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Episode 70: Improving Perinatal and Trans-Generational Health with Functional Medicine

Improving Perinatal and Trans-Generational Health with Functional Medicine

Improving Perinatal and Trans-Generational Health with Functional Medicine

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Improving Perinatal and Trans-Generational Health with Functional Medicine

With Emily Rydbom, CN, BCHN, CNP, and Leslie P. Stone, MD, IFM-CP

Some of the most extraordinary work happening in medicine right now comes from the GrowBaby team of Leslie Stone, MD and her daughter, Emily Rydbom, CNS. In their mostly Medicaid model, they’ve adopted a systems approach to pregnancy, and thereby doing so, have remarkably improved outcomes.

Their rates of autism, eczema, ADHD, premature labor, gestational diabetes and pregnancy-induced hypertension fall well, well below national averages. Learn about their unique program and outcome studies in this episode of New Frontiers.

Of all the podcasts I’ve conducted over the years, this one hit home and is the most life-changing. Take a listen, be sure to review and rate us on iTunes or wherever you listen to New Frontiers, and as always, I so appreciate your time and energy! ~DrKF

Summary - Improving Perinatal and Trans-Generational Health with Functional Medicine

Using functional medicine strategies to support optimal health is important for everyone, but it is especially critical to bring a functional medicine lens to patient care during pregnancy.

Research suggests that targeted, sequential interventions during different time periods of pregnancy can have short- and long-term impacts on the health of the baby.

In this podcast, Dr. Fitzgerald talks with Dr. Leslie Stone, who is board certified in family practice and completed a fellowship in surgical obstetrics, and Emily Rydbom, a certified nutrition consultant, board certified holistic nutritionist, and certified nutrition professional. Together, these women lead GrowBaby Health, which works with women to improve perinatal and trans-generational health.

In this New Frontiers in Functional Medicine Perinatal podcast, you’ll hear:

  • Understanding and identifying the four different birth phenotypes
  • Birth phenotypes and their long-term correlation with chronic diseases
  • Epigenetics of birth outcomes
  • How events during different stages of preconception and gestation effect infant and long-term health
  • Benefits of working with patients in a group model
  • Working within the insurance model, specifically Medicaid
  • How emphasizing a food-first approach can increase patient compliance
  • How maternal stress effects fetal development and birth phenotype depending on the trimester in which it is experienced
  • The most helpful tests that insurance will cover
  • How small and simple interventions, such as listening to music, can have a powerful impact on the fetus in utero and long-term health outcomes
  • How experiences in childhood and early life dictate physiological stress response later in life
  • How high stress in males can trigger micro-RNA changes in their sperm
  • Benefits of DHA supplements in the second and third trimester
  • Whole food strategies for decreasing the likelihood of preterm birth
  • Rapid epigenetic modification capabilities of specific diets
  • Different active processes during each trimester (methylation during first trimester, interconnectedness of organ systems in second trimester, etc.)

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Leslie P. Stone, M.D., IFM-CP

Leslie P. Stone, M.D., IFM-CP, Board Certified in Family Practice, with a fellowship in surgical obstetrics. She is an International lecturer on developmental programming of disease and application of individualized functional medicine care during pregnancy.

Her passion is helping parents capture the miraculous during pregnancy by changing habits, their lives and empowering life in and out of the womb. She has been delivering babies since 1982 and has delivered nearly 5000 children. She is owner of Ashland Comprehensive Family Medicine Stone Medical in Ashland, Oregon where she continues to practice.

Her undergraduate degree was from Washington State University in Physiological Psychiatry was followed by her MD from University of Washington Seattle, Internship in OB/GYN Oregon Health Sciences University, Residency at UCLA in Family Medicine, Surgical Obstetric Fellowship at UCLA Ventura and further Certification in Functional Medicine.

Dr. Leslie Stone and Emily Rydbom are co-authoring a book and look forward to its release in 2019.

Emily Rydbom, CN, BCHN, CNP

Emily Rydbom, CN, BCHN, CNP is a Certified Nutrition Consultant, Board Certified Holistic Nutritionist, and Certified Nutrition Professional. She has been practicing the functional nutrition approach to pregnancy since 2010 and is an International lecturer on practice implementation to improve perinatal and transgenerational health.

She co-published the study, “Customized Nutritional Enhancement for Pregnant Women Appears to Lower Incidence of Common Maternal and Neonatal Complications” printed in – Global Advances in Health and Medicine with Dr. Leslie Stone and others. She has an active clinical practice, working beside Dr. Stone, helping women reach their nutrition and pregnancy health goals.

Her passions include empowering women during the preconception, pregnancy, and postnatal time period, and teaching families about healthy nutrition and lifestyle balance from 6 months-5+ years.

Her undergraduate degree was completed at Southern Oregon University followed by her postgraduate training through Bauman College-Berkeley, California. Dr. Leslie Stone and Emily Rydbom are co-authoring a book and look forward to its release in 2019.

The Full Transcript - Improving Perinatal and Trans-Generational Health with Functional Medicine

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine, and today is no exception. As usual, I am extremely excited about my next guests. I’m talking to Dr. Leslie Stone and Emily Rydbom, her daughter. They are two amazing women doing remarkable work in the functional medicine space out in Ashland, Oregon. So, let me give a little bit about them and we will jump in.

Leslie Stone is an MD, IFMCP, so IFM certified. She’s a board certified in family practice, and she completed a fellowship in surgical obstetrics. She’s an international lecturer on developmental programming of disease and application of individualized functional medicine care during pregnancy. Her passion is helping parents capture the miraculous during pregnancy by changing habits, their lives, and empowering life in and out of the womb. I love that. She has been delivering babies since 1982 and has delivered nearly five thousand children. She, so Dr. Stone, with Emily, her daughter, are coauthoring a book and look forward to its release this year. We’re going to pick their brains on the book and all sorts of things.

