Daphna Yasova Barbeau, MD

So today in the studio, we are continuing to learn about the Life Course Approach. I have with me Dr. Neal Halfon and Dr. Shirley Russ. I'd like to welcome you both to the program. We are so honored to have your expertise. Offline, Dr. Russ said, “well I'm not a neonatologist.” And I think that's a good thing because I think neonatologists have so much to learn from the rest of our pediatric colleagues about what happens to our babies after they leave the NICU. Sometimes we forget that they're leaving the NICU.

For people who don't know the two of you, Dr. Neal Halfon is a distinguished professor of pediatrics, public health and public policy at UCLA. Dr. Halfon is the founding director of the UCLA Center for Healthier Children, Families and Communities and the director of the Life Course Translational Research Network at UCLA. And Dr. Shirley Russ was a clinical professor of pediatrics at Cedars-Sinai Medical Center in Los Angeles. and is now the Senior Project Scientist for the Life course Translational Research Network. Thank you both for being here today.

I really want to start by highlighting the article that both of you were engaged in as part of this series. It's entitled, “Ensuring Optimal Outcomes for Preterm Infants After NICU Discharge, A Life Course Health Development Approach to High-Risk Infant Follow-Up.” And I told you when we started, we were really going to start from the basics. And so let's really dig down deep. What makes an infant high risk for follow-up?

Neal Halfon

Well, risk is a relative term and it has to do with all the things that affect a child's health, development and wellbeing, not just at a particular point in time, but as they develop and evolve. So those can have to do with issues that go down to the cellular level can make them at risk because of their changes or problems and acid-base metabolism. It can be at an organ level. It could be at a whole organism level, at the whole child level. It could be in terms of their context in the neonatal unit or broader. So I tend to think about risk in terms of the developmental ecosystem that the child is in, and that is an embedded ecosystem with multiple layers. All that needs to be in harmony, if they're not in harmony, then you start to have problems. So that's a relational developmental ecosystem notion of what risk is.

Daphna Yasova Barbeau, MD

Thank you. And Dr. Russ, I know we've spoken a little bit about some of the other societal factors that add to an infant's risk long-term.

Shirley Russ

Yeah, well as Neal said I think it's a really interesting way of thinking about it, this multi-layered and starting at the cellular level, the physiological level even thinking about what we understand now about genetics and epigenetics and about how things like early nurturing care can actually alter our DNA methylation patterns and so on. And if this if these early stages are disrupted or something goes awry, then things can start to go awry in these developmental processes that are invisible at the time. But unless we understand this and unless we're able to intervene and to get processes back on track and better still to optimize them, then we understand that something that may not appear to be a huge risk at this point in time may pose risk for that child's future development as they go through life and they hit the educational system and more demands are made of them and so forth. When we get up to the societal level, we understand that there are many factors that can impinge upon the family as a unit. So things like economic stress, can be severe economic stress. Often both parents find themselves working very long hours. Sometimes they have a premature baby and find that they don't have much family leave eligibility, for example, and this pulls them away from the NICU. And so there is further separation from their child. And so I think one of the things we have thought about a lot in the Translational Network is it's not just the family, it's all these factors going on around the family that can impact their ability, their interactions with their infants. So it's thinking about risk in this broader societal way.

Neal Halfon

And also just to add, it's thinking about it developmentally so that there is not just the cumulative process of the weathering effect of let's say what poverty has on a child or family over time of day after day of sense deprivation which can have cumulative impact. But because of development and things are being initialized and programmed over time. There are certain things that have time-specific effects that are due to the sensitive or critical periods in which some kind of physiological, biochemical, or other kind of programming is going on. And so those things get embedded and can be latent and not really understood and then appear later when that set of processes is being called upon at some other point in time either physiologically or behaviorally or socially. So it's both the cumulative time dependent and also the sensitive period time specific parts of things. And that's oftentimes missed because we miss the importance that development plays. It's not just the exposures, but the developmental exposure.

Daphna Yasova Barbeau, MD

So you're starting to introduce us to the principles of the Life Course. And so I'm learning through this project that the Life Course health development is not a new theory per se. It's something that's been talked about in the community, but I think it might still be relatively new potentially to some neonatologists. And it wasn't until 2018, Dr. Halfon, when you helped develop the seven principles of life course health development specifically for the preterm infant. So if, help us understand what, what does life course health development mean and tell us a little bit about the seven principles.

Neal Halfon

Yeah, well, Life Course Health Development is a framework that integrates insights from multiple disciplines to explain how health trajectories are shaped over an individual's lifetime. And the model emphasizes health is not just the absence of disease, but a continuous developmental process that's influenced by complex interplay of genetic, biological, environmental, and social factors. And for a general physician, I might say that it focuses on health trajectory and how health develops over the lifespan and how it's influenced by early experiences, that there are multiple factors that influence that development, and those critical and sensitive periods end up being really important. I think for a neonatologist, it's really this early developmental focus that's so important and really understanding what that means and how there are so much developmental origins of things that are going to happen later in the child's life. We laid out a series of principles to understand this. These principles aren't linear or hierarchical. They're really like a cloud of things that you need to understand about how health develops.

This a little bit of a sidetrack maybe, but when I was developing this  approach and trying to integrate the science that was emerging in the 1980s and 1990s, the beginning of the DOAD work and David Barker's work in England, some of the work that was most profoundly influential was the neonatal follow-up work and how different the outcomes were, especially from a particular Scottish study, if I remember, in looking at neonates who were either born to poor families or born to higher income families and how their trajectories over time were so radically different. And so that how the social risk over that infant's time actually seemed to outweigh the biological risks. And so that you saw these very different trajectories based on social factors, irrespective of a very similar kind of biological vulnerability that was part of their neonatal cores.

Daphna Yasova Barbeau, MD

I think that's probably especially frustrating for physicians because that feels like sometimes things we don't have any control over. But there are some principles we do have some control over, some contribution to. Maybe you can speak to some of those. I'd actually love if you can start by just outlining the full seven principles.

Neal Halfon