother-baby dyad. But whilst those are really important factors, they're definitely not the whole story because we've got really good evidence suggesting that the relationship between obesity and suboptimal breastfeeding outcomes will persist even after you correct for those factors. So it's not that alone, although that's certainly a contributor
So this is a lovely quote, it's taken from a systematic review by our colleague Lisa Amir and it dates to the late 20th century in the wet nurse era. And we now know that there's no relationship between breast size and milk supply, as this commentator said. They said overly large breasts usually portrayed a true poverty of milk for the heavy fat parts of the breast impeded the separation of the milk and its free passage through the narrow conduits to the nipples. I think whilst we may have debunked that line of reasoning, there certainly are practical challenges that face larger breasted and larger bodied women in establishing comfortable, effective breastfeeding. So we know that fit and hold can be more challenging. Women may have difficulty visualising the areola. The areola themselves can be broader based and the weight of the breast on the infant chest can present challenges. There's some evidence too for higher rates of nipple shield use in mothers with obesity. Psychosocial factors are a final important thing to consider and the first of these is negative self-perceived body image, which we know from literature is more common when women with obesity when compared to their lean counterparts. Body dissatisfaction itself has been shown to influence breastfeeding duration and there's one French study where women with obesity most commonly cite indecency as a reason not to initiate breastfeeding in one study. They were more likely to feel uncomfortable breastfeeding in public at three months when compared to their reference weight peers.
There's also this issue of implicit and also explicit weight bias in the healthcare setting and that leads to inequitable access to support for breastfeeding mothers. So in one oft-quoted US study, about 20,000 women, 20% of the mothers had obesity. Those with obesity were less likely to get good information about breastfeeding, to get breastfeeding assistance, to get a telephone number for help. They were less likely to breastfeed in the first hour after delivery or to be encouraged to breastfeed on demand and those factors all remain significant. All those findings all remain significant once you adjusted for the mode of delivery and for the key socio-demographic factors there. So it wasn't just that they had more complex deliveries. And then finally we've talked about this fact that weight bias itself, that the chronic allostatic load of living in a larger body with all of that entails, may lead to inflammation and that itself may further physiologically impact on and impair milk production. So I think this all sounds really depressing and we've got to think about how we can intervene and I'll preface this by saying I'm an endocrinologist, I'm not a lactation consultant and there may be some audience members here who can expound on some of these practical points much more eloquently than I. But I think we should think first of all about what the literature is saying about practical suggestions for optimising breastfeeding success in our patients who are living with obesity.
Practical strategies [00:35:40.10]
Kate: Well what does the literature say first of all about structured clinical interventions? What trials have tried to improve breastfeeding rates for women living with obesity and what's been the outcome? There are a number of trials, there's probably 15 or so across really different countries, across really different social contexts. One trial looks, only one trial, looks at pumping five times a day and they did this for 10 minutes after each feed until lactogenesis and this is in women with a BMI greater than 29. So in women they were worried about delayed onset of lactogenesis and they asked them to pump in addition to physiological feeds at the breast. And what they found there was really important was that breastfeeding durations, exclusive and ultimate breastfeeding durations, were actually shorter in the group that had been allocated to the pumping intervention in the early postpartum than in the control group who'd been left to normal care. So a small study, underpowered, the groups were not well matched at baseline. But I think it highlights a really important point about our potential interventions in this space was that actually we've got the potential to do harm if a programme is poorly executed or if it's overly burdensome for our women. So definitely not pumping. What about structured support programmes? I think that this really depends on the context. So there are a number of studies looking at this. Essentially they involve linking women of an elevated BMI up with breastfeeding support counsellors or with lactation consultants. There's a Danish one where there's quite good evidence for extended breastfeeding durations. There are several US ones with really disappointing outcomes, no evidence of benefit. I do think we should talk about metformin. And I probably touched on this last time. But metformin's theoretically really interesting, given the increasing evidence for the importance of insulin action to milk production, which we've already talked about.