Let me tell you a little about Emily. She’s a certified nutrition consultant, board certified holistic nutritionist, and certified nutrition professional. She’s been practicing the functional nutrition approach to pregnancy since 2010, and is also an international lecturer on practice implementation to improve perinatal and trans-generational health. We’re going to talk about trans-generational today, too. She co-published the study Customized Nutritional Enhancement for Pregnant Women Appears to Lower Incidents of Common Maternal and Neonatal Complications. This was published in Global Advances in Health and Medicine with Dr. Stone and others. She’s got an active practice alongside Leslie just helping women reach their nutrition and pregnancy health goals. Again, just welcome, welcome, welcome to New Frontiers Dr. Stone and Emily.

Dr. Leslie Stone: Thank you.

Emily Rydbom: Grateful and happy to be here.

Dr. Leslie Stone: Yes.

Dr. Kara Fitzgerald: So, I have been in awe of these women for years. I’m just big fans of their careful and extraordinary work that they’re doing over in Ashland, and well, the big thing that they’ve evolved, sort of the umbrella under which this beautiful work that they’re doing falls, is called Grow Baby. So, Leslie and Emily, I just want you to walk us through what Grow Baby is, and just talk about the genesis of it.

Dr. Leslie Stone: Well, so I’ll start out. This is Leslie, and what Grow Baby is, is our way of approaching pregnancy and the preconception time period. What that means is we take what OB providers, women’s health providers, have been taught, and add to it this functional medicine or systems biology overlay. It recognizes nutrient insufficiencies and deficiencies. It recognizes genetic vulnerabilities. It recognizes toxic vulnerabilities, and puts that all together in a preconception, trimester by trimester, and post-partum program platform, quite robust, that takes women, identifies them individually, targets their needs in that robust, 360 functional medicine sort of way, and then follows them through their pregnancy, and comes out with remarkable outcomes.

Dr. Kara Fitzgerald: Yeah. It’s beautiful. We’ll print a link. We’ll have a link on the study that you published on the show notes, folks, and then we’ll talk about some of those outcomes here later on. We’ll also put links to Grow Baby, because it’s a whole site. You’ve got a lot of activity going on over there. Is that true?

Dr. Leslie Stone: Yes. Absolutely.

Emily Rydbom: Particularly in the social media platform. 

Dr. Kara Fitzgerald: Yes, okay, so talk to me about the hybrid MD nutritionist implementation model in pregnancy, and I guess drill down a little bit deeper into this Grow Baby model that you’ve just outlined.

Dr. Leslie Stone: Well, I think maybe I’m going to start this one off too, because it has very much to do with the genesis of this Grow Baby thinking. What that means is after you’ve been in practice as long as I have been, you see that despite all the individual step-by-step, single variant manipulations of pregnancy and management in the prenatal time period, not work for you in terms of improving the maternal, common maternal morbidities, and any of the outcomes.

I realize that most of the standard of care that we provide is great. It does a fabulous job, but what about the unchanging morbidities and mortalities that are associated with the mother? The pregnancy-induced hypertension? The gestational diabetes? Then what about those baby outcomes? The ones where the babies are too big or too small, and too early? Or too stressed? Those variables, those outcomes, despite the best standard of care, were not making any difference. Single nutrient intervention, single lifestyle interventions, were not budging the needle on anything.

Dr. Kara Fitzgerald: Single nutrient interventions like a prenatal vitamin or a little bit of folate?

Dr. Leslie Stone: Exactly. Certainly they do give us, as we all know… The story on folic acid supplementation. Folic acid does reduce neural tube defects.

Dr. Kara Fitzgerald: Yes. 

Dr. Leslie Stone: We know there are benefits to these individual nutrient interventions and lifestyle interventions, but it really wasn’t budging the needle on other outcomes, particularly the [inaudible 00:06:36] outcomes. We didn’t realize the importance of that until we realized, through this recognition that a concept called development programming of health and disease, that David Barker, way back in the 1980s, was doing epidemiologic work for the starvation time period during World War II when the Netherlands were annexed, and recognized at that time that depending on the trimester of restriction of pregnancy during that terrible winter, that would determine the frequency of the chronic diseases in those babies who had been born during that time period as 65-year-olds.

Dr. Kara Fitzgerald: That’s extraordinary.

Dr. Leslie Stone: It is extraordinary. Then we found that this data was recapitulated in Finland, in China, and there are some African studies and well in the Gambia that support mechanistically what is probably happening, in terms of that seasonal or restriction of nutrients. With that understanding that with additional understanding, and more robust research, we now know that those restrictions predict these birth phenotypes, and these birth phenotypes that we’ll review thoroughly, are the things that predict who’s going to be at the highest risk for our chronic diseases.

Given those vulnerabilities that we’ll also review very thoroughly that we know that without recognizing those vulnerabilities and meeting those needs or excesses individually in a targeted manner, that is the magic in the sauce. That is how we get movement and improvement in our birth outcomes, and it limits not just to that F1 generation, but there is mounting evidence that these all… Yeah, this is a process, often epigenetically driven, that recapitulates in the subsequent generations.

Dr. Kara Fitzgerald: That’s outrageously extraordinary. 

Dr. Leslie Stone: It is outrageously extraordinary, and it’s our belief that this is what is driving our chronic global epidemics.

Dr. Kara Fitzgerald: Yeah, that’s just outrageously extraordinary. Okay, I’m going to try to kind of summarize and just unpack a little bit, and you will correct me and flesh out anything, and then we’ll move on. And this is the genesis of Grow Baby, so basically what you have done, this extraordinary feat that you just basically unpacked to me, is that… You’ve delivered thousands of babies, Emily you’ve been in the space working with nutrition and pregnancy for, going on a decade now. So you’ve been in this space for a long time, and I know you pay tip-top attention to the science. I know that about you, and at some point, you began to tease out the development…Well, I guess you came across the Dutch hunger winter, so that period in the Netherlands when the Germans cut them off from food during World War II, and then they’d very carefully tracked subsequent generations and health outcomes.

