GNS US 2025: Global Nutrition Summit – Approaches to Growth Faltering

Brenda Poindexter, MD

Narrator

Introducing Doctor Brenda Poindexter, Professor of Pediatrics and Marcus Professor in Neonatology at Emory University School of Medicine, and Chief of the Division of Neonatology at the Emory and Pediatric Institute. Doctor Poindexter is an attending physician at Children's Health Care of Atlanta and a nationally recognized leader in neonatal nutrition and clinical research. She has over two decades of experience leading multicenter trials focused on optimizing growth and neurodevelopmental outcomes in preterm infants.

She has authored more than 120 peer-reviewed publications and co-edited several landmark texts, including Nutritional Care of Preterm Infants. Her research has shaped clinical guidelines and feeding protocols used in NICUs worldwide. Doctor Poindexter currently serves on the Board of Directors of the Society for Pediatric Research and the American Pediatric Society, as well as Vice Chair, Protocol Review Subcommittee, National Institute of Child Health and Human Development, Neonatal Research Network.

She is also a trustee for the Pediatric Research Foundation. Please welcome Doctor Poindexter.

Dr Brenda Poindexter:

Thank you so much for being here and I really want to give a heartfelt thanks to Theresa M, Prem and Jessica for inviting me to be a part of this meeting. And wow Ariel, what a fantastic talk, and I am just so impressed, I think, at the fundamental changes to how we provide enteral nutrition that he and his team have made, so really a privilege to share this session with you.

I want to give a special thanks to Barbara Cormack and Frank Bloomfield, who were my coauthors on the chapter on growth faltering, in the last edition of Nutritional Care of Preterm Infants. And that's where a lot of this information can also be found.

So, these are the objectives, and I think there have been changes in how we define growth faltering, and I want to try to describe some strategies to prevent that. A lot of the enteral strategies, Doctor Sallis already kind of walked us through. And then we'll talk briefly about some of the causes of growth faltering and some intervention strategies.

Teresa also asked me to talk about post-discharge management, and I would say that is probably one of the areas where we need more studies the most, because there really isn't great evidence for some of the practices, once the baby leaves the NICU.

So, I feel like I'm preaching to the choir to say that nutrition is a modifiable factor that can really mediate a lot of morbidities of preterm birth, including many that are associated with poor growth.

One of the least helpful recommendations, I think, of all time is the statement by the AAP that our goal is to provide nutrients to approximate the rate of growth and composition of weight gain for a normal fetus, and to maintain normal concentrations of blood and tissue nutrients. I don't know what in the world that means or how we would actually do that or measure it. So not very helpful. I think another tricky goal is optimizing neurodevelopment and long-term health outcomes. I think Ariel showed us that sometimes there are things we can do to improve growth, but it doesn't always translate to improved neurodevelopment. And another thing is that these babies, as you all know, have so many other comorbidities of preterm birth that also impact neurodevelopment. And so, I think that that's going to be challenging to tease out.

So, these are recommendations for the target growth rate, based on weight in grams per kilo per day. And I think that guidelines like this are great, except even when we meticulously follow all of the recommendations for how to provide nutritional support, sometimes we can't achieve these.

Another issue is that I think we get so focused on weight gain that we forget about the importance of length and head growth. So, I really think that instead of, you know, when we're making rounds in the unit or even when we're looking at various studies of nutritional interventions, I think looking at that trajectory of growth is so very important and isn't always reflected in how many grams per kilo the baby gains.

So how do we define growth faltering? And I sort of want you to think about two different periods, one being the prenatal course, or when the fetus is still in the womb, and then the postnatal growth. And so really we talk about small for gestational age, which is really just a statistical definition where you look at a particular anthropometric parameter and you say it falls below a particular cutoff, usually the 10th or the third percentile, whereas fetal growth restriction really is talking about a fetus that at one point was growing at a certain rate and then you have pathological slowing, that could be due to a maternal illness like pre-eclampsia, could be due to twin gestation or other things. And then postnatally, for the longest time, we've sort of relied on this definition of extrauterine growth failure or growth faltering, as being a weight less than the 10th percentile at 36 weeks, corrected age. And I think with very good reason many experts are now calling these terms misnomers. And I think that a big part of that is because again, it's focused on weight. Some of our growth curves really don't take into account that physiologic weight loss that happens in the first week to ten days. And because we're not sure that these definitions always predict the outcomes that we're most interested in.