So there's one little pilot RCT here. And again, it's by Laurie Nomsen Rivers Group. So she took women with insulin resistance. They had to have either central obesity or PCOS or a raised fasting glucose or a history of GDM. And small groups, small numbers, 10 allocated to metformin, five allocated to placebo. The key thing to realise here was that this was a pilot trial. It was done to assess the feasibility of an extended trial. They assigned these women to metformin explicitly for the purposes of seeing whether it would augment their supply. But they assigned them pretty late, about 36 days postpartum, probably after low supply was already established. And the upshot of this was that it was really a study marred by logistical concerns. A lot of the women found that collecting the milk volumes was too burdensome. Many of them stopped the metformin due to side effects. And somewhat unsurprisingly, the results of this really small trial weren't significant, although they did see a tiny trend towards increased milk supply in the metformin group in the vicinity of sort of 10 to 20 mils per 24 hours. And ultimately, they felt that this was not worth upscaling to a larger trial. So I think we've got insufficient evidence to suggest that metformin alone can augment milk supply in women with obesity and insulin resistance. Certainly when I see women who maybe have an indication for it. Otherwise, perhaps they're going back onto it after a type 2 diabetes pregnancy or for PCOS. I'll talk to them about the fact that it's probably creating a favourable overall metabolic environment for milk production. But I don't think we've got sufficient evidence to prescribe it primarily for the indication of augmenting milk supply in women with obesity. So I'm now going to move across to some suggestions really of a more pragmatic clinical nature that might be of more use for the individual sitting in front of you.
In the prenatal space, I think respectful care at every size is important. So talking about movement rather than exercise and talking about low inflammatory diet patterns or reduced processed foods, rather than terms like calories and portion sizes and using that person-centred language that I talked about. Evaluating breast size at the prenatal visit, looking for breasts that may be widely spaced or conical, suggestive of insufficient glandular tissue. Asking about previous breast reduction surgery, which might be common in this cohort and the approach there that was adopted, because that can have impacts on milk supply according to the specific surgical procedure. Identifying and sharing good local resources for nursing bras, for tops, for baby carriers that might accommodate larger bodies and meeting the woman where she's at. So saying to her, what have you heard about breastfeeding? Validating some concerns about milk supply is important. So some mothers with obesity make lots of milk, others make less. Talking about the fact that transition from colostrum to mature milk may be later than 72 hours and what might that look like in terms of options.
If we're expecting a large for gestational age impact or a large for gestational age infant, or if we're dealing with maternal diabetes, then we'll review the hypoglycemia monitoring protocols at our institution and get mum ready for the fact that baby's going to be tested for that. And we can certainly have discussions about antenatal expression. I've talked about this before. There's certainly evidence of its safety for women with diabetes and pregnancy and the DAME trial and the Lancet is the seminal paper there. But there's no evidence that it makes meaningful changes to long-term breastfeeding success and it's really a highly individual decision. In the immediate postpartum period, again, you will all be aware of this, the importance of immediate skin to skin, including for Caesar deliveries. And we've got Cochrane level meta-analysis evidence that this increases neonatal glucose levels, that it lengthens ultimate breastfeeding duration. Pragmatic positioning support for women in larger bodies, I think is really important. So some of these women may find that a lying back position's helpful or a football hold's helpful, or they may want to breastfeed in a reclined position. They may need a rolled up blanket or a small washcloth underneath the breast in order to efficiently elevate it to visualise attachment, or they may want to use a mirror for that. They may need to support or lift their breasts in order to stop it covering baby's mouth in order to allow baby to breathe and swallow, but important to keep the fingers away from the areola. And a properly fitted maternity bra is always really important too. The ABA has a really, I mean, you will all be aware of this, but they've got a really good wealth of breastfeeding information in general. But this page on breastfeeding with larger breasts, I particularly like for women with larger bodies. And in particular, about halfway down, there's a five minute video featuring a woman in a larger body along with two lactation consultants. And she talks about successful attachment and positioning in the context of her maternal obesity. So I think that is a really practical and unintimidating guide for patients and maybe a good resource to point them to to work through in their own time.