And so, the first “aha” that you’re talking about is that they realized, depending on the trimester of the pregnancy during that starvation period, could be associated with different health outcomes that don’t present until much later in life, and these late in life presentations of this early exposure. This in utero exposure is what you believe to be driving the chronic disease epidemic here in the West, is that true?

Dr. Leslie Stone: And the globe.

Emily Rydbom: And the globe.

Dr. Kara Fitzgerald: And the globe, okay. And you talk about Gambia, and you’re talking about other places where they’ve done this careful tracking of subsequent generations, and there’s what you said Leslie, it’s either it’s a feast and famine. So it’s not just the starvation exposure in utero, but it’s an overabundance of foods or certain foods in utero that results in these outcomes. And, you’ve actually then taken the additional steps to begin to tease out what’s happening in a given trimester, and in that, you’ve developed these phenotypes. And that is the Grow Baby platform, am I correct?

Emily Rydbom: Yes.

Dr. Leslie Stone: Yes, I think that that’s exactly so.

Dr. Kara Fitzgerald: Okay.

Dr. Leslie Stone: It was also a recognition that in the midst of our Standard American Diet, which you would think would have more commonly macro- and micro- nutritional excesses, right? Did you know that that was not the case. That even in interrogating our population, we’ve found that we might have macro nutrient excesses in terms of fats, but we’ve found that, very often, their protein requirement was not being met. In addition, when we started interrogating micronutrients, and we were specifically aiming at those ones that were recognized to have a developmental programming impact, who were most active in terms of enzymatic activities for protein synthesis activities, that those were the ones that we were looking at to see if they were going to be insufficient. Sure enough, the remarkable overlap between specific micronutrients and those that derive resilience in health were really remarkably common in our population, which is a fairly educated, no food deserts. 

Dr. Kara Fitzgerald: Yeah.

Dr. Leslie Stone: And here we were, programming our diseases.

Dr. Kara Fitzgerald: That’s amazing, just extraordinary. All right, so we’re going to come back to that, because I know people want to know specifics as much as possible, as much as we can in this time. Again, I want to imagine folks, they have a book coming out. Yay. And you can hop over to their platform and see what they’re doing. We will just pack as much detail onto the show notes as possible. I do want to just point out – I want to say one more time, and Leslie, that the science is coming out of this developmental origins of health and disease paradigm. Or I guess it’s a professional association, and there was an international society for this.

Dr. Leslie Stone: Yeah.

Dr. Kara Fitzgerald: Okay, we’ll put links on it. We’ll put links on the website for that, and these folks are tracking this trans-generational… Tell me what they’re doing exactly, and then we’ll move on. Give me a nutshell of this.

Dr. Leslie Stone: What we found in the remarkably fast growing information that is accumulating in this field, is that we have just been finding more reinforcement for these nutrient excesses and nutrient deficiencies driving these four birth phenotypes, that drive the chronic disease… What we don’t see in that platform is an application. That is what stands alone for Grow Baby.

Dr. Kara Fitzgerald: Just extraordinary, wow. So we look at functional medicine as being the clinical application of systems medicine, and so Grow Baby is the clinical application of this DOHAD understudy. 

Dr. Leslie Stone: Yes.

Dr. Kara Fitzgerald: Ah, beautiful. Okay, so what’s next. Do you want to talk about the MD nutritionist implementation or describe the phenotypes? Take us…

Dr. Leslie Stone: Let’s do that one first, because this is a boatload of information as you can imagine, and a large part of the implementation piece, which is where Emily is so integral. Emily, as a nutritionist lifestyle group dynamic educator means that for the person who is engaged in providing obstetric or perinatal care, they are stuck pretty much in terms of reimbursement into this standard of care model. Which is good, it’s great, but it does not appear to be enough, and so, enter a well-trained nutritionist. And actually, Emily I would say has been responsible for the largest piece of this implementation, that what has been developed is a group trimester by price medical model that allows all of this information to be presented to the patient. Reinforced at the individual visits that people come to for the provider, but then they develop a group dynamic. They learn in general what are the right emphases during each trimester, and then they have the opportunity to drill down and individuate what sort of nutrients needs they might have specifically. And then, within this development, are several specific food plans that are based on a low glycemic anti-inflammatory diet, but are individuated to when we find the nutrient needs or specific diagnoses. 

Dr. Kara Fitzgerald: Mm-hmm (affirmative).

Dr. Leslie Stone: What we applied to mitigate their vulnerabilities. And so, that piece. That crucial piece. That crucial extension, amplification and application, as well as development of a group dynamic that is so empowering, the piece of the magic sauce is that these women now are trained and can take over. They are empowered to do their health. They know what to do now, and they choose how they are going to go back and [inaudible 00:17:18].

Dr. Kara Fitzgerald: So, I want to underscore and kind of scream from the rafters for folks. You’re operating in an insurance model. 

Dr. Leslie Stone: That’s right.

Dr. Kara Fitzgerald: So, this is the extraordinary thing, and so, when you’re doing group visits Emily, it’s by necessity, because you’re in the insurance model, and yet it has by design become this extraordinary kind of supportive, life affirming process, where that’s better than a one on one approach.

Emily Rydbom: It is, and the reason is, is I think there’s lots of data that suggests giving people in a group setting provides healing anyways, and so you direct that group in a way that empowers them and gives them life style interventions and doable interventions in their day, and all of a sudden, it takes on a life of not only healing, but of this concept that you can promote resilience and change health versus just decrease the risk of disease. I realize that’s a psychological game that we’re playing, but it’s an important one to say, because I think in general, if you look at our society, and you discuss what you can and can’t do in pregnancy, it’s overwhelmingly fear-based. It’s overwhelmingly in the known world. It’s overwhelmingly in the cant’s and shouldn’t’s, so we have flipped that script on its head a little bit, and have tested that throughout the course of the last almost decade, and not only do we see consistent results. They’re durable, and they have been sustained. We continue to see improving outcomes throughout the course of approaching it this way, and really, what I so appreciate about our physiology, is there’s redundancy within it, and these mechanisms that make our body go.

