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

 One of the first things on an embryo's to-do list is to make a placenta, but to do this, it will need to work well with the decidual cells occupying the future Placenta construction site, otherwise known as the decidua or uterine lining that's beefed up for pregnancy.

There are likely many contributors to this process, but how this negotiation goes down between a specific set of immune cells called uterine natural killer cells, or uNK cells and the fetal cells from the embryo that set up the bridge between the mother's body and the placenta called the trophoblast cells, or EVTs is the subject of today's episode.

Also: why great obstetrical syndromes (preeclampsia, IUGR, stillbirth) is more of an issue for humans than other mammals.

Although your OB usually doesn’t want to see you in the early weeks of pregnancy—there’s a lot going on that is of critical importance to the ease or complications of a pregnancy—specifically , the introduction of fetus to your uterine lining, and the subsequent merging, if implantation happens. 

The weeks that follow are equally consequential. Exactly how those cells of your uterine lining negotiate the migration of trophoblast cells, fetal cells that are building the placenta can be the difference between preeclampsia, premature birth intra uterine growth restriction and a normal pregnancy. One main negotiator of this migration is a specific type of immune cell, uNK cells. Today we talk to a world expert on how certain elements of the immune cell function in early pregnancy.  

Dr. Ashley Moffett's 2022 paper in Nature Review Immunology: https://pmc.ncbi.nlm.nih.gov/articles/PMC9527719/#Sec1

We are going to talk about the menstrual cycle, aka the result of the conversation between your brain, pituitary and ovaries that’s going on each months to create the conditions for you to build a human. 

How does your body accomplish this amazing feat? 

You likely experience your menstrual cycle, and your period in particular, as an inconvenience, but evolution put a lot of hard work into this process and it turns out to be pretty nifty. 

We’ll also talk about the why today. Most mammals don’t have a menstrual cycle. Why do we think humans do? 

And how are the ways we have figured out to control that cycle operating in this complicated chemical conversation going on in your body?

 Are the movers and shakers of the menstrual cycle, the specialized cells that make all these changes happen each month, are they good for anything else? 

We’ll walk through these topics today.

Questions or comments? write to [email protected], or find me on instagram @makingsenseofpregnancy

Current statistics suggest that postpartum depression is one of the most common complications of pregnancy in the US, estimated at between 1 in 10 and 1 and 5 women--and this estimate is mostly based on the response to survey responses. 

 The Edinburgh Postnatal Depression Scale (EPDS) is the most widely used screening tool for postpartum depression (PPD), recommended by ACOG, USPSTF, and PSI for universal screening at the 1-12 week postpartum visit, and is an imperfect tool to catch all cases.

Contrast that to childbirth related PTSD--which is believed to be nearly as common, and for which no standardized screening tool exists. 

It's important to distinguish one from the other because the treatment is different for PPD and CB-PTSD.

Dr. Dekel shares why the distinction is important and ways we might use to catch CB-PTSD early.

 The very first construction project in pregnancy is the placenta. It's critical to the embryo's development, and problems with the placenta can have significant consequences for the baby. Since doctors have been able to identify fetal growth restriction in the course of pregnancy--which started in about the 1970s-- the medical response has been to prescribe bedrest and or early delivery.

In the second half of my conversation with Dr. Helen Jones, we talk about how this response to fetal growth restriction may give way to new gene therapy that can fix the placenta during pregnancy. 

 If you're listening to this episode on placental gene therapy, you may wanna sit down. 

Today's guest walks us through a gene therapy that (a) doesn't change the chromosomal DNA of the mother or the fetus; that (b) can reverse (you heard that right)--REVERSE placental insufficiency after it has taken hold, and as if that weren't enough, (c) has successfully restored fetal weight in growth, restricted Guinea pigs, passed safety checks in macaques and maybe in clinics as soon as five years from now.

To look at Dr. Helen Jones' work, see: https://physiology.med.ufl.edu/profile/jones-helen/

The paper we use as a scaffold for our conversation today: Placental Gene Therapy in Nonhuman primates: a pilot study of maternal, placental and fetal response to non-viral, polymeric nanoparticle delivery of IGF1: https://academic.oup.com/molehr/article/30/11/gaae038/7876288?login=false 

 Many headlines exclaim the wonders of AI and medical research. What better place to leverage the advantages of AI than in research about pregnancy that positively impacts everyone's health, both in the present and the future? And by that I mean the mother and the baby during the pregnancy and the baby's health trajectory into the future--and maybe also the mothers as well. 

Today's guests are an uncommon duo, a computer scientist, and an OB who are using big data algorithms and clinical experience to uncover the biological basis for some of the biggest issues in pregnancy. In particular, they're interested in the root causes of vascular issues that may develop into preeclampsia and or preterm birth.

Today we talk about a new way for researchers to approach some of the biggest puzzles in pregnancy. 

 Never before in the history of humanity have we been able to examine a pregnancy in process and predict the risk of conditions before clinical symptoms have developed. Even 10 years ago, if you told an OB that you could reliably predict which pregnant women were most likely to encounter preterm birth in their first pregnancy, you'd likely be written off as a kook. The power to predict complications in pregnancy, premature birth, postpartum depression, and other postpartum states is a marker of phenomenal progress.

For the second part of the end of the season recap, let's walk through some more of the amazing research and findings we talked about in the first season of the show that will change how we think about and manage pregnancy going forward.

 Looking through some of the research I highlighted on the podcast this year gives me a real sense of hope about the future of pregnancy, and I hope it does for you too. 

There's good news and bad news. Let's get the bad news outta the way first. It's true that women's health has gotten the short end of the stick in terms of federal funding and research interest for far too long, and research on pregnant women has gotten an even shorter version of that stick. It's still considered niche research in many quarters, despite the fact that. Every existing person owes their existence to a pregnancy, and what happened in that pregnancy likely affected important aspects of their lifelong health. That's the bad news. 

The good news is research on topics around fertility, pregnancy, birth, and postpartum have dramatically increased over the last 30 years. So for today's end of the year episode, I'm gonna take a walk through a theoretical pregnancy that's happening today with a tourist's eye for some of the amazing research we covered on the show this year. Of course, I can't distill 50 conversations into a half an hour, but let's walk through early pregnancy and see how this research may reshape how we think about and manage the first trimester.  

I am both hopeful and moved, AND filled with disbelief after my conversation with today's guest. 

He is an OB who has done an inordinate amount of work to make birth safer first for Californians, then for women across the country. His work, which you'll hear about and be able to use in your own pregnancy, is inspiring. 

What I can't get my head around is the state of maternity care he set out to change in 2006, some of which remains unchanged. 
Does it make sense that you don't really know the quality of care you'll get at your birth because hospitals didn't keep track of their health outcomes in a useable way? 
Does it make sense that C section rates vary widely between hospitals? 

No dear listener, it does not. 

We talk about the importance of data being collected and quickly disseminated so that hospitals actually know the quality of their maternal care and can compare their care with the care neighboring, and what should be competing hospitals, do, and you, too, as the consumer, can get a better handle on what you are walking into when you pick a hospital in which to give birth.