If we're faced with low supply, then as with all women with low supply, you may want to think about an endocrine workup for causes of true low supply. So that would be checking maternal thyroid function and prolactin levels. You may want to do an extended pituitary panel if you are worried about Sheehan syndrome and checking for retained placenta in the early weeks. Triple feeding as always needs to be advised with caution and for a time limited period, a few days followed by review around its ultimate sustainability. And it may be prudent to be open to partial or mixed feeding and to discuss the fact that that can be a really satisfying long term relationship. A few more practical tips. So you may encounter women who've had previous bariatric surgery and for them B12 is really, really important both in pregnancy and in the postpartum period. So particularly following those malabsorptive procedures, which we're possibly seeing less of now, but they are still around. So we're talking about bypass as opposed to a sleeve gastrectomy. B12 deficiency really, really common up to sort of two thirds of patients at three years following those procedures. And there are case reports of women who were born to post-bariatric surgery patients, infants born to post-bariatric surgery patients who ended up with profound cortical atrophy and infantile pancytopenia due to maternal B12 deficiency. So really, really important that if you're seeing someone who's got a history of bariatric surgery, that they have close follow up with their specialised bariatric dietician throughout pregnancy and also throughout lactation and that supplementation is adequate.
Weight and intentional weight loss [00:44:36.11]
Finally, I just wanted to touch on what I think is a really important topic and that's around intentional attempts at weight loss in the postpartum period in the context of lactation. So I talk about this a lot when I do postpartum follow up for my woman with GDM and I can imagine that it's something you also really frequently encounter in general practice, for example. I think it's important to acknowledge upfront that there are really strong social pressures around getting rid of gestational weight gain in the immediate postpartum and they probably affect even those of us who consider ourselves to be sceptical consumers of such content. So breastfeeding, what about breastfeeding? It's an energy expensive process. It's theoretically consumes about 500 kilocalories a day. Does it help with weight loss? Well, this is a contentious issue. Probably in the first three months postpartum, breastfeeding women, despite that excess caloric expenditure associated with the breastfeeding process, will subconsciously increase their calories and reduce their physical activity in order to meet the energy demands of lactation. Whereas out beyond three months, they're probably more likely to mobilize fat stores. But if you look at overall systematic reviews, looking at postpartum weight retention, according to lactation status, there's no clear relationship between weight loss in breastfeeding cohorts. And it's probably just because of the heterogeneity of the populations in those studies. The authors and the systematic reviews ultimately say things like, oh, there are lots of interrelated psychosocial and behavioral variables. And I think you'll be aware that in clinical practice, this just seems to be something that's really, really individual. There are some women that cannot keep weight on when they lactate.
There are some women that really struggle with weight gain during lactation. And overall, when you look at the population level, there's not a real clear direction there. Although certainly if we are seeing weight benefits, it's probably out beyond those first months of exclusive breastfeeding where we tend to be pretty good at meeting our needs. Postpartum weight loss, though, of 0.5 to a kilo a week when it's intentional is shown to not adversely impact on infant growth. And that sort of trajectory is considered safe. Really important to remember that lactation itself requires at least 210 grams of carb a day. So low carb or keto diets can theoretically precipitate lactation ketosis. And we need to avoid those in the postpartum period. We should talk a little bit about lactation ketosis because I think it's really interesting. So this was initially described in the vet literature around more than 100 years ago.
And typically in the veterinary context, it will occur in postpartum cows when they're unable to maintain sufficient energy intake and hepatic gluconeogenesis to meet the substrate demands of lactation. And they become hypoglycemic and hypoinsulinemic. So they have low circulating glucose levels and low circulating insulin levels. And that means they break down their fat tissue and ketone bodies form. The treatment for cows is IV glucose. Now, in women, in lactating human women, lactation is also a hypoglycemic hypoinsulinemic state. But we tend to be a little bit more resistant to frank ketosis. In saying that, there are a handful of cases in the human literature of lactation ketosis in women. And it generally presents pretty similar to diabetic ketoacidosis, DKA. So nausea, vomiting, an increased anion gas acidosis, blood ketones are up, urine ketones are up. And most of the case reports are in women who are lactating with, for some reason or other, restricted access to carbs. So there are a few case reports of keto diets. There are a few women who are doing religious fasting or severely unwell with something else. Or perhaps they had increased and or they had increased lactation demands, for example, a twin lactation and just couldn't keep up with the carbohydrate demand. And the treatment similarly is IV fluids and adequate carbs. But I think this is a real, it's an important thing to have in mind when you're thinking about the kind of dietary recommendations we want to be making to women who are intentionally trying to lose weight in the postpartum period. So adequate carbohydrates are important.