And so, in terms of just going down to the nitty-gritty format of these trimester-by-trimester classes. These food plans and this information is based first and foremost on just stationary development. We literally took that chart that everybody can access that says what happens in the first trimester through organogenesis and cellular differentiation and proliferation and neuro-development as we continue to move through, and we just formatted these classes and these food plans to meet those nutrient co-factors in food-form first. Because, what we have also recognized, is that, when we discuss interventions in accessible ways, such as through food versus through a really expensive supplementation or in this unattainable access that, it changes the way that people feel like they can apply this information. And so, just down to basic formatting, it’s so simple and unbelievably effective. 

Dr. Kara Fitzgerald: Doable.

Emily Rydbom: Yeah, it’s doable. And, I would have to say, it’s not just a nutrition focus, because it’s one leg of that stool of life style intervention that seems to be powerful, we move very much into the individualization of how somebody physiologically responds to stress and how we manage that stress and how we manage movement for that person and relaxation that doesn’t involve a screen. Communication with the relationships that we have with people. We definitely dive deep into each person as they sit in the class together, and they show each other successes and their vulnerabilities, and they attach to each other through this process as well. 

Dr. Kara Fitzgerald: Mm-hmm (affirmative). Wow. It’s really extraordinary and I know people are thinking about how they can learn what you’re doing. Clearly you’re going to need to train in this at some point so other clinicians can begin to enact what you’re doing in their practice, is that on your agenda?

Emily Rydbom: It is. It is absolutely being developed.

Dr. Kara Fitzgerald: Okay.

Emily Rydbom: Because people recognize that if we could clone ourselves, we would, but we also understand that this way of thinking has to be culturally specific and location specific, and we are not the most appropriate people to give this information to every single population. So if we can train these concepts and then the information can be applied on the ground individually, then that’s when we’re going to see change. We’re going to see that profound impact.

Dr. Kara Fitzgerald: And you’re working in not just a private insurance, you’re working with Medicare, correct? Or Medicaid. 

Emily Rydbom: That’s exactly, yes. So I think that is what is also so profound about what we do, is we see these results and we see these changes within a 50% Medicaid population. 

Dr. Kara Fitzgerald: Yeah. 

Emily Rydbom: Yeah, so, and…

Dr. Kara Fitzgerald: I’m taking a moment. Because we spend a lot of time in functional medicine scratching our heads around how do we do this in the population, which not only are you doing it in, manifesting it in, but you’re succeeding in this extraordinary way. So go ahead and finish that thought.

Emily Rydbom: No, and I think it’s important to say that we are seeing these results in the population that matches the vulnerability of our country. We have obesity, and we’re applying this with the same obesity rates as our country. With the same smoking rates as our country, alcohol use. Actually, in fact with even higher drug use than our country, and we’re seeing this shift. And so, I think for Leslie and I, this was not an option to opt out of this population. It was a moral prerogative, and ethical prerogative of ours to figure out how to meet these needs at the basic, most base level, and that’s to everyone. Not to only those who can afford it or who can access it. 

Dr. Leslie Stone: We didn’t want to increase social and economic disparity. .

Emily Rydbom: Right.

Dr. Kara Fitzgerald: Yeah, that’s extraordinary. And so, I guess maybe folks might be thinking a little about what labs might you do, and so forth. I don’t want to go into a lot of detail here because we’ve got a lot of other things to cover, but you’re basically doing things that people can get within the insurance or Medicaid, right? 

Dr. Leslie Stone: That’s exactly right.

Emily Rydbom: Right.

Dr. Leslie Stone: So we start with the standard history and physical that everybody does with those additional systems-based kinds of questions, and then an exam that is typical but also looks carefully for what might be that nutritional physical exam. What are the findings? And then we add to that the standard-of-care labs, which at this point only includes iron in terms of its nutritional exploration. But we add to it the most common ones that we can get paid for, which, common deficiencies that you can get paid for that have the maximal benefit we believe, which is Zinc, Carnitine-D, and Iron in the forms of the CBC. We make epidemiological assumptions about deficiencies in Magnesium and essential fats, and some imbalances in microbiome, because we have good epidemiologic data that suggested, and it’s just unwieldy in our insurance model to be able to get that.

So, we target depending on history and pre-history. Because driving this whole equation is what their parents were like, what their birth story was like, so we get that very thoroughly targeted, and then with our nutrition physical exam, as well as nutrient evaluations, we can pretty much target where their needs are. We’ve identified the vulnerabilities, we look at their toxic exposures, we identify those excess needs and then we give them a broad base that covers most people in terms of that nutritional base, lifestyle base, and then overarch that with targeted supplementation. 

In fact, for most of our population we can’t reach those needs in that short time period, but we can with some additional targeted supplementation. 

Dr. Kara Fitzgerald: Zinc, are you doing serum or red blood cell?

Dr. Leslie Stone: We are doing serum, because they have to be covered…

Dr. Kara Fitzgerald: Right.

Dr. Leslie Stone: …accessible, and doable.

Dr. Kara Fitzgerald: Yes. And I know that you’re doing a nutrition physical exam, which is extremely helpful. Yeah, all right so, let’s keep going here. Anything else you want to talk about regarding the developmental origins of health and disease, or do you want to move into birth phenotypes? 

Emily Rydbom: I think they work in tandem with each other.

Dr. Kara Fitzgerald: Right, go ahead.

Emily Rydbom: Defining birth phenotypes would be a good right place to start. And then also the two maternal morbidities which informed those birth phenotypes as well.

