Joey Wahler (Host): It can affect both mother and baby. So, we're discussing chorioamnioitis, also known as chorio. Our guest is Dr. Viral Jain. He's an Assistant Professor in the Division of Neonatology at the University of Alabama at Birmingham.

This is the Children's of Alabama PedsCast. Thanks for joining us. I am Joey Wahler. Hi there, Dr. Jain. Welcome.

Viral Jain, MD: Thank you so much for inviting me today.

Host: Oh, great to have you aboard. So first in a nutshell, for those unfamiliar, what is chorio and how is it typically diagnosed in a clinical setting?

Viral Jain, MD: So, chorioamnioitis is basically inflammation of the placenta or the membranes, which surrounds the baby when the baby is still in the womb. So, it's very hard to look inside the womb when the mother is pregnant. So, it's usually defined by using what we call clinical criteria. So, the markers of inflammation such as temperature, baby's heart rate, mother's heart rate, which could signal something inflammation is happening inside the mother. But a more definitive way of diagnosis is, once the baby is delivered, we can actually go look at the placenta and actually look for inflammation, and that's what we call histological chorio diagnosis.

Host: Now, before we go any further, you've actually done a ton of research on chorio and how it affects preterm infants. I'm wondering what sparked your interest in this topic in the first place?

Viral Jain, MD: Well, chorioamnionitis or chorio is like the number one reason why babies are born preterm. So, the earlier the baby is born, so let's say 22, 23 weeks, about 80-90% of the babies are born due to chorioamnionitis. So, it's a huge reason of why neonatology exists as such. So, I'm just trying to kill my own field to better understand how we can prevent chorio so we can have less babies being born premature and, ultimately, healthier babies.

Host: Wow. Interesting indeed. So, what are the most common causes of chorio? And how can they be prevented during pregnancy?

Viral Jain, MD: So, you have to think chorio, which is inflammation of the placenta, like fever. There are many causes, which ultimately leads to fever or chorio. Infection is one of the causes, but only one-third of them actually is due to infection leading to chorioamnionitis. There are many other causes such as environmental, chemicals, smoking, bleeding, and it's still an active research field to figure out why is it happening.

Host: Anything that pregnant moms can do to help guard against it?

Viral Jain, MD: So, that is a very active area of research, which I'm also involved in. The thing is we have such poor understanding of how it happens, how it increases in mothers, how is it going? It's very hard to say what the mothers can do to prevent it. And it's very short-acting. Once a chorio starts, the baby delivers within three days. So, it's very hard to catch it earlier too.

So, we are just trying to figure out if we can do something such as environmental chemicals, which are triggering chorio, can these be prevented during pregnancy? So, a lot of active area of research going on there.

Host: Wow. So, it sounds like professionals need to act very quickly to say the least once they discover this is present. How do they discover that?

Viral Jain, MD: So, it's due to the clinical signs, which I initially discussed. So if the mother has fevers, if the baby's heart rate is too high, or the baby's showing signs of stress when they are monitoring the baby, there are signs that the baby is going through some inflammation process, and that's probably most likely due to chorio. And to save the life of the mother and the baby if it progresses too much, the baby needs to be delivered before there's a lot more damage to the baby.

Host: Understood. So, how does chorio affect the outcomes eventually for both mother and newborn?

Viral Jain, MD: So, speaking mostly for the babies, if the chorio is due to infection, the mother's going to be sick from that infection and the baby's going to be affected too. But primarily, the chorio which happens is mostly a silent indicator. It's only one-third of the babies are actually diagnosed with clinical chorio.

And when you go look back at the placenta under a microscope, there's only one-third of ones who are detected. There's so many which are silent, which do not show any overt clinical signs, but there is damage from that inflammation. And their damage could lead to the most primary being just born preterm. It's a body's reaction when there's inflammation that would just deliver the baby preterm. And all the complications that come with the preterm baby are due to those chorio. And in addition, you have the inflammation causing direct damage itself to the developing organs of the baby.

Host: Okay. So, we mentioned your research. We're going to delve into this a bit now. Some of your studies note that risk for neurodevelopmental impairments attributed to this chorio in premature infants remains controversial, if you will. So, why is that?

Viral Jain, MD: So, that's mostly due to methodological issues like how the chorio was defined. As I said, only one-third shows clinical signs of chorio. And even those, the one-third which shows clinical signs of chorio, it's very hard to see what is true chorio, or just what we call false negative, a false alarm, because we do not have really good understanding of why it happens.

And when you use that definition, which itself is not good to define chorio and you use markers to measure developmental outcome, which are also not really good, you lead into this controversy to a certain damage due to chorio. So, my work has been more to define chorio using a proper definition of chorio and more proper definitions of neurodevelopmental, which actually parents care about to a certain what the damage from chorio is to the developing brain.

Host: Gotcha. Now, one of your studies examines whether extremely preterm infants exposed to chorio or funisitis as well are at a higher risk of death or cerebral palsy compared to those without these exposure. So, what is funisitis and what did you learn from that study?

Viral Jain, MD: So, as I said, chorio starts in a small, what you call mild chorio and progresses rapidly in few hours to days to what they were call moderate to severe. And that just tells us the amount of inflammation happening in the placenta. When that inflammation is too severe, that is not confined by the boundaries of the placenta and enters and affects the umbilical cord of the baby itself, that's what we call funisitis. So, it's basically inflammation of the umbilical cord due to the inflammation of the placenta, and it just suggested just a very severe form of chorio. So, what we try to make sure there's no further controversy on whether it affects development or not. We just chose the most severe form of chorio babies to clearly show that it affects cerebral palsy development.

