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On the cusp of a revolution in the care of newborns

By perfecting the clinical use of non-invasive saliva assays, Dr. Jill Maron, the new director of Pediatrics at Women & Infants Hospital, is opening the doors to personalized preventive health care for infants

Photo courtesy of Dr. Maron

Dr. Jill Maron, director of Pediatrics at Women & Infants Hospital of Rhode Island.

By Richard Asinof
Posted 11/22/21
The new director of Pediatrics at Women & Infants Hospital, Dr. Jill L. Maron, is developing new kinds of non-invasive assays that promise to change the way that health care is delivered for newborns.
What is the role that Women & Infants Hospital will play in the new proposed merged entity of Care New England, Lifespan, and Brown? How will new assays of saliva of newborns exposed to opioids change the way that people with substance use disorder are treated? In proposals for developing the new public health lab for Rhode Island, will there be a place to invest in the development of the biotechnology of saliva assays? Is the Office of the Health Insurance Commissioner ready to adapt its new affordability standards around the support of preventive health care for newborns, the way it has regulated investments in primary care? When talking about preventive health care, when will there be a comprehensive harm reduction database built around the chemical, toxic, and hazardous pollutants in Rhode Island that represent a potential threat to health, including locations, as a component of health care?
The response by Dr. Maron, saying that a baby is not an algorithm, gets to the heart of what is missing from the ongoing analyses of the proposed merger of the health care systems in Rhode Island between Lifespan, Care New England, and Brown.
Too much of our health care delivery system is based upon calculations around the risk management of procedures as a function of cost, not health outcomes. Young people in Rhode Island are awash with unmet behavioral and mental health needs, but providers of such services are often receiving reimbursements that have not been increased, in many cases, for more than 10 years.
There have been reports in the last few days that referrals for Early Intervention programs in the state have been halted, apparently because of a lack of staffing. “We need to be able to pay people more,” one community agency executive told ConvergenceRI.
A news release last week from the R.I. Health Care Association and LeadingAge Rhode Island, representing the state’s 77 nursing homes, claimed that there were currently 1,920 open positions, including 983 openings for CNAs and 447 openings for RNs and LPNs. “The future of long-term care for Rhode Island’s most vulnerable residents stands in the balance,” said John Gage, president of R.I. Health Care Association.
Last week, STAT published a story, “How America’s largest Catholic hospital system is moonlighting as a private equity firm,” written by Rachel Cohrs, detailing how Ascension, which owns more than 140 hospitals, has been running a $1 billion private equity operation, using its wealth “to invest like a Wall Street firm.”

PROVIDENCE – Imagine a simple assay of saliva, taken from a painless, non-invasive procedure from newborns, one that can provide an accurate diagnosis in real time of the baby’s immune responses, identifying biomarkers as an accurate way to target potential infections to inform better care and better treatment.

Then imagine that technology being made available to all caregivers, centralized across all of a hospital’s labs, enabling there to be a read out in a very short time span, so that information can be relayed back in real time to improve care.

And, further, imagine that Rhode Island emerges as the national research center of excellence for an industry cluster built around the technology for such assays, leading to the integration of rapid whole genomic sequencing in neonatal care, positioning the state to become the home of an emerging biotech industry.

That is the promise of the work of Dr. Jill L. Maron, MD, MPH, director of Pediatrics at Woman & Infants Hospital of Rhode Island. Maron is the William and Mary A. Oh/Anna Elsa Zopfi Professorship in Pediatrics for Perinatal Research at Warren Alpert Medical School of Brown University, having succeeded Dr. James Padbury, who recently retired.

Maron is currently directing two separate national clinical studies with National Institutes of Health funding, one looking at saliva assays to diagnose the need for antibiotics, and a second looking at rapid whole genomic sequencing for neonatal care. Maron is also involved with ongoing research looking at the impact of opioids on the brain’s immune system.

Translated, Maron is pursuing medical research at Women & Infants Hospital that promises to transform the way that newborns are cared for, as she explained, “one spit sample at a time.”

The research direction Maron is pursuing, she made clear, was not about financial reward. “It is where we don’t just treat every baby as some algorithm, but rather we have the tools and the technology to understand in the moment what that baby needs.”