So, identifying the birth phenotypes. In layman’s terms, there’s too large, too small, too early, too stressed. There’s large for gestational age, small for gestational age, preterm birth, and then what we have coined as a term is a stress dysregulation phenotype. And so, its for those mothers who move through pregnancy with unmanaged stress, and then what are the effects of that stress response in utero to that fetus. And then the two maternal morbidities that we are looking to change outcomes are the two most common, which is pregnancy induced hypertension, and gestational diabetes mellitus. 

Dr. Leslie Stone: And those are the drivers for those birth phenotypes commonly. If you have complications from PIH, Pregnancy Induced Hypertension, or GBM, Gestational Diabetes, then they are more likely to be delivering preterm. They are more likely to be, in most cases. They are more likely to have, in the hypertension case, more likely to be too small. In the diabetes case, too big. In any of these cases, too stressed. 

Dr. Kara Fitzgerald: Well, talk to me about what that looks like. So the fourth birth phenotype that you’ve identified, the stress exposure, which is huge. Especially, I would imagine in your population, where you’re seeing a higher amount of Medicare and perhaps drug users or former drug users, and just some stress going on. 

Dr. Leslie Stone: This reveals itself. This too stressed phenotype reveals itself most effectively in looking at the cognitive and neuro cognitive function of that baby. It also shows up when they do imaging, like MRI imaging of brains, and they look at mothers who have had significant stressors. Particularly in the second trimester. They are particularly vulnerable in that second trimester. And then they look at that too stressed phenotype in terms of, what is MRI imaging looking at for the sizes of different parts of the brain, as well as the interconnectivity between the executive functioning parts of the brain, and those that are a little bit more primitive. The amygdala, and the limbic system, and they find distinct differences.

They also look at… so that’s the anatomic piece of it. They also look at the physiology that they look at babies offspring, like cortisol levels, and not just the cortisol levels but their cortisol response to stress in the neonate, and then on through, they have a prospect of studies as long as into the mid- to late- twenties. Each of these pieces of dysregulation prove to be durable, so if you are born with a cortisol dysregulation, you keep it. And it is associated directly with increased rates of anxiety in female offspring, and depression in male offspring. Slight increased risk for schizophrenia, and certainly delayed and impaired different types of memory. Language development. And then going back to the anatomy piece, those gray matter cortex remains thinner, and they even have a retrospective study that shows for seventy five year olds, increased rates of dementia, associated with a thinner cortex, they were more, in this case, too small.

Dr. Kara Fitzgerald: Now are they able to actually associate it with strictly in utero exposures, or is it early life exposures also?

Dr. Leslie Stone: So what they do, is they always… Our phenotype is the composite, right? But no, they extract that and extracted that, yeah. 

Here’s the other piece of this. So, that would sound hopeless, right? People; however, small interventions, very small interventions during that particularly significant time period, that second trimester, is not taking away the stressors, but doing interventions with movement. With music. With touch. The data that we have now said that cortisol dysregulation in the neonate, the failure of the cortisol to have the diurnal shifting is taken away. 

Dr. Kara Fitzgerald: That’s amazing.

Dr. Leslie Stone: It is amazing.

Dr. Kara Fitzgerald: It’s just really extraordinary.

Dr. Leslie Stone: One of the studies that I think best exemplifies this, is something so simple. They took women in their second trimester, and this is more directly during the second trimester of measurement, but what they did is they had them put their hands on their tummy, and listen to fifteen minutes of their favorite music, and they tested before and after, the blood pressure within the placenta. So the umbilical cord, in the middle cerebral artery, and in the umbilical cord the blood pressures there, the diastolic and systolic ratios, and they found them changed within fifteen minutes. They dropped the blood pressure. Which, that is what we think is one of the underlying mechanisms of being too small and too stressed, right?

Dr. Kara Fitzgerald: Mm-hmm (affirmative).

Dr. Leslie Stone: Fifteen minutes. 

Dr. Kara Fitzgerald: Amazing. I just want to say folks, Leslie talked about this in the beginning where when she talks about this lasting effect into years down the line of some of this early stress exposure, this is epigenetic changes. That’s what make it so resilient. It’s also interesting why we can actually turn it around relatively quickly at the right time point, so listening to music in the second trimester… And I want to just say for, maybe we’ll put the links on our show notes, but I have a podcast on here with Moshe Szyf, who’s one of the premier epigeneticists, who actually started unpacking what Leslie and Emily are now applying in clinical practice. 

So he started looking at this in the animal model, this whole stress response, and he’s looking at it in humans now as well. So that’s a podcast you can listen to and get kind of a drill down on the granular details of what they’re bringing into clinical practice, it’s just remarkable. Randy Jirtle is another epigeneticist who’s dealing in an animal model in an arena that Leslie and Emily are now transferring in the human world. So, we’ll put those links there. 

Emily Rydbom: And I think it’s important to say too, that it is imperative that we start turning our attention to how we manage that stress better. Particularly as we’re seeing rates of things like average childhood experiences with, it is estimated that over 60% of Americans have a high ACEs score of over four, and of that, a majority of them are women with ACEs score of over five. Overwhelmingly it’s women over men who have those high ACE scores, and so it’s not just “Did you experience a natural disaster, did you experience the death of a loved one?”, it’s also the experience that you have had growing up until that point in the preconception time period and now pregnant time period, it’s that what was your experience as a child and in your early parts of life that are now dictating your physiological stress response here, and then can we change that outcome by managing it appropriately with the right support system that is consistent and continual and ever changing as you individually need that to be changed. 

That’s why this MB nutritionist model is so important, is because it’s this team approach and this team care that allows us to have a more whole view and picture of every person who’s coming to us. Because that prevalency rate is just skyrocketing in this country, we have to turn our attention to that. And we’re seeing that manifest further down the road for our adolescent kids. Are we not? We’re seeing some of these potential challenges manifest in our adolescent population, and so, we can do something about it. 