I do want to talk about GLP-1 agonists, and I think this is really clinically relevant. There's huge global interest, you'll all be aware, in this class of agents. So obviously, they were initially licensed for the treatment of type 2 diabetes, but are initially and increasingly being prescribed for the treatment of obesity. And they're certainly the agent that I prescribe the most for medical management of the condition. I prescribe them a lot in women of reproductive age, particularly for women with PCOS, for women with insulin resistance. So this top picture here is Ozempic, which is semaglutide. And Ozempic, you'll be aware, is the brand which is licensed in Australia for type 2 diabetes, and it's got a ceiling dose of one milligram. And until fairly recently, that was being used off-label for obesity with the result of significant supply issues, which we really first faced over a couple of years. And now we will very much preserve this agent for the community with diabetes
In August of last year, we got Wegovy, same drug, semaglutide, but with a 2.4 milligram dose ceiling, and licensed specifically in Australia for weight management. So this is not on the PBS. It's between $260 and $460 a month, depending on the dose that you're requiring. It's got a multi-step dose up titration schedule from 0.25 up to 2.4 milligrams. And then we've also got Munjara or 2-zepatide. So this is a dual agonist, works on both GIP-1 and GLP-1 receptors, and it's got even better weight loss efficacy. So in conversations with patients, I'll typically say sort of 12% to 15% versus placebo for semaglutide versus 15% to 25% versus placebo for 2-zepatide. 2-zepatide or Munjara has been licensed for weight in Australia since September of last year. There are six doses in the up titrating dose regimens, and they now, they used to be until a few months ago that they were in a pen, a vial, an insulin vial with a syringe, which was, sorry, a vial with syringe, which was really fiddly for patients. But they're now available in these quick pens, very similar to these delivery mechanisms, high price points, $390 to $690 a month. So outside of the financial means of many patients, but certainly I do have patients on there. So all of these agents, GLP-1 agonists, just to remind you of the mechanism of action. So what they do is they enhance glucose dependent insulin secretion to improve glucose homeostasis. So in response to glucose arriving at the small intestine, they'll amplify the insulin release in response to a glucose load. And that's the mechanism by which they help with diabetes. They also slow gastric emptying, and that's the reason for them prompting satiety, but also causing constipation. And they also act directly at the level of the CNS. So increasing satiety and reducing energy intake. And they work at exactly that area we were talking about earlier, the arcuate nucleus and the hypothalamus with those AGRP and POMC pathways. And you'll see that GLP-1 and GIP receptors are present in the arcuate nucleus.
And so you'll hear patients talking colloquially about these agents switching off the food noise. So they have a multi-pronged mechanism of action. Smaglutide and lactation, really topical. So the Texas Tech University, which does the Infant Risk Call Center and the Infant Risk App, which many of you will use in clinical practice, they noticed an increase of over 500% in people ringing up asking about smaglutide safety during lactation just over the four-year period from 2021 to 2024. So massively topical issue. What do we know about the safety of smaglutide in lactation? Well, let's think about pregnancy first, because I think this is a lot more clear-cut. In pregnancy, we've definitely got evidence of potential teratogenicity. So in pregnant rats, offspring who are exposed to smaglutide have reduced growth, have increased skeletal and visceral malformations. Smaglutide-exposed monkeys have increased pregnancy losses and smaller offspring. And the advice universally in the prescribing information and all the major clinical guidelines is that we would discontinue these agents two to three months before actively trying to conceive. Lactation's a little bit different. It's a large molecule. Smaglutide's more than 99% protein bound. And so the amount entering breast milk is theoretically likely to be very low. Even if this agent entered milk, it's only 0.4 to 1% orally absorbed, which is why we have to give it an injected capacity for the most part. And therefore, it's theoretically really unlikely to adversely affect a breastfed infant.