So, again, the common definitions I think are problematic. And then I'm going to kind of go over the differences between intrauterine and postnatal growth curves and why they also add some challenge to the mix. But really that physiologic weight loss that occurs from extracellular fluid contraction is equivalent to a decrease in a weight z-score of approximately 0.8. Other studies have shown, especially for extremely low birth weight infants, that there can be an even greater decline in the first few weeks.

So, this is an example of an intrauterine growth curve, that you may have in your electronic medical record. Hopefully you're using a sex specific curve that accounts for prematurity. This one is the second-generation Fenton curve and you can see the weight, length and head circumference, and the way that these curves were constructed really is by taking the measurements at birth for a baby born at the particular gestational age. And so, the inherent challenge is that something went awry with that pregnancy that resulted in preterm birth.

Others, this is work done many years ago by our dear friend and one of my dearest mentors, Doctor Rich Ehrenkranz. And what he did is to take a population of babies in the neonatal research network and basically plot them on the intrauterine growth curves. Again, these were several decades ago, but the point was that at that time, some babies weren't regaining birth weight for two to three weeks, and by the end of the NICU stay, virtually all were less than the 10th percentile.

So, some people have proposed saying – well, maybe the standard is what's wrong, and maybe we should use some of these postnatal growth curves to measure how successful we're being as we care for these babies. And I would argue that, again, these are sort of inherently flawed as well, because maybe we're not doing a great job, and we certainly shouldn't be the gold standard if so many of our babies are experiencing growth faltering.

I think one of the really exciting things is the most recent study that Tanis Fenton has put out that really describes what she's calling a third generation of growth curves. And this systematic review and meta-analysis includes 4.8 million births, with 175,000 less than 30 weeks gestational age. And I think that what she did was so brilliant because she took and only included infants that had normal fetal growth. And so, when you look at the growth velocities across percentiles, it fits much better than when you switch to the WHO curves, and the birth weight curves are more similar to fetal U.S. estimates. And so, I think that, I'm hoping that these will become incorporated into our electronic medical records so that we can use them sort of as a reference, as we're providing care for these babies in the NICU.

Okay. So, I'll give you a heads up, this is where your audience poll question is going to come in. And so, I want to give you two different babies, both born at 24 weeks gestation. Baby A starts out at 580g and baby B starts out at 720g. And you can see their weight percentiles at birth, one week and at 36 weeks, and also the corresponding z-score.

And so my question for you is pretty simple – which of these babies are you going to be most worried about? Is it baby A, baby B, or a third option would be I'm equally concerned about both of them. So, I'll give you a minute to look at that.

Okay, great. I would agree with those of you that are saying baby B, I wouldn't quibble with those of you that are concerned about both.

And I think that the reason that I'm more concerned about baby B is that, if you look at baby A, they really are having that decrease in the weight z-score of about 0.8. And then from one week to 36 weeks, they're actually following along a pretty steady trajectory. But baby B has a greater than 0.8 decrease. And really then from one week to 36 weeks, something else must have happened because they've had further faltering off of that trajectory.

So, what do we do to prevent growth faltering? Well, really, I want to talk a little bit about early parenteral and enteral nutrition, early fortification of human milk, both themes that Ariel talked about so well. And then really thinking about that transition between parenteral and enteral nutrition and the importance of standardized feeding protocols. I think Ariel said it so well, you know, not everyone who is practicing neonatology has nutrition as their primary focus, and especially if they're more worried about lung disease or other things, they're looking for an excuse to not want to advance feedings because they're afraid that something bad might happen, like NEC.

This is a super old slide, but I found that especially with our trainees, they can't even remember a time that we didn't start amino acids immediately after birth. When I was a trainee, and now I'm giving away my age, we would keep babies on glucose sometimes for the whole first week of life. And so, this is work that I did as a fellow, in Indianapolis with Scott Denne. And it really just shows you what protein accretion would have been for the fetus in utero, in green. And then what would happen in terms of protein loss, if the baby was receiving glucose alone. And then kind of showing you where that balance would be with one versus three grams. And so this is really some of the foundational, kind of, why we use early, kind of what we call vanilla or starter TPN, is just to give enough amino acids to sort of mitigate that protein loss.