Dr. Kara Fitzgerald: Well…

Dr. Leslie Stone: Let me emphasis too that that group dynamic is a creation of community.

Dr. Kara Fitzgerald: Yes.

Dr. Leslie Stone: …in itself.

Dr. Kara Fitzgerald: That’s right. 

Without question, especially during that scary time of being pregnant with all of the questions, it’s just heavenly to have humans and then of course, after delivery. Well then let’s talk about where you left us Emily, just talking about adolescents, and the stress that they’re under and probably having some epigenetic changes. Pushing that from the birth phenotypes. Let’s talk about what you found are the F1 and trans-generational effects of the phenotypes that you’ve just put forth. 

Dr. Leslie Stone: I just have something that’s floating around in my head, we were talking about the women. I’m kind of backing into this, I think a little bit, but that is one of the other profound effects that we’re finding is that we are talking about the women, but we need to be talking about men.

Dr. Kara Fitzgerald: Yeah, we do. Yes.

Dr. Leslie Stone: Yeah, and so, because for these nutrients, these microbiomes, the aging population, these stressors do play a role. And the one for male fertility, but also for these birth phenotypes. The maternity drive, the frequencies, incidents, of maternal adverse outcomes and those neonatal adverse outcomes. So one of them that I want to point out, it was just kind of mind boggling, we were talking about epigenetic mechanisms, and one is that if a male happens to have one of these high stress scores, that they have a micro RNA change in their sperm.

Dr. Leslie Stone: That translates into a stressed phenotype in the neonate. 

Dr. Kara Fitzgerald: Thank you for bringing that to our attention. This is not gratuitous, let’s bring the guys in here. This is now that we’re swimming firmly in the -omics pond, and the systems-biology… Men are as significant players. Of course women are carrying the babies, and that’s why you’re giving a certain kind of attention to them, but yeah, thanks. Thank you.

Dr. Leslie Stone: So then coming back to that question of, what are the trans-generational effects of these phenotypes, so that’s where we kind of left off.  Yeah, and that is, I think that you, you talked about preterm birth first, because it’s so profound.

Emily Rydbom: Well, I think what’s interesting about… So if we just choose one phenotype, and in this case, we’re going to focus on preterm birth, and we talk about this generational impact of just that outcome. If a mother is carrying a daughter in utero, and she delivers that daughter preterm, then her daughter is more likely to deliver her granddaughter preterm, and then her granddaughter is going to deliver her great-granddaughter preterm, and the cycle continues. Now, what breaks that cycle? One full term birth. 

That’s it. That restarts their new health story. So I think even just in the simplest term, preterm birth begets, so to speak, preterm birth. And if you’re talking about preterm birth as an increased risk of morality and morbidity, there’s not a greater phenotype than preterm birth. 

Dr. Kara Fitzgerald: From what? From just anything? Or what specifically?

Emily Rydbom: Yes. So perinatal mortality specifically, particularly in the infant, higher risks of complications, developmental issues, that whole conversation of the NICU complications that come to at that term.

Dr. Leslie Stone: At that perinatal time period.

Emily Rydbom: And then extending further into their life, too. Increased risk of asthma, wheezing, eczema, allergies, autism spectrum disorder, and the so on and so forth, because it’s not just preterm birth. Those babies are often also born small for gestational age, and so then they have a double impact of these phenotypes, and if we’re talking about the highest cortile risk of trans-generational health, and these shortened long-term outcomes, it is small for gestational age that rises to the top of these chronic disease risks. 

So then you have a double whammy, and all of that sounds so dire, but I think what has been really amazing about what we have done and what we have tracked over the course of these last ten years, is that these interventions dramatically decrease those rates to the point where some of them don’t even present, Kara.

I mean, and so, we always kind of look at each other and go “What is it exactly that we’re doing?”, and what we are doing is we are, the simplest way, we are meeting each individual epigenetically, where are they at, with their vulnerabilities with their n of 1 story. And we do that, and then we just repeat that process.

Dr. Kara Fitzgerald: Right, right. But your interventions are straight forward. This is incredibly complex, don’t let me move into the underlying mechanisms, but administering your interventions, while very precise, are relatively straight forward. So what might be something that you might do when they’re at risk for preterm delivery. 

Emily Rydbom: Well, so this is actually our most recent favorite developmental programming of health and disease science, and it came out of a Kansas study, it’s called a Kudo Study, and all that was done, was 700 milligrams of DHA was given in the second and third trimester to the mother-baby diet, and it was given over the course of two trimesters. It markedly decreased the rates of preterm birth to the tune of, if they were to extrapolate that rate decrease over how many preterm births occur in this country today, it would decrease the GDP by six billion dollars of health care associated costs with preterm birth.

Just by applying appropriate omega-3 fatty acid supplementation in the second and third trimester, so I giggle a little bit when we talk about how single interventions may not be as powerful as a whole, but that does not take away from the power of these single interventions too. And when you put it all together, then that’s where we get blown out of the water.

So just for preterm, that’s one way that we can decrease preterm birth. We can improve vascular function, we can make sure that we are addressing and decreasing risks of pregnancy induced hypertension with appropriate arginine, and citrulline, appropriate proteins, nitric oxide, and what we do for women, is that we translate it into things they know like kale, tomatoes, beets, watermelon, and walnuts. You can’t have access to those, then let’s find the one food you do have access to and let’s start with that one. 

And so, we break it down to the point where they literally are walking through the door and they have one single food plan with their main focus nutrients in these foods, and they can take that to the grocery store, and say, “This is my next best decision”.

Dr. Leslie Stone: The other important piece of this is that, how long does it take? I always like to include, Emily particularly likes to include how long does it take to make a change? We’d be giving a nod to that rapid epigenetic modification capabilities. There’s a really interesting study where they looked at good fats versus bad fats, and they looked at the different enzyme activities, transcription activities associated with the different of these enzymes and transcription particularly, that had to do with fat metabolism, they found that, depending on which diet you gave them, that fat, that it took about six hours to modify that gene expression.