But I suppose in typical fashion, the prescribing information is fairly risk-averse. And they say, look, in rat models, they found that there was smaglutide secreted into the milk or present in the breast milk of these rodents. And so you therefore can't rule out risk to a breastfed child. And they say, erring on the side of caution, that smaglutide should not be used during breastfeeding. When you look at the infant risk app, that's a little bit softer and they say it's probably compatible. Although they say caution is recommended until more data is available. With all of that in mind, I was delighted to see this study. I've been asked this question a lot and I've been following it with some interest. So this is the first and to my knowledge, the only actual pharmacokinetic study of smaglutide in breast milk. And it came out in August of last year. Again, from the team at Texas Tech who run that infant risk call centre and the infant risk app. And they justified this as being born out of an immediate clinical need for data so we can make some evidence-based decisions when we're treating our breastfeeding women for type 2 diabetes and for weight loss. Is it safe for them to take ozempic or smaglutide? And this is a simple, small number. It's a pharmacokinetic study. Eight women and they looked at smaglutide levels in the milk at 0, 12 and 24 hours following self-administration of smaglutide at the diabetes type doses. So between 0.25 milligrams and 1 milligram. And this is really encouraging. ND means not detected. So smaglutide was not detected in any of the breast milk samples. So it was below the levels, if it was present, it was below the levels of lower limits of detection of this highly sensitive LC-MS assay that they used. And the authors of the study concluded that these findings support the idea that the direct infant risk due to smaglutide in the milk is negligible and that fears concerning infant exposure to maternal smaglutide via breast milk are likely overestimated.
So this is really reassuring, I think. What I do harbour a lot more concern about, though, is simply the risks, the implications of rapid weight loss for a mother's supply and her milk quality, particularly in those really critical first few months postpartum. We all know that you need calories to make milk. And smaglutide markedly reduces food intake. That's how it works. And also to varying degrees, depending on the individual. So there is real potential for impact on milk supply. And I think also the impact on milk nutrient composition, particularly when a woman is exclusively breastfeeding. A lot of people experience nausea and vomiting and significantly reduced oral intake, which can influence their hydration status with further impacts on supply. And so my practice is that in the early postpartum, I'd recommend a much more gentle approach. So I'd say to these women, you've just made a human. It's time for gentle movement, for sustainable dietary changes and for support for broader considerations, mood, social connections, relationships.
The other thing to say here is that these medications are increasingly considered long term or indefinite. So we know that they have a good long term safety profile. We also know that when they are abruptly discontinued, that weight tends to go back on. So increasingly, we're prescribing them in an indefinite capacity, much like you'd start someone on a blood pressure tablet and you'd expect them to remain on it as long as they had hypertension, with the blood pressure likely to go up again when it was stopped. So as we're increasingly seeing them as indefinite, open ended prescriptions, I think there's no rush to recommence them in those precious postpartum months. I've put this QR code here because this is a really, really good article. Again, it's from the team behind the Infant Risk app that so many of us use for medication safety and pregnancy and lactation. And this article has really good info for mums about weight loss and lactation. It's got clear diet and exercise guidelines. It's actually got meal plans and snack ideas for lactating women. It's got a special calorie counter that they designed, which calculates a woman's basal metabolic rate and factors in the additional demands of her lactation, taking into account the baby's age and weight. And it also talks in appropriate consumer facing tones about some of the research that I've talked to today. So the safety profile of GLP-1 agonists and obesity, pharma and lactation.
And it also talks too about the importance of self-compassion in that critical postpartum period. So definitely refer women there. I think it's a really lovely resource. And this is my final slide. So obesity is a complex and chronic disease. We know that once an individual's lost weight, there are these really powerful hormonal and central mechanisms, not a lack of motivation, which will drive a near universal tendency to weight regain. We know that weight stigma is pervasive in our society and that as clinicians, we need to have a really careful and nuanced person first approach to treating these individuals.
We know that from a lactation perspective, obesity is associated with earlier breastfeeding cessation and lower rates of exclusive breastfeeding in the postpartum and that the underlying mechanisms fall into physiological, clinical and then psychosocial buckets. And then weight loss during lactation for all women is certainly possible and can be safe, but is ideally slow and ideally sustainable with caution around those pharmacological agents or overly restrictive diets, and particularly in that early postpartum period. I think things are a little bit different there when you're dealing with maybe someone breastfeeding a toddler. So that's all of my material. Really happy to take any questions.