Maron, who did her residency at the Warren Alpert Medical School, before spending much of her career at Tufts Medical Center in Boston, where she most recently served as the executive director of the Mother Infant Research Institute and vice chair of Pediatric Research, spoke with passion about her belief that “the status quo is not good enough.”

“I feel very passionately about this,” Maron told ConvergenceRI in a recent interview. “I believe the women of this state, the infants of this state, have and should have every right to have access to the best [clinical] trials that are going to be conducted.”

When you walk in to Women & Infants Hospital to have your baby, Maron said, “You should know, always, that we are not only going to try and deliver the best care, but we are going to advance the care that we give – and that is through research.”

Maron continued: “I have never separated the two; I believe that they go hand in hand. I don’t think the status quo is good enough. And, the only way to improve the status quo is through research. And, while I do not expect that every family has to partake in research, I do feel very passionately that they should be offered the opportunity to do so.”

Here is the ConvergenceRI interview with Dr. Jill L. Maron, M.D. MPH, director of Pediatrics at Women & Infants Hospital, whose research promises to change the way that care is delivered for babies in Rhode Island and across the nation, at a time when the state is trying to better understand the kinds of investments needed to spur growth in the bioscience industry cluster.

ConvergenceRI: Could you describe the kinds of research that you are currently engaged in?
MARON: Sure. For the last 15 years, the bulk of my research has focused on developing salivary diagnostic assays for use in newborns.

I have spent years collecting saliva, analyzing that saliva, and working toward two areas that I have focused on. One is whether I can accurately predict if a baby is infected or not and requires antibiotic therapy.

We do that by monitoring the inflammatory response of the baby. So, we can very readily detect what we call cytokines, or biomarkers, where your body is fighting an infection. And we can detect those and quantify those in literally just a drop of baby saliva.

I am funded by NIH [National Institutes of Health] for a large clinical trial across the country that is looking at that as a potential way to help guide us toward whether we should treat a baby or not treat a baby for infection, because that is one of the things that a neonatologist will struggle with.

Obviously, our patients can’t tell us how they are feeling. They can’t say how they are feeling today. It is very challenging for us to figure out if a baby truly requires antibiotic therapy or not.

ConvergenceRI: You are running a large clinical trial across the country. How many sites are involved with that?
MARON: There are four sites in total that are involved in this particular trial. Brown is one of them, Tufts Medical Center, where I had come from, the University of Florida Gainesville, and then, the Brigham [& Women’s Hospital in Boston] is the lab that runs all the tests, with my partner, Dr. David Walt.

ConvergenceRI: Beyond antibiotics, it would seem that this assay technology could be applied to a lot of different potential analyses. You are looking at bacterial infections if you are looking at antibiotics. But it would seem that there is also the potential to analyze viral infections as well. Is that correct?
MARON: Absolutely. Yes. The key here is that we are not going after the pathogen. We are not trying to detect a specific organism. I am looking for biomarkers that suggest the body is mounting an inflammatory response. So, it could be against anything, as you are pointing out.

It could be a pneumonia. It could be a urinary tract infection. It could be a viral, a fungal, or a bacterial infection. It could be meningitis, it could be a skin abscess; it is not looking for an organism, it is looking for an immune response to an organism.

ConvergenceRI: There is a lot of interesting research going on now, related to the body’s immune system. In particularly, some folks at URI are looking at the brain’s immune system. In terms of potential cross-fertilization, are there lots of people in Rhode Island interested in following what you are doing, given all the work that has begun to be focused on immunology and the different systems in the body?
MARON: That is such a great question. Globally, my work has been working on salivary diagnostic assays. One of the collaborations I have been working on, now that you mention the brain’s immune system, has to do with exactly that.

I have been very fortunate to be training a junior investigator by the name of Dr. Elizabeth Yen. Elizabeth has been using saliva of opioid-exposed babies to understand exactly what you are talking about: How the brain itself could be stimulated to have an inflammatory response.