Dr. Kara Fitzgerald: That’s really extraordinary. Yes, it’s a continuum. I think that’s what you’re getting at, so the resilience of those epigenetic changes, like the Dutch hunger winter study that we originally started to talk about, we see trans-generationally. There’s no doubt about it, it can have negative impact, but then Emily pointed out that you can absolutely shut down premature delivery with very simple interventions, and shut it down generationally in a relatively straight forward way, and now Leslie you’re saying that you can turn things around in as little as six-hours time. It’s just pretty extraordinary, isn’t it?

Dr. Leslie Stone: Our bodies are meant to be resilient. We just have to figure out the code, that’s all.

Dr. Kara Fitzgerald: Yes. It’s getting in there with the intervention at a very precise moment in time, and that’s what you’re doing. So let’s talk about that in terms of the four trimesters of pregnancy and how they might differ in their emphasis. I’ve got a handful of questions, additional questions for you, and we’re sort of heading on the home stretch of our time. So with that in mind, just talk to me about those four trimester pregnancy differences.

Dr. Leslie Stone: We’ll start with preconception. I think the best example is one that many people are aware of. There’s this impressive study out there that says if a mother is lacking in B-vitamin nutriture, single carbon metabolism sub-straights, in the three months before she conceives, and the one month after she has conceived, and she has two particular gene variants: the MTHFR and the COMT, and another factor. Another variable. Her baby happens to have another one of those single carbon metabolism gene variants called CBS, then that baby, simply for lack of B-vitamin nutriture, has a 720% increased risk of autism compared to the same genetic profiling with adequate B-vitamin nutriture in the preconception and one month post conception time period.

So, there is this set up. This genetic set up. This epigenetic set up that is profound in that preconception time period, and into the first month of the first trimester. Then, the next thing that happens in that first trimester, is there’s this profound methylation. Single carbon metabolism step that’s happening in DNA methylation, it’s rapid. It’s fast. And there’s a big requirement for those factors, otherwise, because during that time period, that we’re deciding which cells are going to be what. 

Such that, by the time we hit about thirteen weeks or so, they have pretty much decided what’s going to be what, so in the next trimester, we have building and increasing complexities and interconnectivities within those organ systems. So that has a different set of nutriture that’s associated with it, and also that DNA, that DNA methylation drops dramatically during that time. 

Dr. Kara Fitzgerald: So after their stem cells have been given their marching orders, so they know their fate, so they’ve moved out of that, then you start building. So that would be how your requirement for protein I’m assuming, and that…

Dr. Leslie Stone: Yes. And then, as we head on into that last trimester, the two target organs I think of most profoundly are the heart, but also the brain. It’s trying to make all of those connections at that time, is trying to add a lot of fat. And so, we’re talking about maximizing that healthy fat piece of it. The EPA and DHA, and then in the postpartum time period, we’re trying to decide that fourth trimester as we call it, we’re trying to make that transition successful through breast feeding, through adequate nutriture. Because those babies continue to have these continuing needs. They still need adequate single carbon metabolism support, they’re still potentially at risk for these nutrient insufficiencies, we need to meet those through meeting the mother’s needs, or if the mother is unable to do that breastfeeding piece of it, then we have to be able to support it in other ways.

And, of course, we all know that there’s varying stressors, so let’s go back to the lifestyle piece of this and support piece of this. It turns out that during that first trimester, that organogenesis, yes it’s susceptible to stress, but it’s particularly the differentiation piece of it, the growing of the cells in the second trimester that is particularly susceptible to perceived stress. And it’s at that time that we have the greatest ability to have an intervention that is successful. 

It is interesting to me that in the third trimester, stress perception drops, and that probably has to do with all sorts of cortisol, feed-forward cortisol effects. But whatever the case is, the setup for a mother who is stressed in that second trimester is more likely to deliver preterm. The one who was stressed in the third trimester doesn’t have a huge increase in that preterm birth rate. So it’s interesting that there are time periods that have to be addressed sequentially and intentionally.

Dr. Kara Fitzgerald: Wow. I really look forward to your book. I look forward to just understanding this journey in more granular detail, and I look forward to learning more from you on this, because it’s just absolutely extraordinary. And you know, again, folks, if you want to listen to that Randy Jirtle podcast, he and Waterland have the most cited paper in the history of science, and that paper was on what Leslie and Emily are doing right now. He was in an animal model, but he put the influence of nutrition in phenotype expression… During early embryogenesis is when they yielded the most influence in these animal models and the phenotypic expression in the adult offspring. He put that whole journey on the map, and it’s called the Agouti Mice studies, and I would encourage you to look it up or take a listen to the podcast where we talk about it. 

Dr. Leslie Stone: The translator for that information is that, we went, “Oh, see? We do have an effect. A nutritional effect.” All things that we seem to know, that profound difference between addition of these methylating nutrients to a control diet on a mouse would make the difference between an obese, a diabetic, early balding, and one that lived a happy, slim, dark haired life. He’s kind of a major hero to us, and there’s a great book, that I think that if people were really truly interested in this, and he’s an editor along with a man named Tyson. Randy Jirtle and Frederick Tyson Environmental Epigenomics in Health and Disease.

Dr. Kara Fitzgerald: Yeah, because they went on and showed this different phenotypic expression. Obese. Cardiovascular disease. Cardio-metabolic, et cetera outcome, or healthy with not just introducing methyl donors like folate, and so forth, but negative outcomes with BPA exposure or beneficial outcomes with genistein. Yeah.

Dr. Leslie Stone: Then if you’re going to intervene with that DNA methylation marks, and that also so… How do we get a trans-generational effect. It was by shutting down certain parts of the transcription of the DNA.

Dr. Kara Fitzgerald: Yes. That’s right.

