Making Sense of Pregnancy: What Experts Want you To Know About Your Body

This week's episode feels, in some ways, like an admission that The easter bunny isn't real, and spoiler, neither is santa...we focus on research that considers ways to predict spontaneous preterm birth. Preterm birth (which is anything before 37 weeks) comes calling for many different reasons, which is one of the challenges of studying it...but today's guest talks about some real breakthroughs she and her colleagues found in terms of using information we've had for decades to better predict preterm birth for a specific set of mothers, and what techniques we are currently using that may not have the data to support their use.

A link to Dr. Herrera's paper: Revisiting the placental clock: Early corticotrophin-releasing hormone rise in recurrent preterm birth

 https://pmc.ncbi.nlm.nih.gov/articles/PMC8445461/

The star of this episode is the trophoblast cell. It goes for broke during implantation, fully embeding into the uterine lining and laying down the early building blocks of the placenta. This action is given an appropriately dramatic name:  trophoblast invasion. I’ll share some of the sci fi details of how a ball of cells, only half related to you, burrows into your body, creates a new organ to change the way your body metabolizes food and syphons off your nutrients and oxygen to grow. 

Keep in mind that there are a ton of chemical reactions going on to make this happen and it is in fact happening while you are in line at starbucks, working at your desk or out for a run….

Today’s episode breaks down this critical process in some detail for three reasons: (1) its not at all uncommon for pregnant women to hold themselves responsible for things in a pregnancy that go wrong.  Settle in for this episode and listen to the boatload of complicated things going on in your body that you couldn’t possibly control even if you wanted to; and maybe loosen your grip on this idea that you are responsible, (b) This is one important inflection point–errors in this phase can have significant consequences for the rest of pregnancy, and potentially for the health trajectory of both the mother’s health and the baby's health going forward, and (c ) If you know some of these details you can appreciate  some of the amazing work being done to try to address these errors.

Perinatal mood disorders represent one of the most common complications of pregnancy--1 in 5 women will experience this during or after their pregnancy; a sizeable fraction of these women experienced some kind of mood disorder prior to pregnancy--but currently it's hard to predict how pregnancy will mix with this history. My guest today shares with us what the future of pregnancy could look like; using advanced scanning technology, we may be able offer a much more accurate estimate of the chances of experiencing depression in pregnancy based on a look at a mom's brain structure​.

You can find Towards Personalized Clinical Interventions for Perinatal Depression: Leveraging Precision Functional Mapping here: https://www.science.org/doi/10.1126/sciadv.adt8104

You can find Dr. Sheila Shanmugan's (MD, PhD) work here, at the Perelman School of Medicine, University of Pennsylvania: https://www.med.upenn.edu/apps/faculty/index.php/g275/p8364165 

Charles (Chuck) Lynch et al 2024 Nature paper on mapping depression: https://pmc.ncbi.nlm.nih.gov/articles/PMC11410656/#Abs1

Dr. Laura Pritschet's episode on the show: https://podcasts.apple.com/us/podcast/its-not-mommy-brain-how-hormones-during-pregnancy-prepare/id1779600854?i=1000679984230

 Pregnant women live two lives simultaneously. They're going about their days, driving to work, or sitting down for coffee with a friend, essentially  living the lives they were in before they got pregnant. But now, at the same time, they could be doing it while also growing another human, laying down a brain stem, or working on a fetal heart. 

All these developmental things are going on, and you don't have direct control over them. In my pregnancies, I felt the weight of responsibility for all the things going on in my body. Even though I understood  that I couldn't directly control them. I don't think I spent enough time marveling at all the amazing things my body was doing.

So today I want to look at a few of those  things, focusing on some of the details of implantation, the unbelievable steps involved when an egg burrows into the uterine lining. I'm going to share details about some embryo hacks to make it into the mother's body.  Please enjoy this solo episode.

What happens in the womb doesn't stay in the womb--so said David Barker in the 1990s, a British epidemiologist, ​Barker found associations between birth weight and the likelihood of developing cardiovascular disease later in life.​  He argued that the uterine environment can have long term effects on future health.  Much work has been done to map out exactly how ​fetal experience during pregnancy translates to someone's health trajectory.​ Today's guest is using omics data and placental samples to more clearly trace out how exposures in pregnancy can impact fetal development and long term health .  