And, here she also looks at saliva, and she quantifies inflammatory biomarkers with the hypothesis being not that they are infected, but those immune cells of the brain really are often the microglial cells – that they originate from monocytes and, once stimulated, they can induce a cascade in the brain of inflammatory responses.

She has been looking at that exaggerated immune response in opioid-exposed babies. She and others around the country are just beginning to realize that opioid exposure elicits an immune response, and it may very well lead to what we call white matter damage in the neonatal brain. Her work is really exciting and I have been so fortunate to be a part of that for several years now.

So, yes, you are 100 percent right; you are really smart, Richard.

ConvergenceRI: Thank you. I am always surprised by how much or how little I know about things. I have reported on the research of MindImmune; a firm working out of the University of Rhode Island.
MARON: Interesting. I should probably connect with them. Because, I trained Yen how to do the saliva [assays], and we have been working together for several years now, since 2016. And, she has started looking at various aspects of development in the opioid-exposed babies.

There were some very strong animal data coming out, suggesting that these babies, just as you are proposing, that their brain’s immune response was aggravated, it was getting triggered by the opioids, and up-regulating the inflammatory response in the neonatal brains – and that was all done in animals.

And, she has really been one of the first people to take it into the human arena. And really the only reason she can do it is because we utilize saliva as a bio-fluid, and we are able to quantify so easily and safely those biomarkers in babies, which has been always the benefit of saliva, of course.

We don’t hurt a baby to collect saliva. There is an enormous amount of information that can be obtained from the baby’s saliva. And, it gives us that real-time window into what are they doing developmentally or from an infection standpoint today – what is going on today with them.

That has eluded our field, unless you were doing something invasive, like getting blood draws, or collecting other body fluids, and that’s been hard.

ConvergenceRI: I have conducted interviews with Barry Lester [director of the Brown Center for the Study of Children at Risk]. His work has been focused on what seems to be parallel research, but his diagnoses of newborns have been focused on the audio, analyzing the cries of babies.
MARON: Yes, that is correct.

ConvergenceRI: Are you talking to each other? Is that the kind of cross-collaboration or cross-fertilization that can happen?
MARON: Yes, 100 percent. And, as I have taken on this new leadership position, and Barry has been with the [Pediatrics] Department, that is something that I hope could come to fruition, as I get settled and we start to brainstorm together.

ConvergenceRI: Can you talk about your new leadership position?
MARON: I am the new chief of Pediatrics at Women & Infants Hospital.

ConvergenceRI: So, that means that you are replacing Dr. Jim Padbury?
MARON: Correct. I have his former role, yes.

ConvergenceRI: That is impressive. It sounds like they have found a great replacement for him.
MARON: I hope so. I am aiming not to disappoint.

ConvergenceRI: When people talk about the research enterprise in Rhode Island, the research that is being done by Women & Infants often seems to be under the radar screen, despite the fact that the research is on the cutting edge of so many facets of health care innovation.
MARON: I originally trained here at Brown, for my residency. Then I was up to Boston for the last 18 years, where I built my research career.

I have always very much tried to be an innovative, translational scientist, understanding that when I would walk into the NICU as a clinician, the challenges we face were really working with this vulnerable population, and trying to think creatively about how can I develop something that will allow me to better take care of them, without hurting them.

How can I develop techniques so I can give them a voice, because my patients can’t communicate in the traditional ways? We have often been referred to as the “veterinarians” of medicine, because we have just such a unique patient population. I have spent the majority of my professional career trying to do just that.

I have done a wide variety of development of salivary assays. It is not just infection; I have done developmental assays that NIH has also funded. I also run a very large genetic trial across the country in six sites, where we are aiming to integrate rapid whole genomic sequencing into neonatal care to quickly diagnose critically ill neonates back to a genetic disorder.

ConvergenceRI: Can you describe the challenges of this work?
MARON: For me, I really believe that Rhode Island needs to have a change of heart about funding of whole genomic sequencing for all critically ill babies.

We are seeing a lot of movement across the country, where states are now [beginning] to pay for this technology because they view it as so cost-saving – and potentially life-saving – for these babies who are critically ill.

I’ve spent a good amount of time in this space as well. So if I’m not in saliva, I’m in DNA, running clinical trials for NIH.