Dr. Leslie Stone: Over decades, over generations, could reverse, but you could also reverse it with a diet. 

Dr. Kara Fitzgerald: Yes, that’s right. It blew the lid off, they just blew the minds of many scientists when they demonstrated that. 

Well talk to me, just, in the home stretch here. Well we know you’re headed with the book, but just some big picture stuff around this work that really excites you. Just give us some words of wisdom from this extraordinary journey you’ve been on, or something that inspires or has been influencing you lately. I’m just going to open it up. 

Emily Rydbom: I’m going to start out with some dire news first, but then my excitement that is associated with it. And also, our excitement is, I think when we look at global health rates, and we look at global rates of these phenotypes, I have to sadly report that, besides Malawi, in our world, Mississippi Medicaid has the highest rate of preterm birth in the world. 

Dr. Kara Fitzgerald: Wow.

Emily Rydbom: And then Mississippi as a state is within top Third World countries of preterm birth, and the highest rate in the United States, and so, I think more than anything, what excites us, and some work that we’re starting to do, and we can’t divulge wholly, but it definitely lives in this world is that we’re looking to apply this model in 100% Medicaid vulnerable populations. And so, if there’s something that excites us, what excites us is that what we have done may be able to translate into health and resilience within populations that have some of the highest rates of these social determinants of health. 

And so, for us, that’s unbelievably exciting and is something that has been, I think, a dream of ours for a very, very long time. And, because it’s a headline we don’t really want to be known for, particularly when we’re otherwise a plentiful, rich nation, and yet we still are not doing a good job. That’s something that we’re very excited about, and then, we really didn’t get to get into the autism…

Dr. Kara Fitzgerald: Oh yeah, of course.

Emily Rydbom: A little bit, but I think it’s important to say that there was a study that was published in March, and it had to do with pesticide exposure and increased risk of autism in a baby, and that for those mothers who lived as close as two kilometers to any field that’s being sprayed with herbicides, pesticides, fungicides, that it increases autism risk in that child by almost thirty percent, and if they continue to live in that space, that child’s increased rate increases to fifty percent.

That all sounds horrible, except, what do we know? We know that this one carbon metabolism sits at the center of our ability to detox, so what does that mean? That’s an opportunity for us to target those detoxification pathways, target that one single metabolism, and improve its efficacy during this time period, rather than say “Sorry, you’re going to have to move.”. Which is not going to be an option. We educate around what you can do to provide that resilience. We educate around, if you can’t buy organic food, how do you wash that food to decrease pesticide residue exposure? What are the dirty dozen clean fifteen? What sulfur rich foods can we include every day? Can we make sure that you’re pooping every day? Can we make just simple things, going back to “How can we take care of this basic physiology even knowing that the risks of exposures are increasing daily?”

Dr. Kara Fitzgerald: Yeah. Amen to that, and again Jirtle and Waterland actually demonstrated just what you’re saying Emily. But more importantly, really, is that you have shown this in the five thousand babies that you’ve delivered Leslie, and the work that you’ve done there. You have shown success with these interventions.

Dr. Leslie Stone: We’ve had an opportunity to, now since our initial work was published in 2014, but it represented 2011-2012, we have now been able to follow and published our longitudinal kid outcomes, right? And we just practically never have a kid with autism. One, at this point.

Dr. Kara Fitzgerald: One in about five hundred?

Dr. Leslie Stone: Yeah. And we have a few others who have attention deficit, but it’s just a fluke. We have a less than 1% rate of atopy, asthma. We have, up until January, we had zero preterm births, and now as of January we have one preterm birth.

That’s it.

Dr. Kara Fitzgerald: So you can count on two hands. Complications seen elsewhere, as the dominant paradigm distant in your practice, well anything I can pop up on our show notes just to talk more about this, everybody will want to, to read about it. I want to say that if you need donations, if you need support, certainly I’m feeling like I want to be behind you and really help facilitate the work that you’re doing, and I’m sure that if I’m feeling that way, that there are people listening to this that also feel that way, so, as it unfolds, if you need us, we’re a community who’ve got your back and we want to participate.

Emily Rydbom: That’s an amazing, and I’ll back at you. As of last week, we have official 501(C)-3 status in the state of Oregon for our non-profit arm called Grow Baby Life project.

Dr. Kara Fitzgerald: Ah, beautiful.

Emily Rydbom: And so, that website is being developed, we’ll come up probably in the next couple months, so yes. I think what is so impressive to me, Kara, about you and your work and the world that we all live in, is that cheerleading that does happen for all of our colleagues. We are all just hoping and just cheering and wishing the best on each other, and so-

Dr. Leslie Stone: Truly engaged and healing the world.

Dr. Kara Fitzgerald: Yeah.

Emily Rydbom: If we get to walk amongst all of you, man, we are lucky people.

Dr. Leslie Stone: Good company.

Dr. Kara Fitzgerald: It’s so extraordinary, all right, well listen ladies it was just a really nice time being able to talk to you today, and I’m just so thrilled to spend some time learning in greater detail about the important work you’re doing out there, and everybody will want to know more. Stay tuned folks, we’ll continue to publish Grow Baby info on our site and send it out in our newsletters and so forth, and of course you’ll have our show notes, and you can hop over to their site as well. 

Thank you so much Emily and Leslie for hopping on New Frontiers with me today.

Dr. Leslie Stone: Thank you for your work.

Emily Rydbom: Thank you, yes absolutely.

Dr. Kara Fitzgerald:   And that wraps up another amazing conversation with a great mind in functional medicine. I am so glad that you could join me. None of this would be possible, through the years, without our generous, wonderful sponsors, including Integrative Therapeutics, Metagenics, and Biotics. These are companies that I trust, and I use with my patients, every single day. Visit them at IntegativePro.comBioticsResearch.com, and Metagenics.com. Please tell them that I sent you and thank them for making New Frontiers in Functional Medicine possible. 

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