We've had lots of observational studies over the years that show that some of those early protein and energy deficits, can be really difficult to recover from and contribute to poor growth outcomes. I think there have been a variety of observational studies that have shown differences in terms of, does this positive protein and energy balance actually lead to improved neurodevelopment with things like the Bayley scores?

So I kind of already talked about, you know, early parenteral nutrition. I think that another thing that people sometimes will do is as they're advancing enteral feedings, they'll simultaneously start reducing the parenteral nutrition that they're giving. And especially if you're not doing early fortification, there can then be greater gaps in what you're intending to deliver and what actually reaches the baby.

I wanted to talk a little bit about a more recent, randomized trial that was done in New Zealand and Australia. Barbara Cormack led the ProVIDe Trial. And they randomized babies either to standard nutrition or giving one gram per kilo of additional amino acids, for the first five days. And their primary outcome was survival free from neurodevelopmental impairment. And they looked at the babies at two years corrected age. So, their primary outcome measure, they did not find a difference in neurodevelopment and actually some suggestion of concern for harm. But then they did a cohort analysis of the nutritional intake over the first four weeks and found that that really again, similar to older observational studies, was correlated with growth at both four weeks and 36 weeks corrected age.

I think, along with what Ariel talked about too – protein is more strongly correlated with growth than other macronutrients. They saw that length faltering can continue up to 36 weeks. And again, I think this is something that not all units do well in terms of consistently measuring length, with an appropriate length board. Then they also found some pretty big differences in outcomes amongst sites. And I think that this also really is a good indication that we need standardized feeding protocols across sites so that we can enhance our practice of providing nutrition.

So, I'm really going to skip over this because I think that Doctor Salas just gave us a masterclass on how important early enteral nutrition is. But the one thing that, I think gets overlooked sometimes is the inherent differences between mother’s own milk and donor milk. And so, what this slide shows in green is sort of the protein composition of mother’s own milk over time. And so, colostrum in early milk is much higher in protein, early on, and higher than donor milk. I think that might be one of the things in one of your questions for later. And that declines over time, but if you look at the package instructions for any of the commercial human milk fortifiers, there's sort of an assumption made about what that base protein content is of the milk that you're adding the fortifier to. So, if you are fortifying and have a baby that's receiving mother’s milk and they’re somewhere between two and four weeks of age, you're probably coming pretty close to what the package is telling you that you're delivering in terms of total protein.

But we all know that these babies stay in our NICUs for far longer than two to four weeks. And so, I kind of think about the tail end of that curve and think about how much time, if we're not adjusting our strategy of how we fortify, we probably are giving much less protein than we intended. And then, you know, if you're using donor milk as the base, some of those gaps are just magnified. And I really feel that we should have different fortification strategies depending on if the baby's predominantly receiving mother's milk or donor milk.

This is a hypothetical kind of exercise, looking at the transition from parenteral to enteral nutrition. I won't go over all of this, but basically, if you are, you know, tapering your parenteral intake, which is shown in the black bars and you're waiting to add fortifier until relatively late, in this sort of hypothetical scenario, you're only achieving a little more than three grams per kilo. But if you if you take a slower approach to tapering your intravenous amino acids and you start fortifier early, then you're delivering much higher protein. And so, I think that it's a period of vulnerability where we think we're doing a better job than maybe we are, if we're not really carefully looking at how much is the baby getting in parenteral and enteral nutrition.

So standardized feeding protocols, I think incorporate both consensus and evidence-based strategies. And I think that, again, Ariel hit on this, like you can have a protocol, but if people in the unit are afraid to use it or if you don't have buy-in then it's not going to be helpful. But they really do mediate the impact of perceived severity of illness on decisions related to nutritional support. And they have shown to improve outcomes following implementation with the most impressive being a reduction in NEC. And I think it's one of those things that, you know, it's really not necessarily the individual components of your feeding protocol, but the fact that you have one that people are willing to adhere to, that results in a reduction in NEC.