ConvergenceRI: The current financial mechanisms in the state, and how the state makes investments around health care, and the ways in which health care gets reimbursed, sometimes lack rhyme and reason, in my opinion. There does not seem to be a priority in placing the emphasis on prevention for reduction of long-term medical costs.
MARON: Correct. And, what we are seeing, particularly with genetic sequencing, are states slowly flipping. California was the first to go. They did an internal state study called “Project Baby Bear.”

The [study produced] very compelling data to show that if you can diagnose a baby while they are sitting in the neonatal intensive care unit, it could save hundreds of thousands of dollars in the long run, because you are not doing subsequent testing and biopsies.

For most of these children, it was taking six years to get diagnosed. [With rapid genomic sequencing], they were able to diagnose them in the first few weeks of life with this technology.

In the past month, the state of Michigan has flipped. I have colleagues in New York who are about to walk right into that State House and say: “You need to pay for this.” This is really a no-brainer at this time.

And so, I hope that, as I get settled, and the clinical trial that I am currently conducting comes to fruition, and we are generating all this economic modeling, I can do the same at our own state level in Rhode Island, to say: This is a priority and this makes just flat out common sense, in addition to [producing] huge economic savings.

Because I think so many of our children could benefit from that testing, if done in a very targeted manner. I am not suggesting that we sequence all our babies. But there is subset of babies that are critically ill and we cannot understand why, and these babies could benefit enormously from this type of testing.

ConvergenceRI: I will admit that sometimes I binge on Netflix – and one of the more interesting series I recently watched was an Australian TV show called “Offspring.” Are you familiar with it at all?
MARON: No. What is it?

ConvergenceRI: It follows the story of an obstetrician and her family. There are all these wild and crazy dramas that occur in typical soap opera fashion, but the show revolves around her role in delivering babies. And, after she loses a mother, a patient, she voices her desire to get more involved in research to better understand the parameters of how to improve maternal health.

Which, to me, was a remarkable conversation, because such conversations are certainly not happening on American TV., about supporting the needs of this type of research.
MARON: That is interesting. So this is a documentary?

ConvergenceRI: No. This is seven-season TV production in Australia. It is worth checking out, it is definitely, how would I say, it is classic soap in so many ways.
What I often sense is that in the U.S., there is a lack of conversation to promote the understanding of what is needed on a broader cultural plane around messaging regarding maternal and children’s health. Is that accurate?
MARON: Yes. I think there is a lot of truth to that. And, I think, this is a whole other conversation, Richard. I think there is a huge need to continue important research for maternal and child health, without question.

And, this has often been an area – neglected may be too strong a word – but I think if we look even at the national level of what research gets funded, if we go to NIH, what gets funded are the “big three” that people are afraid of because they might die of them. And that is cardiovascular disease, that is cancer, and that is Alzheimer’s.

When you look at what the NIH portfolio is, there is money going into the Heart, Blood and Lung institute, and [funding for] the Cancer Institute is enormous, compared to [funding for] maternal and child health, which is NICHD [National Institute of Child Health and Human Development].

So, I think there is a huge need for that. These are, of course, “vulnerable” populations. And, with that, comes a lot of responsibility. I use the term “vulnerable” not just because they are children or they are pregnant women but globally, when we talk about minorities and both race and ethnicity, this is really coming to the forefront, because there is an enormous amount of mistrust with research in these populations, and rightly so. We have a very bad history that warrants that mistrust; these are areas that have to be addressed.

But I completely agree with you, if we are talking about this space of Women and Infants Hospital, this is an area of research that desperately needs continued attention, and I would argue substantial funding, on par with some of the other big ones, which are cardiovascular disease, cancer and Alzheimer’s.

ConvergenceRI: I agree with you. Let me switch gears. Jim Padbury was very involved with a collaborative research effort, working with Ed Hawrot at Brown, known as the Advance-CTR [clinical translational research]. Is that something that you have also taken on?
MARON: No. I was not familiar with his work that he had been doing at Brown at this stage. I have only been here about six weeks. I have not connected, other than I have met with the outgoing dean, Dr. Jack Elias, and I am going to be meeting with the incoming dean of the medical school. But that has been my only connection thus far.