So, that's one of the first times we have clearly shown, and there's always this controversy. It's because the baby's born preterm that we have cerebral palsy, not because baby had chorio, so that we try to divide it and see what we call causal effect to see how much of it is due to being born preterm, and how much is due to direct effect of having funisitis or chorioamnionitis. And it was about 50/50. So, half of your risk of cerebral palsy was from being born preterm due to chorio. And half was the direct injury coming from the inflammation to the developing brain.

Host: Now, another of your studies concludes that histological chorio increases the risk of BPD. So first, tell us what histological chorio and BPD are, what the latter stands for, and what can you tell us about that scenario?

Viral Jain, MD: As I said, chorio is mostly silent and, even clinical chorio would be diagnosed with clinical signs, it's not very accurate. So when you look at placenta and see inflammation signs, and when you trace those babies born who had those placenta, how they do, the development outcomes, they're more to give us a better idea of what's happening. So, we looked at the lung function. So, brain's important. And for us, the acute lung is the second most important organ. Or if you ask someone else, that is their most important organ for them.

So in the lung, what we found is those babies who are born due to chorio, they have chronic lung damage. So, even if there is an initial insult at birth, it creates an immune cell dysfunction in the lung that there is continuous damage happening. And these babies continues to be on the ventilator for longer, continues to get oxygen for longer. And these babies end up developing what we call BPD or bronchopulmonary dysplasia or neonatal chronic lung disease.

Host: Now, there's yet another study of yours. You've been quite busy with this research, as we've detailed that shows acute histologic chorio independently and directly increases the risk for brain abnormalities seen on magnetic resonance imaging in very preterm infants. So, break down for us what the significance of that is.

Viral Jain, MD: So, this has helped us to predict the risk of the babies while they're still in the NICU. So, cerebral palsy is usually diagnosed at two years of age. That's too late and it's probably too late to start early intervention. So, you want to look at earlier markers of diagnosing cerebral palsy. And the best way to do is look at the imaging.

The traditional imaging, which we do, is just look at the structure. It doesn't tell you the function, the connection and things like that. So therefore, we look for more specific markers, which look as very subtle changes which happens in the brain, which we call the global abnormality score, to look at what these changes are. And if these changes are present, the baby's very high risk likely to get cerebral palsy. So, we showed that chorioamnionitis, which started at birth, continues in these babies, and we can see those changes in the MRI. And these changes which are seen on the MRI also leads to cerebral palsy development. So when you see the changes due to chorion on the MRI in the NICU baby, at about the time of discharge, you can start early intervention on those babies to capture or reduce some of those damages by early intervention.

Host: Gotcha. Now, just a couple other things before we let you go. You were telling me, Doc, before we began the interview that you're with us from your home studio and I see the guitar in the back. Background. You say you're a musician. How do you have time for music with all this research and what kind of music are you into? Tell me about that.

Viral Jain, MD: So, I'm a blues guitar-- I still write a lot of songs for children and stuff. So, I have a reading program. As I said, early intervention is very important. We can't prevent chorio for now, we don't know. I'm working in the lab every day to figure out what medication, but we don't have treatment now. But what we can do is early intervention. So, that includes talking, reading, singing. So, I try to do a lot of advocacy work with music and reading programs. I have a program called NICU Bookworms, which is statewide and nationally, very well known, to increase this reading intervention. And I work with a lot of great musicians such as Zac Brown Band and stuff to write music for babies to help encourage early intervention in babies.

Host: That's awesome. And what impact do you think that music has on babies?

Viral Jain, MD: So, leaving my personal biases aside, there are a lot of really good high quality studies which have shown that music, talking, reading have a profound effect on baby's development. So, because baby's brain, the first two years, even if there is damage, let's say from chorioamnionitis, you can capture a lot of this damage if you stimulate the other areas of the brain. And that could be done with interaction, bonding, talking, singing, and things like that. So, that's what I do when I'm not in my lab.

Host: Yeah, I know from having a two-year-old right now myself, a little over two and a half years old. Even at that age, they're absorbing things all the time in ways that we're not even aware of, right? Learning words and learning things that I know my wife and I did not teach her, and yet she's picking it up from somewhere, right? Like a sponge.

Viral Jain, MD: Yeah. That is truly correct. When they say babies can't hear or talk, for me, it's they can't talk in the language we understand. They truly understand. There have been fMRI studies done, which have clearly shown they have an understanding. It's just the language barrier between us and them. But they're very smart.

Host: Very well put indeed. And finally here, Doctor, in summary, as you continue researching this important topic, what do you hope to achieve to ultimately help the families and babies affected? What are the goals for you here?

Viral Jain, MD: So right now, all we can do is once the damage has happened, what can we do to prevent further damage? So, my work in the lab for, which I have NIH and the American Heart Association grant, is what's the primary culprit of how this chorioamnionitis propagates. We do not have a treatment, so goal is to find what treatment we can give. So when it is just mild, we can stop the progression and it doesn't go into a full-blown chorio and end up delivering the baby preterm. If we can do that, we can prevent a lot of development of organ damages to the lung or to the brain.

Host: Well, folks, we trust you are now more familiar with chorio. Thanks to the great work, both in terms of research and explaining it all for us. Thanks to Dr. Jain, we appreciate the time. Keep up all your great work. It sounds like it's groundbreaking work indeed literally. And thanks so much again.

Viral Jain, MD: Thank you so much for inviting me today.

Host: Absolutely. And for more information about some of Dr. Jain's research that I'm sure he's only given us the tip of the iceberg here on in terms of his explanations, please do check out the links in the show notes now. If you found this podcast insightful, please share it on your social media and explore our podcast library to discover other fascinating topics as well. I'm Joey Wahler. And thanks so much again for being part of the Children's of Alabama PedsCast.

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