To see some of Dr. Paquette's work: https://www.seattlechildrens.org/directory/alison-paquette/

Intergenerational Transmission of Environmental Exposures, Michael Skinner: https://www.youtube.com/watch?v=f1Pf5S8Nbfk

Every popular depiction of a woman in labor that you've ever seen on TV or in movies or experienced yourself contains one real truth: the start of labor is a surprise. It's a surprise because despite the many things we do know about labor, we don't know how or why it's initiated. What series of things have to happen to get labor to turn on, and why-- in one in ten births in the US-- does it turn on too early? This is the topic My guest, Dr. Todd Rosen, talks about today. He and his collaborator Bing bing Wong have developed a compelling theory about the conversation between the placenta and the fetus that may explain what the triggers are. 

Dr. Rosen's paper on the placental clock: https://rep.bioscientifica.com/view/journals/rep/168/3/REP-24-0053.xml

You can find more of Dr. Rosen's work here: https://pubmed.ncbi.nlm.nih.gov/?term=Todd+Rosen&sort=date

Dr. Rosen references the episode with Dr. Hoffman, focused on how aspirin impacts preterm birth: https://podcasts.apple.com/us/podcast/the-surprising-role-of-aspirin-in-fighting-preterm/id1779600854?i=1000684963648

Each baby is born with a pregnancy diary they've kept while they've lived in their mother's body, otherwise known as the placenta. In the US, only about 20% of placentas are dissected after birth and carefully examined under a microscope, usually to better understand what went wrong in cases of  intrauterine growth restriction or stillbirth; and for the other 80%, (that's more than 3 million births a year) this diary, that contains information about lifetime risk for diseases for the mother, like diabetes and hypertension, and may also include information about likely also holds information about lifetime risks for the baby's future health, for this other 80%, the information is tossed out.

One reason for this desperately poor use of this resource is cost: it costs too much. Today I'm speaking with a researcher and placental pathologist who is part of an amazing team marrying AI to placental pathology to dramatically reduce this cost and make this information more easily accessible and widely available.

Here is Dr. Goldstein's faculty page where you can find publications and bio information: https://www.feinberg.northwestern.edu/faculty-profiles/az/profile.html?xid=41408

To find more about PlacentaVision: http://www.placentavision.com/

To access the show we referenced in this episode with Dr. Mana Parast, 

click here and here

 Monitoring contractions in labor hasn't changed in 50 years--the most often used tool, the tocodynamometer, uses an indirect, one dimensional view of uterine activity in labor. 

Dr. Wang talks about applying the tech used in cardiology to the uterus, to create a three dimensional way to non invasively measure electricity as it travels through the smooth muscle of the uterus, creating contractions.  His lab is working on the tech that would allow us to distinguish, and potentially arrest preterm labor, to potentially jump start arrested labor, and to create a uterine measure of labor stages (which could be used in conjunction with cervical checks). 

 Understanding how the uterus works and the wearable technology that this work promises gives a sense of how complicated the uterus is when contractions feel fierce or labor stalls.  It may also have applications that ease period cramps and monitor and potentially "turn off" endometriosis. 

Wang Lab: https://reproductivesciences.wustl.edu/laboratories/wang-lab/

Dr. Wang's publications: https://www.ncbi.nlm.nih.gov/sites/myncbi/1Tux87w_RnEkl/bibliography/47687944/public/?sort=date&direction=ascending

You may not have given much thought to the lining of your uterus, aka your endometrium; but it is a super important workhorse when it comes to pregnancy, and one that, it turns out, has a voice. The old story used to be that the endometrium is this passive, patient group of cells waiting to give any embryo it glimpsed a warm, safe harbor to grow. Today's guest shares the updated story: the endometrium as selective screener, interviewing the embryo--by assessing its chemical signals-- accepting and investing in the embryos it thinks are viable, and rejecting the rest.

Nick Macklon's published work can be found here: https://pubmed.ncbi.nlm.nih.gov/?term=nick+macklon&sort=date 

Uterine Selection of Human Embryos at Implantation: https://pmc.ncbi.nlm.nih.gov/articles/PMC3915549/

Dr. Macklon's work at the London Women's Clinic, Kind IVF

On average in the US 1 in 10 babies is born prematurely and, in many cases, the cause is unknown; although there could be many contributing factors, nearly 40% of pregnant people who deliver before 37 weeks exhibit chronic placental inflammation, which happens when the mother's immune system attacks the placenta. 

Today's guest is trying to decipher the conversation between the immune system and a pregnancy.  If we understood this conversation, we could look for ways to predict and potentially prevent preterm birth, and in the process we are learning more about how spontaneous term labor happens (which is, somewhat shockingly, also a mystery).

Center for Reproductive Health: Gomez-Lopez Lab

article that launches this conversation:
Deciphering Maternal-Fetal Crosstalk in the Human Placenta during parturition using single cell RNA sequencing