Questions [01:02:50.08]
Participant 1: Hello, Kate. Thanks again for that presentation, which I was really fortunate to see twice after the breastfeeding conference last year. I don't know why my video isn't working on my laptop, but I'm here. And it was wonderful, obviously, even since September, how much more topical the pharmacotherapy has become with our increased access. So, I loved the expansion you put on the end there, because I've just put in the chat that I actually had someone raise it at like a six-week check not too long ago. And yeah, it just did not need to be her priority. But so many people's self-esteem and all sorts of things can be linked to it. So, that's wonderful. My question, which I put up a bit higher, isn't so relevant to the question of lactation. But regarding B12, I wondered if you've got any thoughts, or if this is usually done by someone else in your team, but regarding whether a bariatric surgery and B12, because so commonly I feel people have just fallen off from the bariatric team, and we're left, you know, two years later, they haven't had any blood. So, you sort of do them again. And I did have someone actually, which is great, because she's just come in today pregnant. But last year, she came in for a preconception check, and I think the total B12 was low. So, we supplemented, but the active came back, and it was normal. So, in retrospect, I wouldn't have necessarily boosted her, but she had been in the past. So, and, you know, I find it's a very evidence-free zone, particularly out of pregnancy. But do you have any guidelines on what we should be doing there?
Kate: I think what you've done is really sensible. I think if you're doing serum levels, and you're treating to those, I think you're absolutely, it's entirely defensible, and probably the way that I tend to go in clinical practice. Again, I think that the type of bariatric surgery is really important here. So, you know, 10, 15 years ago, we were seeing a lot of, there was a lot of these malabsorptive procedures. So, biliopancreatic diversions, gastric bypasses, whereas now the sleeve gastrectomy is much more the kind of the common, the standard approach to surgery, the restrictive procedures, rather than malabsorptive. And they are much less likely to cause the significant micronutrient deficiencies that we used to see. I think the other group, and moving entirely away from obesity, is the kind of increasing vegan, vegetarian. So, it's those groups that you think may be at risk of micronutrient deficiency. But I think checking a level is a really good first step, rather than moving into sort of routine supplementation. Yeah. And active B12 over the total, or would either sort of be an indication that it's dropping and it might be worse.
Participant 2: Well, I had a question, Kate. You mentioned the languaging that you use with patients. Yeah. I wondered if you could expand on that for us for a moment
Kate: Yeah, I think that's a really good thing to bring up. I have to say I'm very privileged in that I work in a referral centre where people are sent to me because they want to discuss weight. So you start from an advantaged standpoint there and that you're not having to broach the conversation. But I do think that that general principle around outside of that context, if you're seeing someone in a broader capacity and you think their weight is relevant to the conversation, I think that, do you mind if we talk about your weight? Are you happy to talk about your weight today? That's a really good, it's often touted, but I think it's a really good and sensitive way of broaching the topic. I also ask women if they want to be weighed. I have lots and lots of women who want blind weighs. And I say, many of my women want blind weighs. Would you like to have a look at the number on the scale? Because I think that normalising that is really important. And as I said, I don't use terms like obesity in conversation with patients. I tend to talk about carrying a little bit of extra weight or being in a higher BMI category. And I talk more, as I said, about movement, about a lower processed diet, moving away from convenience foods rather than those somewhat pejorative diet culture type terms around portion sizes, calories, exercise. It just helps to frame things slightly differently. I also think that you can tread too softly and that some women really want to discuss weight and they really want to decrement their weight. And that it is OK in those conversations to talk about a weight loss goal and to talk about pharmacotherapy, because that is absolutely what some women want. So it really is about meeting each woman where she is.
Participant 3: Can I ask one that's a little bit of a tangent, Kate, but what's your view on the role of things like the GLP-1 drugs for women planning a pregnancy?