So there are many causes of growth faltering. I think it's important to sort of think about them, because that will inform the approach that you take in terms of how to address it. But there are many comorbidities of prematurity that are associated with poor growth outcomes, such as NEC, intestinal perforation, BPD or even severe ROP. And then the way that we take care of these babies in terms of fluid restriction, if they have a PDA or diuretics, systemic steroids, all can have a profound impact on our nutritional support.

Babies may have inadequate protein intake, they may have sodium depletion even while maintaining a normal serum sodium. And this is particularly true in babies that have high losses through an ostomy. I think we're learning more about the role of zinc deficiency, fat and carbohydrate malabsorption, anemia, and even increased energy requirements in babies with congenital heart disease with a left to right shunt.

So, I think that, you know, understanding that we can't wait until 36 weeks to decide if a baby has faltering growth is really important. I think weight, I prefer to have it measured daily, but a minimum of two to three times a week, length, with the length board, and head circumference, and we know that that has an important prediction for long term outcomes. Thinking about not just, not just what those absolute measurements are, but how that relates to a z-score, to really look at change over time and keeping in mind that if you are greater than 2 in your z-score, that that's associated with severe malnutrition. Mid-arm circumference, which certainly correlates without adiposity but should not be used in isolation. And then, body mass index, there are curves for that. And also the PeaPod, which I think at this point is really, probably only useful in a research context. There's been a lot of focus on sodium supplementation, including trials in preterm babies, to have early sodium supplementation to improve weight gain. There's a recent study that was Jeff Segar and Greg Sokol, looking at an algorithm to monitor urine sodium concentrations. We do this pretty strictly in babies with any kind of intestinal resection. And if the weekly urine sodium is low and especially less than 20, that's usually an early indicator that we're not meeting their total body sodium needs.

I think the usefulness, in the very preterm baby, we need a little more information, but I think it can be a useful tool if you're seeing flattening of growth and the urine sodium is very low, I think that's usually a good indication that we need to add more.

Some of the intervention strategies can be to use higher enteral volumes, giving additional human milk fortifier, especially thinking about if you're at that time where the underlying protein concentration in the milk has declined, adding liquid protein, especially if the babies are receiving donor milk and then sometimes, you know, increasing caloric density and maybe thinking about switching from donor milk to preterm formula if your growth is really abysmal.

Post-discharge nutrition, tremendous variation in practices. I think there's a lot of ways that we can optimize things for when babies are going home, but it really takes an understanding of what are mom's goals for breastfeeding and trying to really maximize that. So, if we have a preterm baby who is doing well at the breast, I actually might increase caloric density for those few feedings that maybe they're taking by bottle or gavage. And I think that it's, you know, important to have follow up. I also think that we're sending some of these babies out into the community with pediatricians who haven't cared for them in their NICU stay and may not be as familiar with the importance of ongoing ideal growth. And so, I think we have to do, also, a better job of educating some of the community pediatricians about what our goals are. I've found a great way to do that is to, you know, throughout their NICU stay, to kind of go over the growth curves with mom so they know what I'm looking for, and they don't go to the pediatrician and have one good weight check and then, you know, have all of the extra fortification stopped.

So, the European societies kind of talk about the use of fortification or kind of transitional formulas for babies, especially those that are at higher risk for long term growth failure. The AAP supports discharge formulas, I think the recommendation there is 40 to 52 weeks, with the strongest evidence being in those babies that were small for gestational age. But again, I think this is an area where we need a lot more data and studies.

So I'll wrap up just by giving you some key messages. Growth faltering is a change in a growth trajectory, not an isolated position on a growth curve at any point in time. And although most of our VLBW and ELBW infants may be appropriate for gestational age at birth, postnatal growth faltering does remain a common complication of pre-term birth. A decrease in 0.8 standard deviation in the weight z-score over the first few weeks is likely physiologic, and although weight gain is important and simple to measure, proportional gains in linear growth and head circumference are also essential to optimize outcomes. Prevention is ideal, but when growth faltering does occur, prompt recognition, thinking about the contributing factors and appropriately intervening, is needed. I think definitions of growth faltering require validation in future studies to sort of think about what pattern of growth should we target and how can we best achieve not only improved growth outcomes, but also, neurodevelopmental and other long-term outcomes.

Thank you very much.