ConvergenceRI: In terms of the importance of your research, is there messaging that you think is appropriate to share about how to get that message out?
MARON: There are a few things I would say. I think part of the desire for me to come back to Brown, and I feel very passionately about this, is that I believe the women of this state, the infants of this state, have and should have every right to access to the best trials that are going to be conducted.

And, when you walk in to Women & Infants Hospital to have your baby, you should know, always, that we are not only going to try and deliver the best care, but we are going to advance the care that we give. And that is through research. And, I have never separated the two. I believe that they go hand in hand. I don’t think the status quo is good enough.

In terms of my own research, I very much want to bring diagnostic assays to fruition. So that for a broad range of potential morbidities, or for developmental issues, we can simply screen babies in a very safe way, and have an indication of whether there is pending morbidity, such as an infection, or if there is something more globally, so we can really personalize care for that baby.

I hope by the end of my career that is where we are going, where we don’t just treat every baby as some algorithm, but rather we have the tools and the technology to understand, in the moment, what that baby needs. Whether it is a different approach to feeding, or specific long-term follow up, or antibiotics or no antibiotics.

ConvergenceRI: You said something really interesting in your last response, around caring for babies as differentiated from making decisions based on algorithms. I think that is something that is not well understood, about how much of health care, calculated through different insurance software products, has become basically where folks are making decisions by algorithm and not by the situation.
MARON: Right, right. There are reasons people do that. Whether it is for pay out, for we believe it is for safety, but I think there are always inherent limitations to algorithms. And, babies are not algorithms.

And, while [algorithms] can be used globally as a generalization, they should never become the be-all and end-all for anyone, whether we are talking about what the insurance company should be paid, or how it is that I should treat you.

ConvergenceRI: So, babies are not algorithms. Did I hear that correctly?
MARON: That is correct. They are not algorithms. And, they do have a history of their mothers, because they have been inside for nine months.

We have to remember that. They are alive, and they are stories, they are different. And, we should not treat them all the same, because they are not all the same.

What has been a challenge, of course, is [figuring out] what does a baby need today.

That has really been the focus of the bulk of my entire research career, in asking: What does this baby need today? Whether it is antibiotics or some other intervention to maximize outcomes.

That extends into genetic testing, to understand, does this baby have a genetic disorder or not, and then, how will that guide care, of course, because if you can pick up a genetic disorder, there very well may be a treatment for it, or there may be a redirection of care that could occur, so it is very much diagnosing babies individually, in that moment.

ConvergenceRI: What questions haven’t I asked, should I have asked, that you would like to talk about?
MARON: This just happens to be in the forefront of my mind. Last night I was on a panel for the Museum of Science in Boston, and we were talking about what I was just sort of alluding to, which is personalized medicine, and that is why I was on the panel. And, it revolved a little bit around this genetic testing of newborns.

And, I am very excited about the potential of that, for sure. But I am also very cognizant of the enormous responsibility of what I am saying.

And that is to say, the enormous responsibility of sequencing an infant’s DNA. And, while I am excited about these diagnoses that we are able to make, I am also aware that I am sequencing an individual who did not fully consent; the parents consented. And, that in so doing, there is an enormous amount of burden, because you may uncover things that were unintentional but significant. And, how you handle that for a minor is an enormous responsibility.

I have seen the medical profession look the other way in terms of that responsibility, and I will give you examples. We know that up to one in 10 babies can have false paternity identified on their birth certificate.

The traditional way that the medical profession has handled that is to say nothing, to look away, to pretend that it is not their problem. But it is very much our problem.

One, because, in this day and age, it is very easy to pop on to Ancestry.com or 23andMe, and find out something like this very quickly. Two, it is relevant for medical history. To provide a false medical history is a betrayal for that child. It is not appropriate, and it can have consequences. And, that is an enormous burden, and we have to acknowledge it, and we have to be prepared to handle it, as these technologies unfold.

ConvergenceRI: Great conversation, thank you. The best part of my job is that I am continuing to learn new things.
MARON: Me, too.


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