Kate: Good question. I prescribe them all the time in that capacity, but not in the immediate pre-conception context. So I have lots and lots of women for example, I do a lot of PCOS and have lots and lots of women who are significantly overweight and wanting to optimise their health for conception. And I think a GLP-1 agonist is really, really good in that context, particularly if you've got sort of 18 months, two years of headway. And I'll talk to them about the fact that this needs a two to three month period of washout prior to a planned conception, but it can really improve fertility, particularly if you have someone who's on an oligoanovulatory, maybe she's 100 kilograms and she's only getting two or three periods a year, you get her down to 75 kilograms with semaglutide as we govy, for example, over a two year period, her menstrual cycles resume and she's fertile again and can conceive. So that's a clinical scenario that I would counter every single day. So I think they have a really good role in the pre-conception context, but probably not the immediate pre-conception context. So if that woman at 100 kilograms comes to me wanting to be pregnant next week, we talk about the fact that this is probably not the ideal option, that we need to refer her for some fertility input and optimize her diet at the weight that she's at. So it really comes down to what sort of term that you're looking at. I have some colleagues, saccenda or araglutide has a shorter half-life. And so when we used to use that more, I would sometimes switch women if they got their weight down on a weekly GLP1 they were really wanting to maintain, I would sometimes switch them over for a short period of time to daily saccenda just because it has a shorter washout period and you could potentially take that, you know, you could have a washout of two weeks for that before trying to conceive. I have to say I do that less nowadays just because I don't use that agent so much, but that's theoretically something you could do. But I am quite strict about emphasizing effective contraception whilst on a weekly GLP1 and make sure that women are using effective contraception. In saying that, you'll hear, you'll be reading things in the mainstream media about ozempic babies and there is certainly women who fall pregnant unintentionally whilst taking these and obviously the advice is just to stop them as soon as pregnancy is recognized.
Participant: Kate, are you aware if anyone's following that cohort to actively look for any risks? Clearly there's a group who are conceiving unintentionally.
Kate: There are definitely a group and I think in an ideal world we'd probably be reporting those to drug companies for surveillance. I'm not sure of what that looks like. If they're actually doing it, I know. It would be ideal, wouldn't it? My understanding is Mothersafe in New South Wales is collecting some data on nosympic exposures.
Participant: So then my next question, and you may be able to update me on this, Kate. The last time I went looking, the concept of a prolactin receptor was still a kind of theoretical framing, but there was no actual prolactin receptor that we'd been able to identify in the research literature. Am I right there? Do you have any updates on that?
Kate: Yeah, I think certainly most of the literature that I'm reading about is referring to prolactin receptors as a discrete entity. Yeah, that's okay. It just interests me. At one point, it might have been a couple of years ago now, I was looking into it and really it seemed as though there was no actual locatable. Well, there are certainly lots of different hormones that can act at prolactin receptors. For example, human placental lactogen and human growth hormone will have a degree of affinity for the receptor. So it's often, as is often the case with hormones, that there's a baseline receptor that has a stronger affinity for one molecule than another with conformational changes. But certainly if it's, I think it's probably with a lot of these things, they're complex proteins that we simplify down to call them things like prolactin receptors, whereas in actual fact, they have a stronger affinity for one molecule than another. Thank you. Are there any more questions for Kate? I just had one a bit more about the metformin and it sounds like there's not any really good studies on metformin and milk supply. So is it a reasonable thing for women to ask to be on metformin? Yes. So I think metformin is definitely safe in lactation. In fact, the mainstay of diabetes management during lactation is metformin and insulin really, and due to the dearth of safety data around our newer agents. And so the safety is well established and I think we can certainly say that to women. I think there's a really strong theoretical basis by which metformin as an insulin sensitizer could theoretically help to augment milk supply by enhancing those insulin receptor interactions at the level of the lacticide. I just think that we haven't got enough hard clinical evidence in RCT format to start particularly prescribing it for the indication of boosting milk supply. In saying that if I've got a woman who is contemplating going back on it for type 2 diabetes or for PCOS and they are lactating, I would certainly say that yes, mechanistically, this is conducive to a more insulin sensitive environment. And we think that that probably will benefit on lactation, but we just don't have the clinical evidence to back it up. I am aware of it being used off label in some protocols specifically for the purposes of augmenting milk supply, particularly when all other routes have failed. And I think that that will be safe. I just don't think that we have sufficient evidence to say that it's effective. Doesn't mean it's not, just means the research hasn't been done.
Pam: I want to thank Kate for such an important presentation, actually, for those of us who really care about breastfeeding and lactation. What you presented tonight is so clear. It's profoundly clinical relevant to those of us working in this space. And I also really enjoy the way you present the research, the way your mind engages the research analytically. It's really clear, profoundly evidence based, actually, or at least a very clear analysis of when we don't have the evidence as well and when we're looking at theoretical models, which is just tremendously refreshing. So really, I find your presentation superb, Kate, and I know that those participating in the NDC Institute also do. So thank you once again for being so generous with your time. And we really look forward to you coming back to talk to us in May on oestrogen bones and breastfeeding.